Variables pronósticas de pacientes con melanomas gruesos. Análisis de 362 casos / Prognostic variables in patients with thick melanomas. Analysis of 362 cases

Resumen Antecedentes: Los estudios sobre factores pronóstico de melanoma están basados en poblaciones caucásicas, con predominio de melanomas delgados (Breslow < 3 mm). Los pacientes mexicanos muestran predominio de melanomas gruesos (Breslow ≥ 3 mm). Objetivo: Identificar factores asociados al pronóstico de pacientes con melanomas gruesos. Material y métodos: Se analizó la influencia pronóstica de factores clinicopatológicos en 362 melanomas gruesos. Resultados: La mediana de Breslow fue de 7 mm, 271 (74.9 %) pacientes tuvieron melanoma acral y 49 (13.5 %) melanoma nodular. El 56.6 % de los pacientes se encontró en etapa clínica [EC] III), 269 (74.3 %) tenía ulceración y 15 (4.1 %) márgenes positivos. Las variables asociadas con menor supervivencia global [SG] fueron la EC (p < 0.001), Breslow (p = 0.044), ulceración (p = 0.004), mitosis (p < 0.001) y margen < 2 cm (p < 0.001) . En el análisis multivariante los factores que influyen en SG fueron la EC, mitosis y el margen quirúrgico. Conclusiones: En pacientes con melanomas gruesos la SG es influida por un margen positive, mitosis y EC.

Abstract Background: Studies on prognostic factors in melanoma are based on Caucasian populations, with a predominance of thin melanomas (Breslow <3 mm). Mexican patients show a predominance of thick melanomas (Breslow ≥ 3 mm). Objective: To identify factors associated with the prognosis of patients with thick melanomas. Material and methods: The prognostic influence of clinicopathological factors was analyzed in 362 thick melanomas. Results: The Breslow median was 7 mm, 271 (74.9 %) patients had acral melanoma and 49 (13.5 %) nodular melanoma. The 56.6 % of patients were found in clinical stage [CS] III), 269 (74.3 %) had ulceration, and 15 (4.1 %) had positive margins. The variables associated with lower overall survival [OS] were CS (p < 0.001), Breslow (p = 0.044), ulceration (p = 0.004), mitosis (p < 0.001) and margin < 2 cm (p < 0.001). In the multivariate analysis, the factors influencing OS were CD, mitosis, and the surgical margin. Conclusions: In patients with thick melanomas, OS is influenced by a positive margin, mitosis and CS.

Características do melanoma em idosos / Characteristics of melanoma in the elderly

RESUMO Objetivo: Avaliar características do melanoma em idosos. Método: Pesquisa retrospectiva mediante revisão de prontuários de idosos diagnosticados com melanoma cutâneo primário, no período de 2013 a 2017, atendidos no Hospital Erasto Gaertner, em Curitiba-Paraná. Resultados: Amostra com 139 pacientes, mulheres (52,5%), média de 70,3 anos de idade, com lesão em membro superior ou membro inferior (32,3%) e cabeça (24,4%), sinais de ulceração (33,8%) e classificação em tipo histológico nodular (29,5%), extensivo superficial (27,3%) e acral (11,5%). Média do índice de Breslow de 3,7 mm. Metástases ocorreram em 33% dos pacientes, para linfonodos (36%) e sistema nervoso central (20%). Pesquisa do linfonodo sentinela foi realizada em 41,7% e tratamento cirúrgico isolado em 70% dos casos. Houve recidiva em 34,5% pacientes e 17,9% evoluíram com óbito. Esses achados apontam características prognósticas sombrias relacionadas ao diagnóstico e tratamento tardio da neoplasia. Conclusões: Melanoma em membros e cabeça, índice de Breslow intermediário, metastático para linfonodos e sistema nervoso central, recidiva e tem desfecho fatal. Há necessidade de direcionar estratégias para melhor abordagem da doença em idosos, como prevenção, detecção precoce e oferta de tratamento uniforme e adequado.

