Epstein-Barr virus associated lymphoepithelioma-like carcinoma at the lesser curvature of the upper gastric body: a Case Report / El virus de Epstein-Barr asociado al carcinoma de tipo linfoepitelioma en la curvatura menor de la parte superior del cuerpo gástrico: Reporte de Caso

Lymphoepithelioma-like gastric carcinoma (LELGC) is a rare neoplasm of the stomach with dense lymphocytic infiltration. More than 80% of LELGCs are positive for the Epstein-Barr virus (EBV). Here, we report a 64-year old Chinese man with swallowing discomfort while eating food. Endoscopy and computed tomography both showed a submucosal lesion at the lesser curvature of the upper gastric body. The first diagnostic impression was a gastrointestinal stromal tumour. Subsequently, the patient received a wedge resection of the stomach. On histopathological examination, the tumour was found to consist of small nests of neoplastic cells within dense lymphocytic infiltration. Additionally, most of the neoplastic cells were positive for cytokeratin and Epstein-Barr virus-encoded RNA (EBER). Subsequently, the diagnosis of LELGC was made. We believe that physicians should be aware of the diagnosis of submucosal gastric lesions, particularly in older male patients.

El carcinoma gástrico de tipo linfoepitelioma (CGLE) es una neoplasia rara del estómago con una infiltración linfocítica densa. Más del 80% de los CGLEs son positivos al virus de Epstein-Barr (EBV). Aquí reportamos el caso de un paciente chino de 64 años, que sentía malestar al efectuar la deglución de alimentos. Tanto la endoscopia como la tomografía computarizada mostraron una lesión submucosa en la curvatura menor de la parte superior del cuerpo gástrico. La primera impresión diagnóstica fue de un tumor del estroma gastrointestinal Posteriormente, al paciente se le hizo una resección en cuña del estómago. En el examen histopatológico, se halló que el tumor consistía de pequeños nidos de células neoplásicas dentro de una infiltración linfocítica densa. Además, la mayoría de las células neoplásicas eran positivas a la citoqueratina y al ARN codificado por el virus de Epstein-Barr (EBER). Posteriormente, se realizó el diagnóstico de CGLE. Creemos que los médicos deben tomar conciencia del diagnóstico de las lesiones submucosas gástricas, especialmente en los pacientes mayores hombres.

Human Papilloma Virus: Prevalence, distribution and predictive value to lymphatic metastasis in penile carcinoma

Objectives To evaluate the prevalence, distribution and association of HPV with histological pattern of worse prognosis of penile cancer, in order to evaluate its predictive value of inguinal metastasis, as well as evaluation of other previous reported prognostic factors. Material and Methods Tumor samples of 82 patients with penile carcinoma were tested in order to establish the prevalence and distribution of genotypic HPV using PCR. HPV status was correlated to histopathological factors and the presence of inguinal mestastasis. The influence of several histological characteristics was also correlated to inguinal disease-free survival. Results Follow-up varied from 1 to 71 months (median 22 months). HPV DNA was identified in 60.9% of sample, with higher prevalence of types 11 and 6 (64% and 32%, respectively). There was no significant correlation of the histological characteristics of worse prognosis of penile cancer with HPV status. Inguinal disease-free survival in 5 years did also not show HPV status influence (p = 0.45). The only independent pathologic factors of inguinal metastasis were: stage T ≥ T1b-T4 (p = 0.02), lymphovascular invasion (p = 0.04) and infiltrative invasion (p = 0.03). conclusions HPV status and distribution had shown no correlation with worse prognosis of histological aspects, or predictive value for lymphatic metastasis in penile carcinoma. .

Carcinoma de ano, pene, vulva y vagina: ¿son enfermedades de transmisión sexual? / Anogenital neoplasms: are sexually transmitted diseases?

Introducción: La infección por virus papiloma humano (VPH) sería factor causal de cánceres de ano, pene, vulva y vagina. Objetivo: Analizar la evidencia actual en cuanto a infección por VPH y su rol carcinogénico en estas neoplasias. Metodología: Búsqueda de la literatura para identificar artículos sobre la transmisión sexual como factor de riesgo en cánceres anogenitales. Resultados: En lesiones premalignas y malignas anogenitales se encuentra en gran frecuencia el DNA de VPH, especialmente tipo 16. Se ha demostrado que la vacunación contra VPH previene el desarrollo de lesiones preinvasoras anales; en cambio, ni la vacuna ni la circuncisión parecen ser factores protectores contra cáncer de pene. Discusión: No hay estudios prospectivos que permitan establecer una relación causal entre VPH y cánceres anogenitales, lo que impide la elaboración de estrategias de prevención. El manejo de ciertos factores de riesgo sugeridos previamente en la literatura no reduce el riesgo de cáncer anogenital.

