Epstein-Barr virus-associated gastric carcinoma in southern India: A comparison with a large-scale Japanese series

Epidemiological and clinicopathological features of Epstein-Barr virus (EBV) associated gastric carcinoma was compared in India and Japan, two countries differing markedly in gastric cancer incidence. Using in situ hybridization assay, the presence of EBV-encoded small RNA (EBER) was examined in 215, and 2,011 gastric cancer cases in Kerala, India, and Japan, respectively. Ten cases (5%), all males, in the Indian series were EBER-positive. This frequency was similar to that in the Japanese series (6.2%). As was the case with Japanese series, the EBV-associated gastric carcinoma in the Indian series was observed most frequently in the middle part of the stomach (1 in antrum, 4 in middle part, 2 in cardia, and 3 unknown), and, histologically, the diffuse type Lauren's classification (8 cases) was more common than the intestinal type (2 cases). Virus subtyping by PCR-RFLP revealed that all of the 10 EBV strains isolated from the EBER-positive Indian cases were subtype A, and wild-type F for Bam HI F region. In Bam HI I region, 8 cases were type C and the remaining 2 cases were type D. In either series, there was no significant difference in the frequency of tumors with p53 overexpression between EBER-positive and -negative cases. However, the proportion of cells with p53 overexpression in EBER-negative tumors was significantly higher than that in EBER-positive tumors regardless of histological type in both series. In conclusion, the frequency and major clinicopathological features of EBV-associated gastric carcinoma in south India were similar to those observed in Japanese series although gastric cancer incidence in these two countries differs markedly.     

Primary cutaneous peripheral T-cell lymphoma with a late relapse solely in the ileum mimicking monomorphic epitheliotropic intestinal T-cell lymphoma

Background

Primary cutaneous peripheral T-cell lymphomas (PC-PTCLs) are classified into mycosis fungoides (MF) and other rare specific types; and those do not fit into any specific entities are designated as PTCL, not otherwise specified (NOS), an aggressive neoplasm. Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is an aggressive primary intestinal T-cell lymphoma with enteropathy in the non-neoplastic mucosa. We report a rare case of PC-PTCL-NOS with a late relapse solely in the ileum after complete remission. We discuss the importance of evaluating enteropathy, megakaryocyte-associated tyrosine kinase (MATK) immunostaining, and the implication of clonal relationship of metachronous lymphomas.

Absence of latent Epstein-Barr virus in thymic epithelial tumors as demonstrated by Epstein-Barr-encoded RNA(EBER) in situ hybridization

BACKGROUND: Several studies have established that Epstein-Barr virus (EBV) is associated with lympho-proliferative disorders such as Burkitt's lymphoma and Hodgkin's disease. EBV is also present in undifferentiated nasopharyngeal carcinomas and in tumors of similar morphology (lymphoepithelioma-like carcinomas) arising in a variety of organs, predominantly in stomach, salivary gland and thymus. As reports of EBV-positive thymic epithelial tumors (TET) have been divergent and as different methods have been used to detect EBV, the aim of this study was to investigate the possible role of EBV in TET of Danish patients. MATERIAL AND METHODS: Archival material of 157 cases of TET (105 thymomas and 52 thymic carcinomas, including 4 lymphoepithelioma-like thymic carcinomas (LELTC)) was analyzed for EBV by applying a sensitive and specific method for detecting latently EBV-infected cells (in situ hybridization for EBV-encoded RNA (EBER)). RESULTS: All investigated cases were EBER negative. CONCLUSIONS: EBV does not seem to be implicated in the pathogenesis of TET. However, a review of the literature showed that 28% of LELTC were EBER ISH positive. As they occurred in young people (mean 18 years), at an age when the patients were susceptible to infection by EBV, it is suggested that EBV merely acts as an innocent bystander.     