ABSTRACT Objective: This study evaluates melanoma characteristics in the elderly. Methods: A retrospective descriptive analytical study was carried out by reviewing the medical records of patients aged 60 years or older, diagnosed with primary cutaneous melanoma, and treated at Hospital Erasto Gaertner, Curitiba, Paraná, from 2013 to 2017. Results: We studied 139 patients aged 60-98 years (average, 70.3 years) and found melanoma to be more common in women (52.5%) than in men. Lesions mainly affected the limbs (32.3%) and head (24.4%), showed signs of ulceration (33.8%), and could be classified into the nodular histological (29%), extensive superficial (27%), and acral (12%) types. The average Breslow index was 1.2 mm. Metastasis occurred in 33% of the patients and mainly affected lymph nodes (36%) and the central nervous system (CNS, 20%). The first procedure conducted in 79% of the cases was surgical resection. Sentinel node mapping was carried out in 41.7% of the cases, and surgical treatment alone was indicated in 70% of the patients. The disease recurred in 34.5% of the patients, and 17.9% succumbed to the disease. These results indicate that the elderly have poorer prognosis when cancer treatment is delayed. Conclusion: Melanoma of the limbs and head, intermediate Breslow index, metastatic lymph node and CNS metastases, and relapse result in fatal outcomes. Direct strategies, such as prevention and early detection, as well as uniform and adequate treatment, are needed to improve disease management in the elderly.

Histogenetic categorization of atypical melanocytic tumor of uncertain biological malignant potential

Abstract: Several reports have demonstrated difficulties and lack of agreement in the histopathological diagnosis of particular melanocytic lesions, with problems in their management. A histogenetic approach to the study of these lesions originated the following classification: 1. superficial atypical proliferation significance; 2. melanocytic tumor of uncertain potential; 3. pigmented epithelioid melanocitoma of uncertain potential; 4. microinvasive radial growth phase of uncertain potential. The terminology remains controversial, reflecting the uncertainty of the diagnosis and the biological potential of these atypical melanocytic lesions.

What does the 4th edition of the World Health Organization Classification of Head and Neck Tumors (2017) bring new about mucosal melanomas?

Abstract: The recently published 4th Edition of the World Health Organization Classification of Head and Neck Tumors addresses the most relevant and updated aspects of tumor biology, including clinical presentation, histopathology, immunohistochemistry, and prognosis of head and neck tumors. The objective of the present study is to compare these updates to the 3rd edition of that book with regard to mucosal melanomas and to highlight the potential factors that differ those tumors from cutaneous melanomas. We observed progress in the understanding of oral and sinonasal mucosal melanomas, which also present themselves, in the molecular scope, differently form cutaneous melanomas.

Melanoma maligno metatastásico: reporte de caso / Metastasic malignament melanoma a case report

El Melanoma Maligno es una de las neoplasias más agresivas, siendo responsable del 90% de las muertes por cáncer de piel; Su incidencia fue incrementándose durante las últimas décadas a nivel mundial. La progresión de la enfermedad puede presentarse en forma de recurrencia local, por diseminación linfática hacia los ganglios regionales, o por metástasis hematógena a sitios distantes: piel, órganos y hueso entre otros. Las metástasis regionales y a distancia, se presentan aproximadamente en 10% de los pacientes con melanoma, al momento del diagnóstico, conllevando peor pronóstico. La supervivencia a 5 y 10 años en pacientes con metástasis a distancia es de 12%-15% y 8%, respectivamente. Se presenta el caso de un paciente que rechaza tratamiento inicial de ablación de lesión primaria, presentándose múltiples metástasis y desenlace fatal.

The malignant melanoma is one of the most aggressive neoplasias, being responsible for 90% of the deaths due to skin cancer; its incidence was increasing during the last decades worldwide. The progression of the disease can occur in the form of local recurrence, by lymphatic dissemination to the regional ganglia, or by hematogenous metastasis to distant sites: skin, organs and bone among others. Regional and distant metastasis occurs in approximately 10% of patients with melanoma at the time of diagnosis, leading to a worse prognosis. The 5-year and 10-year survival in patients with distant metastasis is 12% - 15% and 8%, respectively. The case of a patient who refuses initial treatment of primary lesion is presented, presenting multiple metastasis and fatal outcome.

Ação de metabólitos da via das triptaminas em linhagens de melanomas / Action of tryptamines pathway metabolites in melanoma strains

