RESUMO
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.
Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Humanos , Idoso , Melanoma/patologia , Estudos de Coortes , Neoplasias Cutâneas/patologia , Doenças da Unha/diagnóstico , PrognósticoRESUMO
Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.
Assuntos
Melanoma , Doenças da Unha , Neoplasias Cutâneas , Humanos , Idoso , Melanoma/patologia , Estudos de Coortes , Neoplasias Cutâneas/patologia , Doenças da Unha/diagnóstico , PrognósticoRESUMO
BACKGROUND: Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a Wnt5a receptor aberrantly expressed in cancer that was shown to either suppress or promote carcinogenesis in different tumor types. Our goal was to study the role of ROR2 in melanoma. METHODS: Gain and loss-of-function strategies were applied to study the biological function of ROR2 in melanoma. Proliferation assays, flow cytometry, and western blotting were used to evaluate cell proliferation and changes in expression levels of cell-cycle and proliferation markers. The role of ROR2 in tumor growth was assessed in xenotransplantation experiments followed by immunohistochemistry analysis of the tumors. The role of ROR2 in melanoma patients was assessed by analysis of clinical data from the Leeds Melanoma Cohort. RESULTS: Unlike previous findings describing ROR2 as an oncogene in melanoma, we describe that ROR2 prevents tumor growth by inhibiting cell-cycle progression and the proliferation of melanoma cells. The effect of ROR2 is mediated by inhibition of Akt phosphorylation and activity which, in turn, regulates the expression, phosphorylation, and localization of major cell-cycle regulators including cyclins (A, B, D, and E), CDK1, CDK4, RB, p21, and p27. Xenotransplantation experiments demonstrated that ROR2 also reduces proliferation in vivo, resulting in inhibition of tumor growth. In agreement with these findings, a higher ROR2 level favors thin and non-ulcerated primary melanomas with reduced mitotic rate and better prognosis. CONCLUSION: We conclude that the expression of ROR2 slows down the growth of primary tumors and contributes to prolonging melanoma survival. Our results demonstrate that ROR2 has a far more complex role than originally described.
Assuntos
Ciclo Celular , Proliferação de Células , Melanoma/genética , Proteínas Proto-Oncogênicas c-akt/genética , Receptores Órfãos Semelhantes a Receptor Tirosina Quinase/genética , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
BACKGROUND: Melanoma epidemiological and prognostic studies are based on Caucasian populations, in whom the predominant subtype is superficially-spreading melanoma and in whom thin melanomas (Breslow < 3 mm) predominate. Mexican patients show a predominance of thick melanomas (Breslow ≥ 3 mm), and the acral subtype is the most common. There are no publications on prognostic factors in thick melanomas. We hypothesize that we will identify factors that determine the prognosis in this group of patients. OBJECTIVE: To identify clinical-pathological factors associated with the prognosis of patients with thick melanomas in the Mexican population. MATERIAL AND METHODS: Data on melanomas with Breslow > 3 mm were collected from 2010 to 2015. The prognostic influence of various clinical-pathological factors was analyzed. RESULTS: The most common subtypes were acral melanoma in 271 patients (74.9 %) and nodular melanoma in 49 (13.5 %). Median Breslow thickness was 7 mm. 56.6 % of the patients had lymph node metastases (clinical stage [CS] III), 269 (74.3 %) had ulceration, and surgical margins were positive in 15 (4.1 %). Elevated neutrophil: lymphocyte ratio (≥ 2) was found in 188 (51.9 %). The variables associated with lower overall survival were CS (p < 0.001), Breslow thickness (p = 0.044), ulceration (p = 0.004), mitotic activity (p < 0.001), < 2-cm margin (p < 0.001) and an increased neutrophil: lymphocyte ratio (p = 0.037). In the multivariate analysis, the factors associated with overall survival were CS, mitotic activity, and surgical margin. CONCLUSIONS: In patients with thick melanomas, overall survival is influenced by mitotic activity, a positive margin, and clinical stage.
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.
