Tasa de recurrencia e implicación del margen quirúrgico en la supervivencia del paciente con melanoma acral. ¿Es necesario un margen amplio? / Recurrence rate and survival implications of surgical margins in patients with acral melanoma. Is a wide margin necessary?

Resumen Introducción: La extensión apropiada de los márgenes de resección en el melanoma acral no está claramente establecida. Objetivo: Investigar si la escisión con margen estrecho es adecuada en el melanoma acral grueso. Métodos: Se estudiaron 306 pacientes con melanoma acral. Conforme a la extensión del margen quirúrgico (de 1 a 2 cm y > 2 cm), se analizaron los factores asociados a la recurrencia y la supervivencia. Resultados: De 306 pacientes, 183 fueron mujeres (59.8 %). La mediana del grosor de Breslow fue 6 mm; 224 casos (73.2 %) fueron de tipo ulcerados, 154 pacientes (50.3 %) tenían enfermedad en estadio clínico III, 137 en II (44.8 %) y 15 en IV (4.9 %). Todos los casos presentaron margen negativo, con una mediana de 31.5 mm. Un grosor de Breslow de 7 mm (p = 0.001) y la etapa clínica III (p = 0.031) se asociaron a recurrencia; los factores asociados a la supervivencia fueron el índice de Breslow (p = 0.047), la ulceración (p = 0.003), la etapa clínica avanzada (p < 0.001) y el uso de adyuvancia (p = 0.003). Conclusión: Un margen de resección de 1 a 2 cm no afectó la recurrencia tumoral ni la supervivencia en los pacientes con melanoma acral.

Abstract Introduction: Appropriate size of resection margins in acral melanoma is not clearly established. Objective: To investigate whether narrow-margin excision is appropriate for thick acral melanoma. Methods: Three-hundred and six patients with acral melanoma were examined. Factors associated with recurrence and survival were analyzed according to surgical margin size (1 to 2 cm and > 2 cm). Results: Out of 306 patients, 183 were women (59.8%). Median Breslow thickness was 6 mm; 224 cases (73.2%) were ulcerated, 154 patients (50.3%) had clinical stage III disease, while 137 were at stage II (44.8%) and 15 at stage IV (4.9%). All cases had negative margins, with a median of 31.5 mm. A Breslow thickness of 7 mm (p = 0.001) and clinical stage III (p = 0.031) were associated with recurrence; the factors associated with survival were Breslow index (p = 0.047), ulceration (p = 0.003), advanced clinical stage (p < 0.001), and use of adjuvant therapy (p = 0.003). Conclusion: A resection margin of 1 to 2 cm did not affect tumor recurrence or survival in patients with acral melanoma.

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.

Melanoma subungueal: un reto diagnóstico para los médicos / Subungual melanoma: a diagnostic challenge for doctors

El melanoma subungueal es un subgrupo del melanoma acral lentiginoso. Con frecuencia se diagnostica en etapa avanzada, dada la escasez de síntomas; de ahí que la evaluación y el tratamiento oportuno mejoran el pronóstico. Se presenta el caso de un paciente de 44 años de edad, que acude a consulta de Ortopedia con melanoniquia de tres meses de evolución. Había sido tratado en la atención primaria de salud por un hematoma secundario a un trauma directo sobre la falange distal del primer artejo del pie izquierdo. Fue seguido por consulta externa de Ortopedia y, al no experimentar una evolución adecuada, fue evaluado por la Comisión Provincial de Tumores Periféricos. Se le realizó una biopsia por punch (sacabocado), que arrojó el resultado de melanoma subungueal. Se realizó la amputación del primer artejo y del proximal del primer metatarsiano, una vez verificada la no existencia de lesiones metastásicas, con excelente resultado estético y funcional, sin mostrar recidiva en su seguimiento, a dos años de su intervención(AU)

Subungual melanoma is a subgroup of lentiginous acral melanoma. It is often diagnosed in an advanced stage by a shortage of symptoms, so timely evaluation and treatment improve prognosis. This is the case of a 44-year-old patient who goes to orthopedics with melanonichia 3 months of evolution. He had been treated for a bruise secondary to direct trauma to the distal phalanx of the first left foot ailre in primary health care. It was followed by external orthopedic consultation and by not following an adequate evolution was evaluated by the provincial commission of peripheral tumors. He was given a punch biopsy resulting in a subungual melanoma. The amputation of the first artejo and proximal first metatarsal was carried out, once verified the non-existence of metastatic lesions, with excellent aesthetic and functional result, without showing relapse in its follow-up to two years(AU)

