Melanoma maligno cutáneo con metástasis sistémica en una hembra de tigre de bengala blanca (Panthera tigris tigris) / Cutaneous Malignant Melanoma with Systemic Metastasis in a Female White Bengal Tiger (Panthera tigris tigris)

Resumen La presencia del melanoma maligno cutáneo en felinos exóticos está pobremente reportada. Una hembra de tigre de Bengala blanca (Panthera tigris tigris), de 6 años, no castrada, solitaria y viviendo en un ambiente adecuado, fue evaluada por la presencia de una masa cerca del ojo izquierdo. La histopatología de la biopsia remitida mostró la presencia de melanocitos con características anaplásicas (pleomorfismo, citomegalia, cariomegalia, binucleación), área hemorrágica y foco inflamatorio fibrinoso. El diagnóstico histopatológico fue melanoma maligno. Dos meses después del diagnóstico, la tigresa manifestó un deterioro considerable con pérdida de peso y presencia de una masa redonda en el cuello. En aquel momento, por su tamaño, el melanoma obstruía totalmente la visión. Con base en esto, y por razones humanitarias, el animal fue eutanasiado. Al momento de la necropsia, se observó metástasis en pulmones, pleura y riñones. Este caso evidencia la importancia de dar a conocer la presentación de melanomas en especies poco reportadas.

Abstract The occurrence of cutaneous malignant melanoma in exotic felids is poorly reported. A 6-year-old, unneutered, solitary, female white Bengal tiger (Panthera tigris tigris), living in a suitable environment, was evaluated for the presence of a mass near the left eye. Histopathology of the referred biopsy showed the presence of melanocytes with anaplastic features (pleomorphism, cytomegaly, karyomegaly, binucleation), hemorrhagic area and fibrinous inflammatory focus. The histopathological diagnosis was malignant melanoma. Two months after diagnosis, the tigress manifested considerable deterioration with weight loss and the presence of a round mass on the neck. At that time, because of its size, the melanoma totally obstructed vision. Based on this, and for humane reasons, the animal was euthanized. At the time of necropsy, metastasis was observed in the lungs, pleura and kidneys. This case demonstrates the importance of raising awareness of melanomas in underreported species.

The effect of autophagy and crosstalk with apoptosis induced by Ultraviolet in A375 / 实用医学杂志

Objective To investigate the autophagy effect and the crosstalk with apoptosis by UV in A375 cells.Methods GFP-RFP-LC3 lentivirus were used to evaluate the effect of autophagy after being irradiated with UV of different doses (0、10、30、50 mJ/cm2).After being treated with 30 mJ/cm2 irradiation,the apoptosis rate of A375 with or without autophagy inducer was evaluated by annexin V-FITC/PI with flow cytometry.Western blot was used to distinguish the biomarker of autophagy (BECN,LC3) and apoptosis (Caspase 3,9).Results After being irradiated with 10 mJ/cm2 or 30 rnJ/cm2 UV,the autophagosome was observed at 6 h and rich at 9 h.However,the dots of autophagy had been abundant continually from 3 h with 50 mJ/cm2.The ability of inducing autophagy of UVB is stronger than UVA.UVA and UVB showed synergistic effect in autophagy with the dose of 30 mJ/cm2.The Caspase 3 and Caspase 9 proteins were downregulated after 30 mJ/cm2 UV irradiation with autophagy biomarkers increasing,whereas the apoptosis biomarkers were enriched with the inhibition of autophagy.Conclusions UV can induce autophagy with more significant effect of UVB.Autophagy paly protective role by delaying apoptosis after 30 mJ/cm2 UV irradiation in A375.

Expression of lncRNA TUSC7 in melanoma A375 cell line and its effect on proliferation and apoptosis of melanoma cells / 临床与实验病理学杂志

Purpose To investigate the expression level and the role of TUSC7 in human cutaneous malignant melanoma (CMM).Methods Quantitative real time-PCR (qRT-PCR) assay was performed to detect the expression of TUSC7 in 60 cases of CMM tissues,20 cases of benign nevus,4 CMM cell lines,and one normal human epidermal melanocytes.Then overexpression of TUSC7 was performed and its role in tumor progression was explored.Results TUSC7 expression was significantly downregulated in primary CMM tissues (n =60) compared to benign nevi (n =20),which were significantly downregulated in all the four melanoma cell lines,especially in A375 cells,compared with the normal melanocytes cells (all P ＜ 0.05).In comparison with the A375 cells transfected with the empty plasmid,those transfected with pcDNA-TUSC7 showed an obvious decrease in the proliferation and colony formation activity,while increase in the apoptosis rate (all P ＜ 0.05).Conclusion Our results suggested that the dysregulation of TUSC7 may play an important role in the CMM progression.

