Association between epstein barr virus and tongue squamous cell carcinoma in iranian patients

Detection of Epstein-Barr virus in oral squamous cell carcinoma suggests its involvement in the carcinogenesis of oral cavity. But, there are few studies on the incidence of EBV genome in squamous cell carcinomas at specific locations in the oral cavity like tongue and with different tumor progression. In this study the presence of EBV genome in tongue Squamous Cell Carcinoma (TSCC) in Iranian patients were investigated. Accordingly, a total of 94 cases with TSCC were firstly analyzed for the presence of viral genome through Nested PCR. Patients were divided into different groups based on their gender and the size, nodal involvement, grade and stage of their tumor. Results showed the presence of EBV genome in 72.3% of TSCCs with no significant difference between two genders, although slightly higher in females. Interestingly, PCR products of EBV genome showed a statistically significant higher distribution in TSCCs at IVa stage (p = 0.04), while a considerable low involvement of EBV genome was seen in T1-sized tumors. The result of this study further emphasizes the role of EBV in oral SCCs – mainly at tongue. This is the first investigation to clarify the association between EBV genome and different tumor size and stage in TSCCs; however, more studies in different regions and larger populations should be performed to be able to draw a firmed conclusion.     

Coinfection with epstein barr virus in north Indian patients with HIV/AIDS

Acquired immunodeficiency syndrome (AIDS) has emerged as a serious health problem in India. Although tuberculosis appears to be the commonest opportunistic infection, studies pertaining to opportunistic viruses are scant In the present study co infection with EBV was evaluated in patients with AIDS using a highly sensitive polymerase chain reaction besides anti Zebra antibody assays for diagnosis of an active EBV infection in 37 patients of full-blown AIDS and 32 healthy seropositives. Thirty healthy laboratory workers were used as controls. Out of 37 patients with AIDS, 12 were positive for anti Zebra antibodies and 23 were positive for EBV by the PCR reaction. Out of the 32 seropositives, 3 were positive for anti Zebra antibodies and 4 were positive by PCR assay. The difference between seropositives and AIDS was significant (p < .05). None of the controls were positive for an active EBV infection. It is concluded that active EBV infection is an important co infection in patients with AIDS and may contribute significantly to morbidity and mortality in these patients.     

Biliary lymphoepithelioma-like carcinoma not associated with Epstein-Barr virus

We report the case of a 64-year-old man who presented with a hepatic mass and macronodular cirrhosis. The pathologic findings revealed a lymphoepithelioma-like carcinoma arising in the hepatobiliary tract that was morphologically identical to nasopharyngeal undifferentiated carcinoma. However, this tumor was not associated with Epstein-Barr virus infection in molecular studies. Macronodular cirrhosis associated with hepatitis C virus was present in the background liver.     

The fibrotic focus in advanced colorectal carcinoma: a hitherto unrecognized histological predictor for liver metastasis

 A fibrotic focus (FF) is a clearly defined area consisting of fibroblasts and/or collagen fibres arranged in irregular or storiform patterns within tumours. We looked to see whether FF in advanced colorectal carcinoma was associated with distant organ metastasis especially to the liver. The correlation between FF and the presence of synchronous or total (synchronous and/or metachronous) liver metastasis and tumour recurrence was assessed in 77 patients with Dukes B and C advanced colorectal carcinoma treated by resection. The median follow-up period was 21 months. In multivariate analysis, FF significantly increased the relative risk (RR) of synchronous liver metastasis (RR=4.9, P<0.05) and total liver metastasis (RR=4.6, P<0.05). FF also increased the RR of tumour recurrence (RR=2.4), but the increase was not statistically significant. FF is a newly recognized histological indicator of liver metastasis in advanced colorectal carcinoma. Received: 26 March 1998 / Accepted: 20 July 1998     

肺淋巴上皮瘤样癌与EB病毒的相关性

目的为阐明肺淋巴上皮瘤样癌（ｌｙｍｐｈｏｅｐｉｔｈｅｌｉｏｍａ－ｌｉｋｅｃａｒｃｉｎｏｍａ，ＬＥＬＣ）与ＥＢ病毒（ＥＢＶ）的关系。方法对３０例肺ＬＥＬＣ和１９例肺非ＬＥＬＣ的石蜡包埋组织，采用原位杂交、免疫组化技术检测ＥＢＶ的存在情况及其基因表达特征。结果肺ＬＥＬＣ中原位杂交ＥＢＶ小ＲＮＡ（ＥＢＥＲｓ）阳性率为９３．３％（２８／３０）；而免疫组化潜在膜蛋白（ｌａｔｅｎｔｍｅｍｂｒａｎｅｐｒｏｔｅｉｎ，ＬＭＰ１）阳性率分别为５３．３％（１６／３０）和２３．３％（７／３０）；１９例病毒衣壳抗原（ｖｉｒｕｓｃａｐｓｉｄａｎｔｉｇｅｎ，ＶＣＡ）阳性率为２３．３％（７／３０）；１９例非ＬＥＬＣ肺癌中原位杂交检测ＥＢＥＲｓ、免疫组化检测ＬＭＰ１均为阴性。结论肺ＬＥＬＣ与ＥＢＶ密切相关，ＥＢＶ可能在肺ＬＥＬＣ发生发展中起重要的作用；ＥＢＶ在肺ＬＥＬＣ中主要以潜伏状态存在，只有少量病毒进入溶解周期。     