Soluble PD-L1 as a prognostic factor for advanced acral and mucosal melanoma / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: Elevated levels of soluble PD-L1 (sPD-L1) are associated with worse prognosis of renal cell carcinoma and multiple myeloma. However, the regulatory roles and functions of sPD-L1 in advanced melanoma are not fully understood. This study was designed to evaluate the association between circulating sPD-L1 concentrations and prognosis of patients with advanced acral or mucosal melanoma. Methods: A total of 102 untreated patients with advanced acral and mucosal melanoma admitted to Peking University Cancer Hospital between January 2012 and December 2015 were enrolled in this study. In the meanwhile, peripheral blood samples were obtained from 40 healthy donors. Circulating sPD-L1 concentrations were determined using an enzyme-linked immunosorbent assay. Results: The advanced melanoma cohort included 58 acral melanoma patients and 44 mucosal melanoma patients. The pre-treatment concentration of sPD-L1 (2.91±2.23 ng/ml) in plasma of patients group was elevated as compared with that in healthy donors (0.59 ng/ml). The concentration of sPD-L1 in serum was significantly upregulated in 39/102 (38.2%) patients and significantly associated with increased LDH level (P=0.021) and number of Tregs (P=0.017). The overall survival rates of patients with high or low concentrations of sPD-L1 were statistically different (8.5 months [high level] vs 11.6 months [low level], P=0.022). Conclusion: sPD-L1 concentration is elevated in patients with advanced acral or mucosal melanoma, which may play an important role in predicting prognosis.

Sensitivity and Usefulness of VE1 Immunohistochemical Staining in Acral Melanomas with BRAF Mutation

BACKGROUND: Acral melanomas are known to have a low frequency of BRAF mutation, in contrary to higher KIT mutation. Recently, VE1 immunostaining was reported to have a good correlation with BRAF mutation status. OBJECTIVE: We aimed to evaluate the clinicopathological features of BRAF-mutated acral melanomas and validate the correlation of the VE1 immunohistochemical stains in those cases. METHODS: The clinical features (age, sex, anatomical site), and histopathological characteristics of 41 patients with acral melanoma were evaluated. We performed a next-generation sequencing to detect BRAF mutation status. We also determined the correlation of VE1 immunohistochemical staining with BRAF mutation status. RESULTS: Among 19 acral melanomas with BRAF mutation, common histopathological subtype was acral lentiginous melanoma (8/19, 42%) and nodular melanoma (8/19, 42%) and superficial spreading melanoma (3/19, 16%) followed. VE1 immunostaining results were positive in all 15 cases with BRAF V600E mutation (sensitivity 100%), and negative in 4 cases of BRAF non-V600E mutation. However, VE1 immunostaining was negative in all 22 patients with BRAF wild-type. CONCLUSION: VE1 immunostaining had a good correlation with BRAF V600E mutation status.

Analysis of Prognostic Factors and Development of Prognostic Model for Resectable Acral Melanoma Patients / 中山大学学报(医学科学版)

[Objective]To analyze the prognostic factors of resectable acral melanoma patients ,then develop a novel prognostic model and examined its prognostic value.[Methods]The study retrospectively analyzed clinicopathological characteristics and inflam?matory markers of 232 acral melanoma patients who underwent radical surgical resection between 2000 and 2011 at the Sun Yat-sen University Cancer Center. Kaplan-Meier curves were plotted to estimate overall survival. Significantly predictive factors were identified by multivariate Cox regression analyses and a prognostic model based on these variables was constructed to predict survival.[Results]Cox regression analysis revealed that age,lactic dehydrogenase(LDH),stage,globulin(GLB)and C-reactive protein (CRP)were independently related to survival. After computing these scores ,patients were classified into three risk groups. The new prognostic model identified three categories of patients with different prognoses(P<0.001)and significantly stratify patient prognosis in different tumor stages. The 5-year survival rate was 42.9%,25.7%,and 3.7%in groups 1,2,and 3,respectively. The AUC of new prognostic model is 0.664(95%CI:0.599-0.724).[Conclusion]Age,LDH,stage,GLB and CRP were independently related to survival in our study population,and the prognostic model is useful to stratify patients into different risk groups and it is a useful complement to AJCC staging for Asian patients with acral melanoma.