O triptofano (Trp) é essencial para muitos processos fisiológicos e seu metabolismo apresenta-se alterado em doenças como no câncer. O Trp é degradado por três vias: via das quinureninas; via serotonérgica e via das triptaminas. A primeira está envolvida com a tolerância e o imune escape de células tumorais, já a segunda leva a produção de serotonina e melatonina, com uma diversidade de funções biológicas e que possuem atividades antitumorais reconhecidas. A terceira rota é a menos estudada e a função dos compostos sintetizados ainda é desconhecida. Trabalhos do grupo mostram que a via das triptaminas é ativa em melanomas e que triptamina (TRY) e dimetiltriptamina (DMT), metabólitos produzidos por esta via, também possuem atividade antitumoral. Nosso objetivo é avançar sobre a compreensão de como esta via afeta o metabolismo e crescimento tumoral. Para tanto, estudamos mais detalhadamente a via em linhagens de melanoma. A adição de TRY e DMT nas culturas modificou a produção de compostos das outras rotas de metabolização do Trp. Além disso, TRY e DMT afetaram a invasividade das células tumorais e TRY aumentou a atividade citotóxica de células mononucleares frente a melanomas. Observamos que apesar dos efeitos biológicos da via das quinureninas estar amplamente relacionado a ligação dos metabólitos no receptor de aril hidrocarbonetos, para a via das triptaminas o receptor parece não estar associado com a atividade antitumoral descrita. Nossos resultados apontam para a importância da via das triptaminas na dinâmica tumoral e a necessidade de estudos mais amplos relacionados ao metabolismo do Trp

Tryptophan (Trp) is essential for many physiological processes and its metabolism is modified in several diseases such as in cancer. TRP is broken down into three pathways: kynurenine path, serotonergic path and tryptamine path. The first is involved in tolerance and immune escape of cancer cells, while the second leads to the production of serotonin and melatonin, which have a variety of biological functions and recognized antitumor activity. The third route is the least studied and the biological function of the synthesized compounds is still unknown. Our group shows that tryptamine path is active in melanomas and tryptamine (TRY) and dimethyltryptamine (DMT), metabolites produced by this route, also have antitumor activity. Our goal is make progress on understanding how tryptamine route affects metabolism and tumor growth. Therefore, we studied in detail this pathway in melanoma cell lines. The addition of TRY and DMT into the cultures leds the production of metabolites of other Trp routes. Moreover, TRY and DMT affect the invasiveness of tumor cells and TRY increased antitumor activity of the immune system against melanomas. We observed that despite biological effects of kynurenine path be largely related to metabolites binding aryl hydrocarbon receptor, for tryptamine pathway the receptor seems not to be associated with the described antitumor activity. Our results point the importance of tryptamine pathway in tumor dynamics and the need for broader studies related to Trp metabolism

Linfogammagrafía con SPECT/CT en neoplasias cutáneas de cabeza y cuello / Lymphogammagraphy with SPECT/CT in head and neck cutaneous neoplasms

Las neoplasias cutáneas son un motivo de consulta cada día mayor; especialmente, en las regiones del trópico. Para los profesionales que atienden a pacientes con este tipo de patologías, resulta de vital importancia tener claro el manejo de ellas; sobre todo, el melanoma y el carcinoma escamocelular de piel de cabeza y cuello. No solo se debe tratar el sitio primario, sino también los relevos ganglionares que podrían estar afectados, dependiendo de los factores de riesgo de la enfermedad. Como no está claro el uso de intervenciones conservadoras para tratar los ganglios del cuello en estos pacientes, ha surgido en el Instituto Nacional de Cancerología (INC) la necesidad de implementar el uso de la linfogammagrafía con tomografía computarizada de emisión de fotón único más tomografía computada (SPECT/CT), para definir cuáles grupos ganglionares del cuello deben ser retirados. Con el fin de aclarar tópicos de esta técnica, se revisa el tema.

According to medical statistics, the frequency of cutaneous neoplasms is on the rise, particularly in tropical regions. It is highly important for physicians who treat these pathologies to have extensive knowledge on their control, especially for melanoma and head and neck squamous cell carcinoma. Not only should the primary site be treated, but so too should the relay lymph nodes, since these could be affected, depending upon the risk factors of the disease. Due to the fact that no clear conclusions exist on the effects of using conservative interventions to treat neck ganglia in these patients, the National Cancer Institute of Colombia (INC) has initiated the use of lymphogammagraphy with computed tomography single photon emission plus computed tomography (SPECT/CT) to define which neck nodal groups should be removed. Aspects of this topic are reviewed below.

Melanoma tipo animal: relato de dois casos / Animal type melanoma: a report of two cases

Dificuldade potencial no diagnóstico histológico de melanomas é a dificuldade em reconhecer variantes pouco frequentes de melanoma. Entre elas, as mais desafiantes incluem exemplos de melanoma desmoplásico, melanoma nevoide, o chamado "melanoma de desvio mínimo", melanomas com proeminente síntese de pigmento ou "melanoma tipo animal" e o nevo azul maligno. Os autores descrevem dois casos de melanoma tipo animal e discute-se a importância do diagnóstico diferencial clinico-histopatológico nesses casos.