肝细胞性淋巴上皮瘤样癌3例及文献复习

目的探讨肝细胞性淋巴上皮瘤样癌的临床病理学特点。方法通过HE、免疫组化染色对3例肝组织中肝细胞性淋巴上皮瘤样癌进行形态学观察。结果瘤细胞异型明显,呈小灶状分布,细胞呈多边形,核居中央,有一清楚核仁,细胞质丰富,嗜酸性,可见细小颗粒,易见核分裂象。肿瘤间质内见大量成熟的淋巴细胞浸润,且分散在瘤细胞之间。3例中肿瘤细胞CK7、Hepatocyte、EB（-）,CK8、AFP（＋）,而间质中淋巴细胞CIM5（＋）、小B淋巴细胞CD20（＋）、小T淋巴细胞CD45RO（＋）。结论肝细胞性淋巴上皮瘤样癌是一种少见的肝上皮源性恶性肿瘤,其诊断主要依靠组织病理学和免疫组化标记。     

Detection of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the lung.

A case of lymphoepithelioma-like carcinoma of the lung is reported in a Chinese patient with serologic evidence of previous Epstein-Barr (EBV) infection. EBV genomes were detected in the tumor using polymerase chain reaction (PCR) and in situ hybridization (ISH) from formalin-fixed, paraffin-embedded tissue blocks. The use of both techniques afforded the exquisite sensitivity of PCR to detect a few copies of EBV DNA with the ability of ISH to precisely localize EBV to the carcinoma, but not to the lymphoid stroma. These findings support a potential oncogenic relationship between EBV and lymphoepithelioma-like carcinoma of the lung.     

腮腺淋巴上皮瘤样癌与EB病毒感染的关系

目的：研究ＥｐｓｔｅｉｎＢａｒｒ 病毒（ＥＢＶ）与腮腺淋巴上皮瘤样癌（ｌｙｍｐｈｏｅｐｉｔｈｅｌｉｏｍａｌｉｋｅｃａｒｃｉｎｏｍａ,ＬＥＬＣ）的关系,并检测瘤细胞内ＥＢＶ 基因编码产物。方法：作者收集了中山医科大学所属病理科１９８６ 年１ 月至１９９５ 年１２ 月间３２ 例腮腺ＬＥＬＣｓ．。３２ 例ＬＥＬＣ石蜡包埋标本再次切片。采用免疫组化和原位核酸杂交法检测瘤细胞内ＥＢＶ 基因表达产物。结果：（１） 在１２５例腮腺癌中有３２ 例淋巴上皮瘤样癌,占总病例的２５－６％ （３２／１２５） 。（２）所有３２ 例腮腺ＬＥＬＣ组织中均有数量不等的ＥＢＮＡ１ 和ＥＢＥＲｓ 阳性瘤细胞。（３）２７ 例ＬＥＬＣ 组织中部分瘤细胞表达ＬＭＰ１ 。（４） 所有标本中均未见ＺＥＢＲＡ 阳性细胞。（５）３２例腮腺ＬＥＬＣ组织中ＥＡＤ、ＶＣＡ和ＭＡ的阳性表达率分别为７１－９ ％（２３／３２） 、６８－８ ％（２２／３２） 和１２－５％ （４／３２） 。结论：（１） 在鼻咽癌高发的广州地区,腮腺ＬＥＬＣ的发病率也较高。（２）腮腺ＬＥＬＣ 组织中均有ＥＢ病毒感染。（３）ＥＢ病毒在腮腺ＬＥＬＣ的感染主要为潜伏Ⅱ型,即表达ＥＢＮＡ１ 、ＥＢＥＲｓ 和ＬＭＰ１     

Presence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the middle ear.

AIM: To examine the association of Epstein-Barr virus (EBV) with carcinoma of the ear. METHODS: Five non-keratinising squamous cell carcinomas and two undifferentiated carcinomas of the ear were examined. In situ hybridisation was used to localised EBV-encoded RNAs (EBER). Immunohistochemical methods to detect LMP-1 and EBNA2 were performed in the EBER positive cases. RESULTS: Two cases were EBER positive, including one non-keratinising and one undifferentiated carcinoma. Both showed identical morphology to those arising from the nasopharynx, with abundant lymphoid stroma. They were both negative for LMP-1 and EBNA2. CONCLUSIONS: EBV associated carcinoma with the morphology of lymphoepithelioma can also arise from the middle ear.     