Assuntos
Melanoma/mortalidade , Melanoma/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Carga Tumoral , Adulto , Idoso , Feminino , Humanos , Metástase Linfática , Masculino , Margens de Excisão , Melanoma/classificação , México , Pessoa de Meia-Idade , Mitose , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Cutâneas/classificação , Úlcera/patologia , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Carga Tumoral , Melanoma/mortalidade , Melanoma/patologia , Prognóstico , Úlcera/patologia , Margens de Excisão , Metástase Linfática , Melanoma/classificação , México , MitoseRESUMO
BACKGROUND: There are no well-defined clinical factors to predict the risk of occult invasion in melanoma of the lentigo maligna type (LM) before complete histopathologic analysis. OBJECTIVE: To evaluate whether clinical size was a predictor of invasion in LM and subclinical extension. METHODS: Consecutive cases of LM were recorded in a prospectively maintained database from 2006 to 2019. Patient and tumor data were recorded during initial evaluation. The LM clinical area was calculated in square millimeters (length × width). All patients were treated with staged excision. RESULTS: We included 600 patients. The mean age was 65.9 years (standard deviation, 12.3; range, 27-95 years); 62.8% (n = 377) were men. The mean LM clinical area was 128.32 mm2 for in situ lesions versus 200.14 mm for invasive lesions (P = .1). Based on quantile regression, the median margin required for complete removal increased with LM clinical area. LIMITATIONS: The study was performed in a tertiary cancer center with possible referral bias and more complex cases. CONCLUSIONS: LM can present with variable clinical size, which may correlate with subclinical extension; however, the presence of invasion is not well estimated by LM clinical area.
Assuntos
Sarda Melanótica de Hutchinson/diagnóstico , Cirurgia de Mohs , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Sarda Melanótica de Hutchinson/patologia , Sarda Melanótica de Hutchinson/cirurgia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica/diagnóstico , Prognóstico , Estudos Prospectivos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Carga TumoralRESUMO
AIM: To analyze the accuracy of the sentinel lymphatic node biopsy (SLNB) and to investigate predictive factors for sentinel node (SN) status and prognostic factors for recurrence-free survival (RFS) and disease-specific survival (DSS) in patients with melanoma. MATERIAL AND METHODS: Between June 1997 and June 2017, 440 consecutive patients, who underwent SLNB by a single surgical team, were prospectively included. Descriptive and survival analysis were performed. RESULTS: 119 of 440 patients (26%) had positive SN. SLNB's false-negative rate was 6.3%. Breslow thickness, Clark´s level, ulceration and histological subtype were statistically significant predictive factors of SN metastases. In a multivariate analysis, positive SN (HR = 2.21, p = 0.01), deeper Breslow thickness (HR = 2.05, p = 0.013), male gender (RR = 2.05, p = 0.02), and higher Clark's level (HR = 2.30, p = 0.043) were significantly associated with decreased RFS; and positive SN (HR = 2.58, p < 0.001), deeper Breslow thickness (HR = 2.57, p = 0.006) and male gender (HR = 1.93, p = 0.006) were associated with lower DSS. CONCLUSION: SLNB is a reliable and reproducible procedure with high sensitivity (93.7%). Positive SN metastases, Breslow thickness and male gender were statistically associated with poorer outcomes. Male gender was an independent prognostic factor of tumor thickness or SN status.