Epstein‐Barr virus and the pathogenesis of Burkitt's lymphoma: More questions than answers

Burkitt's lymphoma (BL) was first described as a clinical entity in children in Central Africa by Denis Burkitt in 1958. The particular epidemiological features of this tumor initiated the search for a virus as the causative agent and led to the discovery of Epstein‐Barr virus (EBV) by Epstein and coworkers in 1964. It became apparent in the seventies and eighties that the tumor is not restricted to Central Africa, but occurs with lesser incidence all over the world (sporadic BL) and is also particularly frequent in HIV infected individuals, and that not all BL cases are associated with EBV: about 95% of the cases in Central Africa, 40 to 50% of the cases in HIV‐infected individuals and 10 to 20% of the sporadic cases harbour the viral information and express at least one viral antigen (EBNA1) and a number of non‐coding viral RNAs. In contrast, all BL cases regardless of their geographical origin exhibit one of three c‐myc/Ig chromosomal translocations leading to the activation of the c‐myc gene as a crucial event in the development of this disease. Although epidemiological evidence clearly points to a role of the virus in the African cases, the role of EBV in the pathogenesis of BL has remained largely elusive. This review summarizes current concepts and ideas how EBV might contribute to the development of BL in the light of the progress made in the last decade and discusses the problems of the experimental systems available to test such hypotheses. © 2008 Wiley‐Liss, Inc.     

The efficacy of EBER in situ hybridization (ISH) stain in PTLD (malignant diffuse large B-cell lymphoma) about 4 years after ABO-incompatible kidney transplantation: a case report

Post-transplant lymphoproliferative disease (PTLD) is a well-known late complication of organ transplantation which incidence has increased after the introduction of more powerful immunosuppressive agents. A 58-year-old man performed ABO-incompatible living kidney transplantation in June, 2008. At 3 years and 9 months after the transplantation, the patient complained of general fatigue and dyspnea and was hospitalized with renal dysfunction. The clinical data in hospital showed acute rejection, but soluble IL-II exceeded 21700U/ml, and HE staining kidney graft showed a massive infiltration of atypical lymphocytes. Atypical lymphocytes were positive for L-26 and negative for CD3 immunochemical stein, and the EBER in situ hybridization stain for EBV was negative in renal graft. We diagnosed diffuse large B-cell lymphoma in the kidney graft. However, he died due to multiple organ failure (MOF). We described a fatal case of diffuse large B-cell lymphoma without EBV infection occurring 3 years 9 months after ABO-incompatible kidney transplantation. Unfortunately, post-mortem autopsy using EBER-ISH stain does not show whether EB virus infection was a cause.     

Analysis of single EBER-positive and negative tumour cells in EBV-harbouring B-cell non-Hodgkin lymphomas.

In situ hybridization for Epstein-Barr virus (EBV) encoded small nuclear RNAs (EBERs) is the method of choice for the detection of EBV infection at the single cell level. With the application of this technique it was shown that non-Hodgkin's lymphomas of B-cell type may be associated with an EBV infection of tumour cells. Interestingly, in many EBV-positive cases, only a proportion of the tumour cell population has been found to be EBER-positive. To clarify whether EBV is absent or whether EBER gene expression is downregulated in EBER-negative tumour cells, single EBER-positive and negative tumour cells were isolated from paraffin sections from four B-cell non-Hodgkin's lymphoma cases with partial EBER expression in the neoplastic cells. These single cells were then screened for the presence of EBV DNA by a nested single cell PCR. EBV DNA was undetectable in all but one of the 86 EBER-negative cells, whereas in the EBER-positive cells EBV-specific DNA amplificates could be generated following single cell PCR. This finding prompts the conclusion that the inability to detect EBERs in a proportion of tumour cells is not due to a down-regulation of gene expression but to a real absence of EBV from these cells. This partial absence of EBV is thought to be caused by a loss of the EBV episomes during cell division, rather than by infection of only a proportion of the tumour cells.     

Epstein-Barr病毒EBER基因及其生物学特性研究进展

Epstein-Barr病毒（EB病毒）与传染性单核细胞增多症、继发性噬血细胞性淋巴组织细胞增生症和鼻咽癌等相关,是重要的肿瘤相关病毒.EBERs是EB病毒潜伏感染的细胞内数量最多的病毒转录产物,可能在潜伏感染及细胞转化中发挥重要的作用.此文综述了EBER基因变异及EBERs的生物学特性.     

头颈部淋巴结转移性癌中EBER1的原位杂交检测

本研究对包括鼻咽癌７例，涎腺恶性淋巴上皮病４例和口腔各部位不同分化的鳞状细胞癌５例在内的１６例肿瘤的原发灶和其淋巴结转移灶中的ＥＢＥＲ１进行了原位杂交检测，旨在揭示头颈部转移性癌中ＥＢＶ阳性表达在判断其原发肿瘤来源中的意义。结果表明：在头颈部淋巴结转移性癌中发现非角化型的癌并伴有ＥＢＥＲ１阳性者，可提示其原发灶可能来自于鼻咽癌和涎腺恶性淋巴上皮病。