Melanoma acral lentiginoso (MAL): experiencia del Instituto Nacional de Cancerología de Colombia. 2003-2006 / Acral lentiginous melanoma (ALM): the experience of the National Cancer Institute of Colombia. 2003-2006

El Melanoma Acral Lentiginoso (MAL) es una variante de melanoma maligno, frecuente en nuestro medio, de predomino en las manos, pies y aparato ungular. En Colombia representa cerca del 15% de los casos de melanomas. Objetivo: el objetivo de este estudio es describir las características epidemiológicas, clínicas e histopatológicas de los pacientes con melanoma acral lentiginoso, atendidos en el Instituto Nacional de Cancerología de Colombia (INC), durante el período 2003-2006. Este es el primer reporte descriptivo de esta condición en nuestro país y de los pocos a nivel mundial. Métodos: estudio observacional retrospectivo tipo serie de casos, que resume las características clínicas y epidemiológicas de todos los pacientes con MAL diagnosticados en el INC, entre 2003 y 2006. Resultados: los pacientes con MAL constituyen en el INC el 25% de los casos de melanoma. Un total de 93 pacientes fueron atendidos en el INC durante el período de estudio, de los que 78 recibieron manejo quirúrgico. El porcentaje de casos avanzados (Estadios III y IV) 33% (n=31). Entre los antecedentes se registraron el de trauma previo, en el sitio de la lesión en 11 (11.8%). La mayoría (n=60-64.5%) de los pacientes, no tuvieron antecedentes de exposición solar como factor de riesgo. Tres pacientes (3.4%) registraron historia familiar de melanoma, de primer grado. El compromiso de miembros inferiores fue mayoritario (88.1%) n=82, siendo la región plantar y digital los sitios más frecuentes de presentación n=77 (94%). De los pacientes llevados a cirugía, en 59 (75%) pacientes se realizó ganglio centinela. Otras opciones terapéuticas empleadas fueron: el tratamiento adyuvante con interferón alfa realizado en 14 pacientes (18%), quimioterapia en 8 pacientes (10.2%), radioterapia en 18 pacientes (23%), cirugía más quimioterapia en 8 pacientes (10.2 %), cirugía más radioterapia en 18 pacientes (23%) y cirugía, quimioterapia más radioterapia en 3 pacientes (3.8%). Conclusión: el presente estudio describe las características epidemiológicas del MAL en Colombia y constituye el punto de partida, para el estudio local de esta variante del melanoma, frecuente en nuestra población.

Introduction: Acral Lentiginous Melanoma (ALM) is a variation of malignant melanoma which frequently occurs in Latin America; in developed countries it accounts for 2-8% of all melanoma types; in Colombia, 15% of all melanoma cases are classified as ALM. Histopathological characteristics of acral lentiginous melanoma patients treated at the National Cancer Institute of Colombia (NCI) during the years 2003-2006. This is the first descriptive report carried out on ALM in our country, and is among the few conducted in the world. Methods: an observational, retrospective study compiled the clinical and epidemiological characteristics of all acral lentiginous melanoma patients treated at the National Cancer Institute of Colombia during the years 2003-2006. Results: ALM patients accounted for 25% of all melanoma cases treated at the National Cancer Institute. A total of 93 patients were treated over the course of the study, 78 of whom underwent surgery. Advanced cases (Stages III and IV) made up 33% (n=31) of the total; among tumor antecedents, trauma at lesion site came to 11.8% (n=11). Non-solar exposure as a risk factor was reported in 64.5% (n=60) of patients; three patients (3.4%) had immediate family history of melanoma. Lower limb involvement prevailed, 88.1% (n=82) of which toes and soles of the feet were the most frequent sites, 94% (n=77). Three quarters (75%) of the 59 patients who underwent surgery received sentinel lymph node surgery. Other treatments included: adjuvant therapy with interpheron-alpha in 14 (18%) patients, chemotherapy in 8 patients (10.2%), radiotherapy in 18 patients (23%), surgery plus chemotherapy in 8 patients (10.2%), surgery plus radiotherapy in 18 patients (23%), and surgery plus chemotherapy plus radiotherapy in 3 patients (3.8%). Conclusion: this study describes the epidemiological characteristics of ALM in Colombia and provides a reference for the local study of this frequent melanoma variation in our population.

Melanoma Maligno acral en Chile: análisis clínico e histopatológicode 70 casos en la población consultante de hospitales públicos en Santiago, Chile / Acral malignant melanoma in Chile: clinical and histopathological analysis of 70 cases in Santiago, Chile

En este trabajo se analizan las características clínico patológicas del MM Acral en población consultante de hospitales públicos, en los períodos 1992-2001 y 2005-2009. La muestra contó con 70 casos, de los cuales 51.4 por ciento correspondió a sexo femenino, la edad promedio de la muestra fue 66,6 años. Casi la totalidad de los MM acrales fueron de planta de pies (97.1 por ciento). Los diagnósticos de derivación, fueron MM en el 78.6 por ciento, seguido por otros diagnósticos (17.1 por ciento). El tipo clínico más frecuente fue melanoma nodular (31.4 por ciento). El tipo histológico más frecuente fue el melanoma invasivo (62.9 por ciento). El índice de Breslow más frecuente fue > 1.7 mm en el 52.9 por ciento. Este estudio es uno de los primeros sobre MM acral en población chilena, con resultados similares a lo publicado en la literatura internacional, sin embargo, destaca una edad promedio de diagnóstico más tardía y un porcentaje no menor de derivación con otro diagnóstico.