Assuntos
Melanoma/patologia , Recidiva Local de Neoplasia/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Prospectivos , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/secundário , Neoplasias Cutâneas/cirurgia , Análise de Sobrevida , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Antecedentes: En la octava edición del manual de estadificación del cáncer del American Joint Committee on Cancer (AJCC), se introdujeron cambios importantes en las categorías T, N y M. Al entrar en vigencia la octava guía de la AJCC, se modificó no solo el T, sino también la indicación de biopsia del ganglio centinela (BGC). Entre los cambios más significativos en la estadificación se encuentran: la exclusión del índice mitótico (IM) de la categoría T en los melanomas finos (de hasta 1 mm de espesor) y el cambio del punto de corte para el espesor tumoral para discriminar un T1a (< 0,8 mm sin ulceración) de un T1b (≥ 0,8 mm). Objetivo: Comparar la estadificación inicial de los melanomas finos según el criterio utilizado en la séptima edición, con la que tendrían de acuerdo con la perspectiva actual del AJCC, con especial atención en el índice mitótico. Diseño y métodos: Estudio observacional, de corte transversal, realizado mediante la recolección de datos de las historias clínicas desde el 1 de enero de 2000 hasta el 31 de diciembre de 2017. Resultados: De 131 melanomas finos incluidos, 28 tendrían cambios en su estadificación. Al considerar el nuevo punto de corte para el espesor tumoral, 22 melanomas T1a pasarían a T1b. Asimismo, se detectaron 20 melanomas con un IM ≥ 1 mitosis/mm2, de los cuales solo 6 tuvieron indicación de BGC por este criterio exclusivamente y serían clasificados como T1a en la actualidad. De estos, en 2 no se realizó la BGC por autodeterminación de los pacientes y en los 4 restantes el resultado fue negativo. Conclusiones: Veintiocho de nuestros pacientes tendrían hoy diferencias en la indicación de BGC: 22 serían considerados con mayor riesgo de metástasis ganglionares y serían candidatos a su pesquisa. Los otros 6 pacientes ya no tendrían indicación de ese estudio por la baja posibilidad de encontrar metástasis ocultas, lo cual coincide con el resultado negativo de la BGC en los 4 pacientes que se sometieron al procedimiento. (AU)
Background: In the 8th edition of the cancer staging manual of the American Joint Committee on Cancer (AJCC), important changes were made in the T, N and M categories. When the 8th guideline of the AJCC came into effect, not only was the T stage modified, but also the indication for sentinel lymph node biopsy (SLNB). The most significant changes in staging included: the exclusion of the mitotic index (MI) as a determinant of the T category and the change of the threshold of tumor thickness to discriminate a T1a (< 0.8 mm without ulceration) from a T1b (≥ 0.8 mm). Objective: To compare the initial staging of thin melanomas according to the criteria used in the 7th edition, with the one that would have been used according to the current AJCC recommendations, with special focus on MI. Design and methods: Observational, cross-sectional study, carried out through the collection of data from medical records from January 1, 2000 to December 31, 2017. Results: There were 131 thin melanomas included, 28 of which would have had changes in their staging. When considering the modified threshold for tumor thickness, 22 T1a melanomas would be classified as T1b. Among 20 thin melanomas with a MI ≥ 1, only 6 had an indication for SLNB solely due to the MI criterion and would be now classified as T1a. Two of these did not undergo SLNB because they rejected the procedure, and in the remaining 4, there were no SLN metastasis. Conclusions: Nowadays, 28 of our patients would have differences in the indication for SLNB: 22 would be considered to be at greater risk of lymph node metastasis and would be candidates for screening. The other 6 patients would no longer have an indication for this procedure due to the low probability of clinically occult metastases, which seems to concur with the negative result of SLNB in the 4 patients who underwent the procedure. (AU)
Assuntos
Humanos , Neoplasias Cutâneas/patologia , Guias de Prática Clínica como Assunto , Biópsia de Linfonodo Sentinela , Melanoma/patologia , Índice Mitótico , Estadiamento de Neoplasias/métodos , Neoplasias Cutâneas/diagnóstico , Estudos Transversais , Fatores de Risco , Metástase Linfática , Melanoma/diagnósticoRESUMO
Nowadays, histopathological criteria for melanocytic lesions are the mainstay prognostic factors for melanoma. However, there are cases in which these parameters fall short to predict melanoma spread. We recently demonstrated a correlation of cofilin-1 levels, a key protein for tumor invasion, with different histopathological parameters associated with melanoma malignancy as well as a negative correlation with survival. In order to broaden our previous findings, we aim to estimate the probability of a melanoma to metastasize as a function of both a conventional histopathological parameter (Breslow thickness, BT) and cofilin-1's immunohistochemical expression levels, which we propose as a potential marker for metastasis. We used a Bayesian approach to analyze clinical and cofilin-1 datasets formerly obtained from a patients' small cohort diagnosed with malignant melanocytic lesions since 2000 until 2008; classified at different tumor stages with or without detected metastasis and with at least 5 years of clinical follow-up. Low BT values exhibited wide variance to predict metastasis occurrence, while the differential diagnostic value of cofilin-1 confirmed BT diagnosis or resulted more precise to predict outcome. Particularly, the probability of metastasis estimation improved when cofilin-1 was combined with BT for specific cases, where BT displayed large uncertainties. Our analysis and the cofilin-1 determination provided statistically significant prognostic value in mid-low BT melanomas, which could complement further evaluation criteria to assist diagnosis and treatment decision-making. Moreover, the combined use of cofilin-1 with BT, if validated in follow-up studies, would be feasible to help patients' selection for treatment and optimize health resources.