A potential diagnostic pitfall in the histological assessment of melanomas is the difficulty in recognizing unusual melanoma variants. Among them, the most challenging examples comprise desmoplastic melanomas, nevoid melanomas, the so-called minimal-deviation melanoma, melanomas with prominent pigment synthesis or animal-type melanoma, and the malignant blue nevus. Two cases of animal type melanoma are reported and the importance of clinical-histopathological differential diagnosis is discussed.

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.

Estudo clínico dos nevos melanocíticos congênitos na criança e no adolescente / Clinical study of the congenital melanocytic naevi in the child and adolescent

FUNDAMENTOS: a classificação dos nevos melanocíticos congênitos (NMC) e a magnitude do risco de transformação em melanoma são ainda polêmicos.OBJETIVOS: Analisar o perfil dos NMC em crianças e adolescentes no IPPMG-UFRJ segundo sexo, cor, idade, tipo clínico, localização e evolução. MATERIAL E MÉTODOS: Estudo longitudinal de coorte retrospectivo e prospectivo de 1994 a 2007; amostrade demanda espontânea e referida.RESULTADOS: 30 crianças e 30 adolescentes apresentaram 74 NMC: 60,8% (pequenos), 27% (médios),5,4% (grandes) e 6,7% (gigantes), sendo que 45,9% no sexo masculino e 54% no sexo feminino e 45,9% em brancos e 54,% em não brancos. Sexo e cor não influenciaram o tipo clínico. Dentre os pequenos e médios, 27,1% apresentaram-se no tórax e 23% na cabeça e pescoço; os grandes e gigantes no pólo cefálico, região cervical, linha média posterior e membros; 28,3% foram seguidos por mais de 10 anos,47,3% entre três e nove anos e 24,3% por tempo inferior a três anos. Os NMC pequenos e médios se mantiveram inalterados; um grande e dois gigantes mostraram clareamento; nenhum caso desenvolveu melanoma. CONCLUSÃO: distribuição homogênea entre brancos/não brancos e sexo masculino/ feminino. O sexo e a cor não tiveram relação com o tipo clínico; os NMC pequenos predominaram com localização preferencial no tronco.

BACKGROUND: The classification of the congenital melanocytic nevus (CMN) and the magnitude of the risk of transformation into melanoma are still controversal. OBJECTIVE: To analyse the profile of the CMN in the child and teenager at IPPMG-UFRJ according to sex, skin colour, age, clinical type, locations and evolution. METHODS: Longitudinal study of retrospective and prospective cohort from 1994 to 2007. Aleatoric sample from spontaneous or referal demand. Results: 30 children and 30 teenagers showed 74 nevi: 60,8% (small), 27% (medium), 5,4% (large) and 6,7% (giant); from these, 45,9% were in the male sex and 54% in the female sex. There were 45,9% in whiteand 54% in non-white. Sex and skin colour didn’t influence the clinical type. Among the small and medium nevi, 27,1% were located in the trunk, 23% in the head and neck; the large and giant ones in the head, neck, back and limbs; 28,3% were attended for more than 10 years, 47,3% between three and nine years and 24,4% for a time below three years; the small and medium CMN kept unchanged. The fading of the lesion was observed in one large and in two giant CMN. No cases of melanoma were observed. CONCLUSION: An homogeneous distribution among white/non white and male/female; the sex and the ethnic group did not influence the clinical type; the small CMN was the most frequent clinical type mainly in the trunk.

Actualización de los factores pronósticos del melanoma maligno / Prognostic factors for malignant melanoma: updates

Introducción: En el año 2002, el American Joint Committee of Cancer (AJCC) propuso un nuevo sistema de etapificación para el MM a partir de factores pronósticos independientes. Se ha visto que existen otros factores que no fueron analizados que podrían modificar el pronóstico. Método: Se revisaron en la literatura los factores pronósticos clínicos e histopatológicos del melanoma descritos hasta la fecha. Se consideraron los niveles de evidencia y la aplicación clínica. Resultados: Según los criterios del AJCC, para el estadio I y II, los factores pronósticos son el índice de Breslow, nivel de Clark para el grupo <1mm y la presencia de ulceración. Para el estadio III, importa el número de linfonodos comprometidos (1vs 2-3 vs >3), enfermedad micro o macrometastásica, metástasis en tránsito y satélites. Para el estadio IV, el sitio de metástasis y los valores de LDH. Se ha visto que el sexo masculino, edad avanzada y tumores localizados en extremidades son factores pronósticos adversos. A pesar que aún no se recomienda el uso rutinario del índice mitótico, se ha postulado que sería un factor pronóstico más importante que la ulceración. La presencia de regresión e invasión linfovascular serían otros factores histopatológicos de mal pronóstico. Los mecanismos moleculares de la tumorogénesis pueden mejorar la predicción del pronóstico del paciente.Conclusión: Si bien el sistema de etapificación actual provee una excelente herramienta para determinar un pronóstico general, el uso de factores pronósticos recientemente identificados permitirá realizar un pronóstico más preciso y más individualizado.