Formas cutáneas y mucosas infrecuentes de melanoma: parte I / Skin and mucosal forms infrequent melanoma: part I

Se han descrito varios subtipos infrecuentes de melanoma maligno en la literatura médica. A pesar de su baja frecuencia ­ que no suele superar el dos por ciento en varias series de melanoma ­ es muy importante reconocerlos precozmente pues un diagnóstico tardío está asociado a un muy mal pronóstico. En esta primera parte incluiremos; melanoma animal, melanoma desmoplásico, melanoma dérmico primario, melanoma en mucosas y melanoma nevoide.

Several infrequent subtypes of malignant melanoma have been described in the medical literature. Although their low frequency ­ less than two percent in various series of melanoma ­ it is very important to early recognize them because late diagnosis is associated with a very poor prognosis. In this first manuscript we will include; animal melanoma, desmoplastic melanoma, dermal melanoma, mucous melanoma and nevoid melanoma.

Formas cutáneas y mucosas infrecuentes de melanoma: parte II / Skin and mucosal forms infrequent melanoma: part II

Se han descrito varios subtipos infrecuentes de melanoma maligno en la literatura médica. A pesar de su baja frecuencia ­ que no suele superar el dos por ciento en varias series de melanoma ­ es muy importante reconocerlos precozmente pues un diagnóstico tardío está asociado a un muy mal pronóstico. En esta segunda parte incluiremos: melanoma verrugoso, melanoma polipoideo, melanoma hipomelanótico y amelanótico, melanoma folicular, melanoma spitzoide, melanoma con diferenciación no melanocítica.

Several infrequent subtypes of malignant melanoma have been described in the medical literature. Although their low frequency ­ less than two percent in various series of melanoma ­ it is very important to early recognize them because late diagnosis is associated with a very poor prognosis. In this second part we will include: verrucous melanoma, polypoid melanoma, hypomelanotic and amelanotic melanoma, follicular melanoma, spitzoid melanoma and non-melanocytic differentiation melanoma.

Expression and significance of autophagic gene Beclin 1 and MAP1 LC3 protein in cutaneous malignant melanoma / 临床与实验病理学杂志

Purpose To detect the expression of autophagic genes Beclin 1 and MAP1LC3 in cutaneous malignant melanoma and to ex-plore the relationship between autophagia and malignant melanoma. Methods 85 cases of speicmens including normal skin tissue, in-tradermal nevi, radial growth phase melanomas, vertical growth phase melanomas, and metastatic melanoma were collected, and the protein expression of Beclin 1 and MAP1LC3 were evaluated by immunohistochemistry of SP methods. Results The Beclin 1 and MAP1LC3 expression were pretended to be 100% in normal skin tissue, and they were declined to 85% and 95% in intradermal nevi, 58% and 50% in radial growth phase melanomas, 49. 5% and 44. 4% in vertical growth phase melanomas, both of 17% in melanoma metastases (P<0. 05). Conclusion Beclin 1 and MAP1LC3 autophagic gene expression were significantly decreased with tumor pro-gression, as well as was correlated with conventional histopathologic prognostic factors.

Algunos factores pronósticos de interés en el melanoma maligno cutáneo / Some interesting prognostic factors related to cutaneous malignant melanoma

INTRODUCCIÓN. El objetivo de esta investigación fue determinar el valor pronóstico independiente y la supervivencia entre 3 y 5 años de los factores pronósticos clínico-patológicos más importantes, y en cada etapa, según el sistema de estadificación patológica tumor-nódulo-metástasis (TNM), en pacientes con melanoma maligno cutáneo (MMC). MÉTODOS. Se realizó un estudio retrospectivo, descriptivo y longitudinal, aplicando el modelo de riesgo proporcional de Cox y el método de Kaplan Meier, dirigido a la búsqueda de diferentes variables de riesgo en pacientes con MMC. Se estudiaron 157 casos de pacientes con MMC, atendidos en un intervalo de 8 años (1993 a 2001), diagnosticados y tratados en el Instituto Nacional de Oncología y Radiobiología de La Habana. RESULTADOS. Las variables pronósticas más poderosas relacionadas con la enfermedad localizada (etapa I y II) fueron el espesor de Breslow (P: 0,000), el índice mitótico (P: 0,004), y el nivel de Clark (P: 0,04); entre las variables relacionadas con la enfermedad regional (etapa III) el número de ganglios linfáticos afectados fue la de mayor peso (P: 0,000) y la más importante en la etapa IV fue la metástasis visceral a distancia (P: 0,003). La supervivencia fue descendiendo según avanzaba la etapa patológica de la enfermedad. CONCLUSIONES. Los factores pronósticos independientes más destacados fueron el índice de Breslow, el número de nódulos linfáticos regionales afectados y las metástasis viscerales a distancia, lo cual está avalado por el consenso mundial. Sin embargo, variables como edad, sexo, sitio de la lesión, ulceración, respuesta inflamatoria hospedero-tumor, subtipo histológico, satelitosis y metástasis en tránsito, distinguidas como indicadores pronósticos independientes en grandes casuísticas, no mostraron significación estadística en este trabajo(AU)