Assuntos
Cofilina 1/metabolismo , Melanoma/diagnóstico , Metástase Neoplásica/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Argentina , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
INTRODUCTION: The study of the Sentinel Lymph Node (SLN) in Melanoma is a procedure that aims the identification of the first node to which the affected cutaneous sector drains in order to avoid unnecessary lymphadenectomies. The present study documents the frequency of identification of SLN; the relationship between positive SLN (PSLN) and recurrence, between the Breslow index (BI) and PSLN, and between BI and disease recurrence. METHOD: We analyzed the records of 148 patients with melanoma stages I and II undergoing lymphatic mapping and GC biopsy from 1999 to 2017 in a third level institution in Córdoba, Argentina. We performed preoperative lympho centellography, lymphatic mapping with combined technique and SLN biopsy. Postoperative controls were established in order to detect recurrences. RESULTS: SLN was identified in 145 patients (97.9%), being positive in 25 cases (17.2%). Recurrence was detected in 10 (8.3%) patients with negative SLN (NSLN), and in 2 (9.09%) with PSLN (p = 0.188). The median BI was 2 mm in PCG patients and 1.2 mm in GCN patients (p = 0.002). The mean BI in patients with recurrence was 2.77 mm, and 2.01 mm in those who did not show relapse (p = 0.311). CONCLUSIONS: The combined technique allows a high GC identification rate. A greater tendency to recurrence was observed in the presence of CPG. A statistically significant relationship between GCP and IB was found. The GC technique is effective and replicable in our environment.
INTRODUCCIÓN: El estudio del ganglio centinela (GC) en el melanoma maligno es un procedimiento que busca la identificación del primer ganglio al cual drena el sector cutáneo comprometido a fin de evitar linfadenectomías innecesarias. El presente estudio documenta la frecuencia de identificación del GC y la relación entre GC positivo (GCP) y recurrencia, entre el índice de Breslow (IB) y GCP, y entre el IB y la recurrencia de la enfermedad. MÉTODO: Se analizaron los registros de 148 pacientes con melanoma maligno en estadios I y II sometidos a mapeo linfático y biopsia de GC desde 1999 hasta 2017 en una institución de tercer nivel de Córdoba, Argentina. Se realizaron linfocentellografía preoperatoria, mapeo linfático con técnica combinada y biopsia de GC. Se establecieron controles posoperatorios reglados a fin de detectar recurrencias. RESULTADOS: Se identificó el GC en 145 pacientes (97.9%) y resultó positivo en 22 (17.2%). Se detectó recurrencia en 10 pacientes (8.3%) con GC negativo (GCN), y en 2 (9.09%) con GCP (p = 0.188). La mediana del IB fue de 2 mm en los pacientes con GCP y de 1.2 mm en los pacientes con GCN (p = 0.002). La media del IB en los pacientes con recurrencia fue de 2.77 mm, y en los que no mostraron recaída fue de 2.01 mm (p = 0.311). CONCLUSIONES: La técnica combinada permite una alta tasa de identificación del GC. Se observó una mayor tendencia a la recurrencia en presencia de GCP. Se comprobó una relación estadísticamente significativa entre GCP e IB. La técnica del GC es efectiva y replicable en nuestro medio.
Assuntos
Melanoma/secundário , Recidiva Local de Neoplasia , Biópsia de Linfonodo Sentinela/métodos , Linfonodo Sentinela/patologia , Neoplasias Cutâneas/secundário , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
El melanoma maligno ha aumentado su incidencia. En la provincia de Osorno, para el período 2016 2018, se registraron 55 casos nuevos de melanoma, con predominio en sexo femenino. Los subtipos extensivo superficial y nodular fueron los más frecuentes; no obstante el lentiginoso acral fue un grupo prevalente, siendo el sexo masculino el más afectado por esta variedad. Un 49,1% de los melanomas fueron detectados con Breslow mayor a 1 mm, siendo los hombres los más afectados por una pesquisa más tardía. Reforzar la cobertura de la atención primaria urbana y rural, como así la oferta de dermatólogos, impactarán en la mejora de estos índices.