Introduction: In 2002, the American Joint Committee of Cancer (AJCC) proposed a new system for staging MM from independent prognostic factors. It appears that there are other factors that were not analyzed that could change prognosis. Method: We reviewed the literature on the clinical and pathological prognostic factors of melanoma described so far. Evidence levels and clinical application were considered.Results: According to the AJCC, the criteria for stage I and II prognostic factors are: Breslow index, Clark level for the < 1mm group, and the presence of ulceration. For stage III, the number of adenopathies involved (1vs 2-3 vs.> 3), micro or macro metastatic disease, metastases in transit and satellites are important. For stage IV, the site of metastasis and values of LDH. Adverse prognostic factors appear to be: male, elderly and having tumors in the extremities. Although the routine use of mitotic index has not been recommended yet, it has been postulated that this may be a prognostic factor more than important ulceration. The presence of regression and linfovascular invasion are other histopathological elements of poor prognosis. The molecular mechanisms of tumor formation can make prognosis more precise and individualized. Conclusion: Although the current staging system provides an excellent tool to determine an overall prognosis, the use of newly identified prognostic factors will permit a more accurate and more individualized prognosis.

Melanoma maligno en cavidad bucal en una mujer de Tucumán, Argentina / Malignant melanoma of the oral cavity in a woman from Tucuman, Argentina

El melanoma es un cáncer de origen melanocítico extremadamente raro, de pronóstico grave con una pobre sobrevida a los cinco años. El objetivo del presente trabajo es comunicar un caso clínico de melanoma de la cavidad bucal correspondiente a una mujer de 75 años de edad, en la cuál se estudiaron los niveles séricos de las enzimas lisosomales, Fosfatasa Ácida (FA), Hexosaminidasa (Hex), Beta Galactosidasa ( -Gal) y el Antígeno Carcinoembrionario (CEA). El tratamiento efectuado fue quirúrgico completándose el mismo con quimio e inmunoterapia, falleciendo la paciente a los doce meses del diagnóstico. El dosaje de las enzimas lisosomales séricas al momento del diagnóstico mostraban un valor superior al valor máximo normal, por lo que investigaciones posteriores podrían validar el dosaje de estas enzimas como método complementario para el diagnóstico de esta patología. La identificación de lesiones precursoras del melanoma maligno y la determinación de marcadores tumorales séricos junto a la aplicación de terapias locales y sistémicas mas efectivas podrían contribuir a mejorar la sobrevida de estos pacientes.

The melanoma is a melanocytic start cancer extremely strange, of serious forecast with a poor survive at five year. The aim of the present work is communicate a clinical case of mouth cavity melanoma belonging to a 75-year-old woman, in which were studied lysosomal enzymes levels, Acid Fosfatase (FA), Hexosaminidase (Hex), B-Galactosidasa (B-Gal) and the Carcinoembrionic Antigen (CEA). The treatment carried out was surgical and being completed with quimio and immunotherapy, dying twelve months latter the patient. The seric lysosomal enzymes at the moment of diagnostic showed a value over the normal one, for what this study suggested may be used as complementary method of diagnosis to this pathology. The precursor injuries identification of malignant melanoma and seric determination of tumour scoreboards with the application of local and systemic therapies more effective might help to provide better survive to these patients.

Melanoma infantil / Childhood melanoma

El melanoma en niños es poco frecuente, pero está aumentado aceleradamente, y es de mal pronóstico de no ser reconocido a tiempo. Es una entidad de difícil diagnóstico clínico y patológico, que debe considerarse en el diagnóstico diferencial de toda lesión pigmentada de la infancia. El tratamiento debe ser agresivo, y la resección quirúrgica del melanoma localizado es el único tratamiento potencialmente curativo. El manejo de la enfermedad diseminada es complejo y la quimioterapia e inmunoterapia son las principales armas terapéuticas en la actualidad.