INTRODUCTION: The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM). METHODS: A longitudinal, descriptive and retrospective study was conducted applying the Cox proportional risk form and the Kaplan-Meier method, aimed to search of different risk variables in patients with CMM. We studied 157 patients with CMM, seen during 8 years (1993 to 2001), diagnosed and treated in National Institute of Oncology and Radiobiology of La Habana. RESULTS: The more powerful prognostic variables related to localized disease (stage I and II) were the Breslow density (P: 0,000), the mitosis rate (P: 0,004), and the Clark level (P: 0,04); among the variables related to the regional disease (stage III) the number of lymphatic ganglia involved was the more weighthy (P:0,000) and the more important in Stage IV was the distant visceral metastasis (P:0,003). Survival was decreasing according to the advance of the pathological stage of disease. CONCLUSIONS: The more involved independent prognostic factors were the Breslow rate, the number of involved regional lymphatic nodules and the distant visceral metastasis, which is endorsed by a world consensus. However, variables as age, sex, lesion site, ulceration, host-tumor inflammatory response, histological subtype, satellitosis and transient metastasis, considered as independent prognostic indicators in big casuistries, had not statistical significance in present paper(AU)

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

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

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

Situación del melanoma maligno cutáneo en el Hospital Militar Central Lima, 1985û2007 / Situation of cutaneous malignant melanoma at "Hospital Militar Central-Lima", 1985-2007

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.

Up-regulation of Human Leukocyte Antigen G Expression in Primary Cutaneous Malignant Melanoma Associated with Host-vs-tumor Immune Response / 华中科技大学学报（医学）（英德文版）

Human leukocyte antigen G (HLA-G) is one of the molecules implicated in immunotolerance. To investigate the role of HLA-G in primary cutaneous malignant melanoma (CMM), a series of 47 skin melanocytic lesions were immunohistochemicaily evaluated. The correlation between HLA-G expression and CMM clinicohistopahtologicai data and Bcl-2 expression was also analyzed.HLA-G expression was detected in a variety of cell types. No significant difference in HLA-G expression was observed between malignant and non-malignant melanocytic lesions. HLA-G expres- sion was significantly correlated with the inflammatory infiltration and Bel-2 expression, whereas no significant correlation with ulceration, tumor thickness, clinical stage, histopathologicai subtypes were observed. HLA-G expression may be the result of host immune reaction in tumor microenvi- ronment rather than a malignant feature of CMM.

Clinicopathological Features of Cutaneous Malignant Melanoma / 대한피부과학회지

BACKGROUND: Malignant melanoma is the leading cause of death among skin cancers in western countries. The incidence of melanoma has been steadily increasing over the last 20 years, and age and sex distribution, anatomic location, clinicopathologic subtypes, and prognostic factors of malignant melanoma are also well known. However, various clinicopathologic aspects such as incidence, clinicopathologic subtypes and tumor behaviors are quite different in Asian and black skin. OBJECTIVE: The purpose of this study was to investigate the clinicopathologic behavior and statistics of malignant melanoma patients of Kyungpook National University Hospital, and to evaluate prognostic predictors. METHODS: Of the 97 out of 103 patients diagnosed with malignant melanoma at the Department of Dermatology of Kyungpook National University Hospital over a 14 year period (1992~2006), we analyzed mean age of onset, gender, tumor location, duration, tumor number, color, tumor thickness, Clark's level, pathologic ulceration, tumor- infiltration lymphocytes, clinicopathologic subtype, and clinical AJCC stage. Univariate analysis and multivariate analyses for survival, according to clinical and histologic tumor settings, were performed by means of the Cox proportional hazard model. Survival curves were plotted by the Kaplan-Meier method. RESULTS: Ninety-seven melanomas were identified and analyzed by both clinical behavior and pathology. Of these, 44 were male and 53 were female patients and the mean age was 59.7 years. Most of the tumors were located on the hands and feet. Thin melanoma was the most common tumor and histologic ulcerations were observed in 37 out of 81 patients who were available for evaluation. For tumor-infiltrating lymphocytes (TIL), 22 out of 76 patients were confirmed with TIL in the pathologic review. Acral lentiginous melanoma was the most common type, followed by nodular melanoma, superficial spreading melanoma, and lentigo maligna melanoma. Univariate analysis for overall survival of melanoma revealed that thickness of tumor, the presence of ulceration, the presence of tumor-infiltrating lymphocytes, clinicopathological subtype, and clinical stage have a tendency for a poorer prognosis. Multivariate analysis demonstrated that advanced stages (III and IV) and tumor thickness were the independent risk factors for poor prognosis. CONCLUSION: Few similar large studies have been conducted to assess the prognostic factors of melanoma in Korea. Therefore, further prospective studies are needed to assess the biological behavior of malignant melanoma, of which the incidence has been steadily increasing in Korea.