The Malignant Melanoma has increased its incidence. In the province of Osorno, between 2016 2018 there were 55 new cases of melanoma, with predo-minance in the female sex. The superficial spreading and nodular subtypes were most common. However the acral lentiginous was a prevalent group, with the male sex being the most affected by this variety. A 49,1% of melanomas were detected with Breslow greater than 1mm, with men being the ones who presented later inquiries. The coverage of urban and rural primary care needs to be strengthened, just like supply of dermatologists, it will impact the improvement of these rates.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/epidemiologia , Melanoma/epidemiologia , Neoplasias Cutâneas/patologia , Chile/epidemiologia , Estudos Retrospectivos , Distribuição por Idade e SexoRESUMO
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.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Cutâneas/patologia , Biópsia de Linfonodo Sentinela , Linfonodo Sentinela/patologia , Melanoma/patologia , Linfonodo Sentinela/cirurgia , Excisão de Linfonodo , Metástase LinfáticaRESUMO
This study highlights the systemic oxidative changes in patients submitted to primary cutaneous melanoma removal. Cutaneous melanoma is highly aggressive and its incidence is increasing worldwide. We evaluated systemic oxidative stress (OS) and 3-nitrotyrosine (3-NT) expression in melanoma tissue in relation to the Breslow thickness in patients under surveillance. Forty-three patients with cutaneous melanoma and 50 healthy volunteers were recruited. Patients were divided into two groups according to the tumor's Breslow thickness: T1/T2 (<2 mm) and T3/T4 (≥2 mm). Systemic OS and inflammatory mediators were evaluated in plasma, and the 3-NT expression was analyzed via immunohistochemistry. Compared with the controls, the patients had lower blood levels of reduced glutathione, higher malondialdehyde and thiol levels, and a higher total radical-trapping antioxidant parameter to uric acid ratio. The C-reactive protein and γ-glutamyl transpeptidase were increased only in the T3/T4 group. High levels of 3-NT were present only in T3/T4 patients. Our data suggested that a correlation exists between the Breslow thickness and a systemic pro-oxidant status, and that oxidative changes induced by the melanoma remain in the microenvironment post-surgery, demonstrating a role for oxygen species in melanoma.
Assuntos
Melanoma/metabolismo , Melanoma/cirurgia , Estresse Oxidativo/fisiologia , Microambiente Tumoral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas , Tirosina/análogos & derivados , Tirosina/metabolismo , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
OBJECTIVES: The clinical significance of nevus-associated melanoma compared with de novo melanomas remains controversial. It has been suggested that nevus-associated melanomas have a higher Breslow thickness and therefore worse prognosis. Over a 10-year period, this study evaluated the incidence of nevus-associated melanoma and its prognostic significance related to clinicopathologic features. METHODS: Cross-sectional study from 1995 through 2004 in a dermatopathology referral center. With available data, we evaluated sex, primary location, histologic subtype, Breslow thickness, Clark level, presence of ulceration, associated lesion, and histologic subtype of the associated lesion. RESULTS: Of 135,653 pathologic records from skin biopsy specimens over a 10-year period, 1,190 melanoma records were selected. Nevus-associated melanomas corresponded to 390 (32.8%) melanomas, with thin melanomas having a nevus 1.52 times the association observed with thick melanomas (>1.01 mm; 95% confidence interval, 1.16-1.99; P < .001). Superficial spreading melanoma was the most frequent, while no lentigo maligna melanoma was associated with nevi. The median Breslow thickness of nevus-associated melanomas was lower than that of de novo melanomas. CONCLUSIONS: Nevus-associated melanomas, which represent one-third of the melanomas in southeast Brazil, are associated with intermittent sun exposure, superficial spreading melanomas, and lower Breslow thickness. This is one of the largest series describing nevus-associated melanomas in Latin America.