Introduction: Human papillomavirus (HPV) infection has been suggested as a causal factor of anal, penile, vulvar and vaginal cancers. Objective: To analyze current evidence about HPV infection and its carcinogenic role in these neoplasms. Methodology: Literature search to identify articles about sexual transmission as a risk factor in anogenital cancers. Results: In premalignant and malignant anogenital lesions, an important presence of HPV DNA is often found, specially type16. It has been demonstrated that HPV vaccine prevents premalignant anal lesions; however, this vaccine and circumcision do not seem to be protective against penile cancer. Discussion: There are no prospective studies that had established a causal relationship between HPV and anogenital cancers. This keeps off the development of adequate prevention strategies. Management of certain previously suggested risk factors do not reduce the risk of anogenital cancer.

Identificación de asociaciones clínico-patológicas e hipermetilación de genes supresores de tumores en cáncer gástrico difuso a través de análisis de Hierarchical clustering / Hierarchical clustering analysis to detect associations between clinical and pathological features of gastric tumors and hypermethylation of suppressor genes

Background:Methylation is an inactivation mechanism for tumor suppressor genes, that can have important clinical implications. Aim: To analyze the methylation status of 11 tumor suppressor genes in pathological samples of diffuse gastric cancer. Material and methods: Eighty three patients with diffuse gastric cancer with information about survival and infection with Epstein Barr virus, were studied. DNA was extracted from pathological slides and the methylation status of genes p14, p15, p16, APC, p73, FHIT, E-caderin, SEMA3B, BRCA-1, MINT-2 y MGMT, was studied using sodium bisulphite modification and polymerase chain reaction. Results were grouped according to the methylation index or Hierarchical clustering (TIGR MultiExperiment Viewer). Results: Three genes had a high frequency of methylation (FHIT, BRCA1, APC), four had an intermediate frequency (p15, MGMT, p14, MINT2) and four had a low frequency (p16, p73, E-cadherin, SEMA3B). The methylation index had no association with clinical or pathological features of tumors or patients survival. Hierarchical clustering generated two clusters. One grouped clinical and pathological features with FHIT, BRCA1, and APC and the other grouped the other eight genes and Epstein Barr virus infection. Two significant associations were found, between APC and survival and p16/p14 and Epstein Barr virus infection. Conclusions: Hierarchical clustering is a tool that identifies associations between clinical and pathological features of tumors and methylation of tumor suppressor genes.

Inestabilidad microsatelital en lesiones preneoplásicas y neoplásicas del cuello uterino: Correlación con el genotipo del virus papiloma humano / Microsatellite instability and human papilloma virus genotypes in preneoplastic and neoplastic uterine cervix lesions

Background: The association between some specific human papilloma virus (HPV) types and cervix cancer is well known. However, the genetic conditions that favor the development of cervical cancer are less well known. Aim: To determine the presence of satellite instability (MSI) in preneoplastic and neoplastic lesions of the cervix and correlate these findings with HPV genotypes. Material and methods: Biopsy samples of cervical lesions were studied. Sixteen had low grade lesions, 22 had high grade lesions and 28 had an epidermoid cancer. Viral types were identified with polymerase chain reaction, dot-blot hybridization and restriction fragment length polymorphism. MSI was determined using a panel of eight highly informative microsatellites. Results: Microsatellite instability in at least one locus was observed in 91, 56 and 69 percent of low grade lesions, high grade lesions and epidermoid carcinomas, respectively. MSI-High grade, MSI-Low grade instability and microsatellite stability were observed in 5, 60 and 46 percent of samples, respectively. Two of three samples with high grade instability had HPV 52 genotype. Other viral subtypes had frequencies that ranged from 78 percent to 100 percent, with the exception of HPV16 that was present in only 53 percent of samples with low grade instability. Conclusions: Two thirds of biopsy samples from cervical lesions had MSI, mechanism that can be involved in the first stages of cervical carcinogenesis. The low frequency of high grade instability, its association with HPV52 and the low frequency of HPV16 in samples with low grade instability, suggest different coadjutant mechanisms in cervical carcinogenesis

Carcinoma gástrico de tipo linfoepitelioma: variante inusual en muñón post-gastrectomía / Lymphoepithelioma-like gastric carcinoma: unusual variant in postgastrectomy stump