In this study we analyze the clinical and histopathological profile of acral MM in the population attending at state hospitals, during the periods (1992-2001) and (2005-2009). We analyzed 70 cases of acral MM, 51.4 percent were females, with average age of 66.6 years old. The majority of acral MM were located in soles (97.1 percent). The main clinical diagnosis was malignant melanoma (78.6 percent); however, a 17.1 percent of acral MM showed a different clinical diagnosis. The main clinical type of MM was Nodular Melanoma (31.4 percent). The most frequent histopathological type was invasive melanoma (62.9 percent). The most frequent Breslow thickness was > 1.7 mm (52,9 percent). This study is one of the first analyses of acral MM in the Chilean population, with similar results to the observed in the international literature; however, our patients presented an older average age of diagnosis and showed an important percentage of clinical diagnosis different to Malignant Melanoma.

The Clinical Significance of Tumor-Infiltrating Lymphocytes and Microscopic Satellites in Acral Melanoma in a Korean Population

BACKGROUND: There are various histological prognostic parameters of cutaneous malignant melanoma, including tumor thickness and ulceration. Tumor-infiltrating lymphocytes (TIL) are among these parameters and can be further classified into three categories: 'absent', 'non-brisk' and 'brisk'. Brisk TIL usually indicates better clinical prognosis. Microscopic satellite (Ms) is defined as a nest of tumor cells that is greater than 0.05 mm in diameter and definitely separated from the main tumor. Even though the incidence of Ms varies according to Breslow thickness, the presence of Ms generally indicates poor prognosis. OBJECTIVE: Clinical significance of both TIL and Ms has been extensively studied in western populations but much less so in Asian countries, including Korea, where acral melanoma is the most common subtype. METHODS: We reviewed 90 patients with acral melanoma diagnosed at Kyungpook National University Hospital in Korea. Tissue specimens were examined using hematoxylin-eosin and HMB45 immunohistochemical staining. They were also evaluated by the presence and categorization of TIL (absent, non-brisk and brisk) and the presence of Ms. We further evaluated their impact on survival events (recurrence, distant metastasis and death). RESULTS: The number of survival events by TIL type was 22 in the absent category (22/64, 34.4%), 3 in the non-brisk category (3/25, 12.0%) and 0 in the brisk category. For Ms, survival events were present in 7 patients in Ms-present group (7/11, 63.6%) and 21 patients in Ms-absent group (21/79, 26.6%). CONCLUSION: We suggest the possibility of TIL and Ms as prognostic indicators for acral melanoma in Korean population.

Cyclin D1 expression in acral melanoma: a case control study in Sarawak

Acral melanoma has been reported to have distinctive clinical presentation and ethnic distribution compared to other histological types of malignant melanoma. Acral melanoma also exhibits distinctive focused gene amplifi cations, including cyclin D1 overexpression. We reviewed archived histological material of malignant melanoma in the Sarawak General Hospital from year 2004 to 2010. 43 tumours, comprising 28 acral melanoma and 15 non-acral melanoma, had suffi cient material to be included in the study. The majority (36%) of acral melanoma tumours occurred in the heel. The tumours were analyzed for cyclin D1 expression by immunohistochemistry. 68% of acral melanoma were cyclin D1 positive compared to a positivity of 33% in non-acral tumours. This difference was statistically signifi cant (p <0.05). This fi nding may improve the histological diagnosis of acral melanoma and detection of positive resection margins.

Clinical and Histopathologic Study of Acral Melanoma / 대한피부과학회지

A total of 68 primary melanorna cases diagnosed at Seoul National University Hospital for the past 10 years from 1978 to 1987 were included for this clinico pathological study. Among the 31 primary cutaneous melanomss, 19 cases (61.3%) occurred on hands or feet, especially on the plantar surfaces. The average age of patients with acral melanomas was 49.3 years at the tirne of diagnosis and the male to female ratio of 19 cases was 3.8 to 1. The clinical and histopathologic findings showed that most ecral melanomas, if not all, were the acral lentiginous type. A high incidence of metastasis (73.7%) was recognized in acral melanomas.