Assuntos
Melanoma/patologia , Nevo/patologia , Neoplasias Cutâneas/patologia , Brasil/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Melanoma/epidemiologia , Nevo/epidemiologia , Nevo Pigmentado/epidemiologia , Nevo Pigmentado/patologia , Prognóstico , Neoplasias Cutâneas/epidemiologia , Luz Solar/efeitos adversos , Melanoma Maligno CutâneoRESUMO
A pesar de las campañas preventivas no se ha logrado disminuir la incidencia de las neoplasias cutáneas, probablemente por las alteraciones de la capa de ozono, con el consecuente aumento de la radiación ultravioleta, por eso en países del trópico se presentan lesiones como el melanoma de piel, que es considerado como una de las lesiones tumorales más agresivas. La cara y el cuello son zonas del cuerpo con una alta exposición solar, reflejándose en un mayor número de casos de este sombrío tumor. El mayor factor pronóstico en contra de los pacientes que padecen esta enfermedad es la presencia de metástasis ganglionares, por eso el grupo tratante debe esclarecer si están presentes, debido a esto hace varias décadas se realizan disecciones de cuello profilácticas, pero en la mayoría de los casos los ganglios extirpados son negativos. Una posible solución para evitar esto, es la extracción del o de los primeros ganglios que drenan el sitio del tumor primario (Ganglio Centinela). En el área de cabeza y cuello usualmente están presentes varios a la vez, lo que dificulta tomar la decisión de cuál extirpar. En nuestro grupo hemos iniciado la estandarización de esta técnica, y como abordaje inicial se realizó el primer caso de una paciente con melanoma de la cara a quien se practicó resección local amplia del tumor y extracción de los centinelas marcados por linfogammagrafía y a la vez disección de los relevos ganglionares positivos para drenaje demostrados por este estudio de medicina nuclear.
In spite of preventative campaigns having been mounted, it still has not been possible to reduce cutaneous neoplasia incidence, probably due to alterations in the ozone layer. This has led to a consequent increase in ultraviolet radiation and thus lesions occurring in tropical countries such as skin cancer (melanoma), considered as being one of the most aggressive tumour lesions. The face and neck are the body areas having the highest exposure to the sun, being reflected in a greater number of such tumour cases. The presence of ganglion metastasis is the greatest negative prognostic factor for patients suffering from this disease; the treating group must thus clarify whether this is present as prophylactic neck dissections were made several decades ago, but the ganglions so removed were negative in most cases. Extracting the first ganglions draining the primary tumour site (sentinel ganglion) represents a possible solution for avoiding this. Several of them are usually present at the same time in the head and neck area, thereby hampering taking a decision as to which should be removed. Our group has begun to standardise such technique; an initial approach has involved the first case of a patient with melanoma of the face who underwent wide local resection of the tumour and extraction of the sentinel ganglions. These were dyed and lymphogammagraphy was used, at the same time as dissection of positive ganglion relief for drainage, as demonstrated by this nuclear medicine study.
RESUMO
El melanoma lentiginoso acral (MLA) es una variante rápidamente progresiva del melanoma maligno (MM). Constituye el 5-10% de los MM y se presenta con mayor frecuencia en pacientes de raza negra, asiáticos y latinoamericanos. En Colombia, la frecuencia de MM se encuentra en aumento y el MLA es una de las variantes más comunes (14,7% de todos los melanomas). La edad promedio de presentación es de 58 años, con una tasa de supervivencia menor para las personas de raza negra, asociada al diagnóstico tardío. EL MLA se localiza en las plantas, palmas y regiones subungueales y en su etiopatología se ha descrito la presencia de mutaciones en varios genes: 9p21 p16: (67%), 11q13 (CCND1) (47%), 22q11-q13 (40%) y 5p15 (20%). El diagnóstico de MLA se ha fundamentado clásicamente en la histopatología; sin embargo, otros métodos como la dermatoscopia, la evaluación del ganglio centinela y la detección de alteraciones en las proteínas del ciclo celular pueden contribuir al diagnóstico precoz y a mejorar el pronóstico tanto del MLA como del MM en general.