Hepatocellular carcinoma associated with focal nodular hyperplasia

We describe a hepatocellular carcinoma partially surrounded by focal nodular hyperplasia in a 65-year-old female patient. In order to clarify the relationship of the hepatocellular carcinoma and the adjacent focal nodular hyperplasia, clonal analysis was conducted. The clonal analysis was based on the methylation pattern of the polymorphic X-chromosome-linked androgen receptor gene (HUMARA). The allelic bands from the amplification of the focal nodular hyperplasia and of the hepatocellular carcinoma showed a significant reduction in the intensity of one of the two alleles as compared with two alleles of equal intensity in the buff coat after HhaI digestion, which indicated that these two parts were monoclonal. However, the inactivated allele in the focal nodular hyperplasia and that in the hepatocellular carcinoma were not identical. Therefore, the focal nodular hyperplasia and hepatocellular carcinoma probably derived from the clonal expansion of two different clones.     

Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China

Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in southern China, we found that 32 cases could meet the criteria for lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ hybridization and immunohistochemistry techniques to detect the EBV-encoded small nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the 32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive signals in carcinoma cells. The results demonstrate that there is a close relationship between EBV infection and pulmonary LELC. EBV infection may have an essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is the main status in pulmonary LELC except for individual EBV entering into a lytic cycle.     

An unusual variant of T-CLL: evidence for the existence of a hitherto unrecognized T cell subset.

A case of T-cell chronic lymphocytic leukaemia (T-CLL) with an unusual mature membrane phenotype: E+, CD3+, CD4+, CD8-, M1+, Leu-15+, Fc gamma+, is described. The cells were large granular lymphocytes with slight immature features. Functionally these cells lacked helper, suppressor and NK activity but possessed normal levels of K activity. These findings demonstrate several features not previously described in T-CLL: the coexpression of the antigens detected by T4, M1 and Leu-15 the presence of Fc gamma receptors on CD4+ lymphocytes and the lack of NK activity in M1+, Fc gamma+ cells. This study broadens the known heterogeneity of T-CLL and suggests the existence of a hitherto unrecognized normal T-lymphocyte subset with the same functional and phenotypic characteristics as in the case described here.     

Hepatocellular carcinoma associated hemolytic uremic syndrome unrelated to chemotherapy.

A 67-year-old man, diagnosed as hepatocellular carcinoma by percutaneous needle aspiration biopsy of liver mass, presented microangiopathic hemolytic anemia, thrombocytopenia and renal failure from the early phase of the illness. We could establish the diagnosis of cancer-associated hemolytic uremic syndrome which was unrelated to chemotherapy clinically. This is a rare case reported in adult hepatoma patients.     

胃EB病毒阳性淋巴上皮瘤样癌伴B淋巴细胞单克隆性增生一例

报道1例罕见胃EB病毒阳性淋巴上皮瘤样癌合并B淋巴细胞单克隆性增生,并复习相关文献。患者为男性75岁,胃底贲门见一溃疡型肿块。镜下观察:肿瘤以推挤性生长为主,侵及胃壁深肌层。肿瘤组织中淋巴上皮间质明显多于肿瘤细胞,肿瘤细胞间质淋巴细胞背景中部分为B淋巴细胞构成,周围可见淋巴上皮病变。EB病毒原位杂交显示:癌细胞阳性。分子病理显示B细胞IgH-DH克隆性基因重排。最终诊断为:胃EB病毒阳性淋巴上皮瘤样癌伴淋巴样间质内B细胞单克隆性增生。     

Hepatocellular carcinoma: an update.

Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.     

Cribriform adenocarcinoma of the tongue: a hitherto unrecognized type of adenocarcinoma characteristically occurring in the tongue

AIMS: We report a review of our institutional and consultation files in order to select cases of hitherto unrecognized type of adenocarcinoma occurring in the tongue. MATERIALS AND RESULTS: Eight cases of a characteristic adenocarcinoma of the tongue resembled solid and follicular variants of the papillary carcinoma of the thyroid. All the tumours were unencapsulated and were divided by fibrous septa into lobules. Major parts of the lesions were composed of areas with solid and microcystic growth patterns. The most striking cytological feature was that the tumour nuclei were pale-staining with a 'ground glass' quality, and they often appeared to overlap. Immunohistochemically, the tumours expressed cytokeratin and S100 protein and, focally, actin; thyroglobulin was negative. Ultrastructurally the cells had clefted nuclei, and the cytoplasm contained a few mitochondria, lysosomes and Golgi apparatus. Many tumour cells had combined features of both myoepithelial and secretory differentiation-well formed microvilli on their apical borders and bundles of microfilaments. At first presentation, all eight patients had metastases in the regional neck lymph nodes, but all are alive 2-6 years after the initial excision and irradiation. CONCLUSION: We describe a distinctive type of adenocarcinoma of the tongue, for which we propose the name cribriform adenocarcinoma of the tongue (CAT). CAT usually presents with metastases in the neck lymph nodes at the time of presentation. We hypothesize that the tumour might arise from the thyroglossal duct anlage.