El carcinoma de tipo linfoepitelioma, indiferenciado con estroma linfoide o medular, constituye un 3,8% de los carcinomas gástricos. Microscópicamente es similar a linfoepiteliomas de otras localizaciones, tiene crecimiento expansivo y mejor pronóstico que otros tipos histológicos. Se postula probable relación con el virus de Epstein Barr. Una mujer de 56 años gastrectomizada por cáncer hacía 31 años (Billroth) mostró en la endoscopía lesión ulcerada próxima a neboca. Se biopsió con resultado positivo y se realizó gastrectomía. Se recibió pieza que incluía muñón gástrico, yeyuno anastomosis, epiplón y glanglios. Presentaba lesión sobreelevada, ulcerada, de 4,5 cm ubicada en cara anterior a 1,5 cm de neoboca. Se efectuó fijación en formol buffer, procesamiento según métodos habituales y coloración con Hematoxilina-Eosina. Se realizaron técnicas de Inmunohistoquímica para CKAE1-AE3, EMA, CEA, CD45, CD20, CD3 y CD45Ro, y de PCR para virus de Epstein Barr. Microscópicamente estaba constituida por una proliferación expansiva de células poligonades con citoplasma ligeiramente eosinófilo y núcleos vesiculares, dispuestas en pequeños nidos o asiladas, positivas para CKES1-AE3, EMA y CEA, con denso infiltrado linfoide maduro, de disposición folicular y difuso, positivo para CD45, CD45Ro, CD3 y CD20. La técnica de PCR fue positiva. Éste es el primer caso de este tipo registrado en nuestro servicio desde 1989. Además de las características peculiares de esta variedad, cuyo diagnóstico diferencial debe haceres con los linfomas. es relevante su origen en muñón gástrico, donde esta complicación aparece con cifras variables, estando el riesgo vinculado al tipo de cirgía y tiempo transcurrido.

Detection of human papillomavirus in epithelial lesions of the conjunctiva

CONTEXT: Many factors like exposure to UV radiation, climatic conditions, genetic predisposition, immunological state and, more recently, the presence of HPV have been implicated in the genesis of some lesions of the conjunctiva, especially the carcinoma. OBJECTIVE: To evaluate the presence of HPV DNA in acquired lesions of the conjunctiva and in normal mucosa. TYPE OF STUDY: Cross-sectional study. SETTING: A public university referral center (the Ophthalmology Service of the A.C. Camargo Hospital - A. Prudente Foundation, Sao Paulo). PARTICIPANTS: Thirty patients with acquired lesions of the conjunctiva and 60 matched controls (by age and sex) were evaluated in this study, from June 1993 to March 1995. PROCEDURES: The detection of HPV DNA in the normal conjunctiva and in acquired lesions was done by the PCR technique and dot blot hybridization. The material was collected by scraping the normal mucosa and the surface of the lesions. A fragment of fresh frozen tissue and paraffin embedded specimens of each lesion were also included. MAIN MEASUREMENTS: The association between the HPV infection and the presence or absence of conjunctival lesions. RESULTS: Sequences of HPV DNA were detected in 4 of the 31 lesions evaluated (12.9 percent) and in the healthy mucosa of one individual of the control group (1.6 percent). HPV type 16 was detected in 2 carcinomas and in the normal mucosa of one individual of the control group. HPV type 11 was demonstrated in 2 papillomas of one patient with lesions in both eyes. CONCLUSIONS: The low frequency of HPV DNA found in the lesions of this sample and the detection of the viral genome in the normal mucosa indicate that there is a weak possibility of association between HPV infection and the carcinoma of the conjunctiva

Detección del virus papiloma humano en lesiones cancerosas orales en la ciudad de Córdoba / Human papillomavirus detection in oral cancer lesions in the city of Córdoba

El cáncer oral es un proceso que involucra diferentes factores etiológicos y mecanismos, a luz de los conceptos actuales de cocarcinogénesis. Existen evidencias histológicas y de hibridación que sugieren la participación del virus papiloma humano (HPV) en la carcinogénesis oral. La Cátedra de Anatomía Patológica de la Facultad de Odontología de la Universidad Nacional de Córdoba recibe aproximadamente el 20 por ciento de los pacientes con lesiones cancerosas orales en esta ciudad. En el período comprendido entre los años 1992-1997 fueron examinadas 1950 biopsias, 4,77 por ciento (93/1950) de ellas fueron diagnosticadas como neoplasias malignas, de éstas el 79,57 por ciento (74/93) fueron carcinomas. Treinta y tres carcinomas orales (44,6 por ciento; 33/74) fueron seleccionados al azar e incluí dos en el estudio. Se incluyeron 33 extendidos celulares de pacientes con mucosa oral normal. Los materiales fueron estudiados por microscopia óptica y por la técnica de hibridación "in situ" para la detección del DNA de HPV. Los datos fueron analizados mediante el test de chi cuadrado. La prevalencia de HPV entre las 33 muestras casos estudiada fue 27,27 por ciento, 9/33 fueron positivos para HPV en condiciones no estrictas. Un material fue positivo en condiciones estrictas para HPV 16, un carcinoma verrugoso. En las muestras de mucosa oral normal no se detectó HPV. Entre los HPV positivos, 3/9 (33,33 por ciento) fueron carcinomas espinocelulares y 5/9 (55,56 por ciento) carcinomas verrugosos. Uno fue un melanoma. El carcinoma verrugoso fue la neoplasia asociada con más frecuencia a la infección por HPV (x2=20,5; con un nivel de confianza del 95 por ciento); lo que podría sugerir un mayor papel del HPV en la patogénesis del carcinoma verrugoso. La presencia viral encontrada en lesiones cancerosas refuerza la naturaleza multicausal del cáncer oral. El HPV es una circunstancia que incrementa la probabilidad de malignidad, y que cuando se reduce, disminuye la frecuencia de cáncer.