Acral lentiginous melanoma (ALM) is a rapidly progressive variant of malignant melanoma (MM). It constitutes 5-10% of all cases of MM and its prevalence is higher in blacks, Asians and Latin Americans. In Colombia, the incidence of MM is increasing and ALM is one of its most common variants (14.7% of all melanoma cases). The mean age at presentation of the disease is 58 years, and the survival rate is lower in black people, partly due to delayed diagnoses. ALM is located in the soles, palms and subungual regions. Mutations in several genes have been described in the pathogenesis of ALM, namely: 9p21 (p16: 67%), 11q13 (CCND1) (47%), 22q11-q13 (40%) and 5p15 (20%). The diagnosis of ALM has been traditionally based on histopathology; however, other diagnostic tools such as dermoscopy, evaluation of the sentinel lymph node and detection of alterations in proteins that control the cell cycle, may contribute to earlier diagnoses and, consequently, improve the prognosis of both ALM and MM.
Assuntos
Biópsia de Linfonodo Sentinela , MelanomaRESUMO
El Melanoma Maligno Cutáneo es el más letal de los tumores de la piel. Afecta especialmente a individuos de raza blanca con antecedentes de exposición intensa a la luz solar, mientras que en pieles más oscuras tiene mayor incidencia en áreas poco expuestas. Objetivo: Conocer las características epidemiológicas, clínicas e histopatológicas de la población con Melanoma Maligno Cutáneo y determinar el tiempo de sobrevida posterior al diagnóstico. Material y métodos: Se analizaron retrospectivamente las historias clínicas y láminas histopatológicas de 40 pacientes en el Hospital Militar Central con diagnóstico de Melanoma Maligno Cutáneo durante los años 1985-2007. Para la evaluación de la sobrevida, se ubicó al paciente/familiares. El análisis estadístico se realizó mediante el método de Kaplan-Meier. Resultados: La edad media fue de 60,7 años, siendo el grupo etáreo mayormente afectado el de 70-79 años en ambos sexos. Hombres fueron el 70% y mujeres el 30%. No se identificó Melanoma Maligno Cutáneo familiar. El tiempo de enfermedad promedio previo al diagnóstico fue de 25,1 meses. La localización mayormente afectada fue la extremidad inferior (55%), específicamente el pie (86,4%). El 17,5% fueron de raza blanca. Los tipos clínico-histológicos más frecuentes fueron el acral (52,8%) y el nodular (22,2%). La mayor frecuencia de Melanoma Maligno Cutáneo correspondió al Nivel Clark IV y Breslow mayor que 2mm. La sobrevida acumulada a 1 año fue 81,8%; a 5 años 41,8% y a 10 años 25,9%. Conclusión: El melanoma lentiginoso acral en los pies, es el tipo clínico-histológico más frecuentemente encontrado en el Hospital Militar Central. La sobrevida fue mayor cuando el Índice de Breslow fue 1mm y el Nivel de Clark III.
The cutaneous malignant melanoma is the more letal skin tumor. It specially affects white persons with previous intense exposition to light radiation, in those with more pigmented skin affects less exposed body areas. Objective: To know clinical, epidemiologic and histopathologic features of those with cutaneous malignant melanoma and to determine the period of life after diagnosis. Material and methods: The patient records and histopathology slides of 40 patients with cutaneous malignant melanoma between 1985 and 2007 were retrospectively analyzed. For evaluation of time of life after diagnosis the patient or relatives were interviewed. Statistical analysis was made with Kaplan-Meier method. Results: The median age was 60,7 years and more affected was the age range of 70-79 years in both sexes. Seventy per-cent were men and 30% women. No cases of familial cutaneous malinant melanoma was identified. The average time of illness until diagnosis was 25,1 months. Inferior extremity wasmore affected (55%), specially the foot (86,4%). Only 17,5% were whites. The clinic histology type more frequently found was acral (52,8%) and nodular (22,2%). More frequently the cutaneous malignant melanoma belonged to Clark IV level and Breslow more than 2 mm. At one year 81,8% were alive; at 5 years the 41,8% and at 10 years the 25,9%. Conclusion: Acral lentiginous melanoma of feet was the most common type found. The overlive was high when Breslow Index was equal or less than 1 mm and Clark level was III or less.