Biomedical subjects

I Anagnostopoulos

Publications and source records attributed to I Anagnostopoulos.

At least 73 records · Page 4Linked to original sources

PubMed1997

Expression of several members of the TNF-ligand and receptor family on tonsillar lymphoid B cells.

Although the expression patterns of the members of the tumour necrosis factor receptor and ligand families have extensively been studied by flow-cytometry on stimulated peripheral blood mononuclear cells (PBMNC), little or no flow-cytometric or immunohistological data exist about their expression in lymphoid tissue. According to the data obtained from stimulated PBMNC, several members of these molecule families (e.g. CD40 ligand [CD40L], CD30, CD27, hOX40) have been considered to be either T-cell restricted or strongly T-cell associated. The present study on samples from palatine tonsils revealed that most of these molecules are also expressed by tonsillar B cells. The additional analysis of the co-expression of these molecules also disclosed the existence of CD40+/CD40L+ and CD27+/CD70+ (CD27L+) lymphoid cells in tonsillar tissue.

Antigens, CD↗

PubMed1997

Uniform expression of cytotoxic molecules in anaplastic large cell lymphoma of null/T cell phenotype and in cell lines derived from anaplastic large cell lymphoma.

We recently provided ample evidence that anaplastic large cell lymphomas of T/null phenotype (T-/null-ALCL) genotypically represent peripheral T cell lymphomas which in up to 90% have a phenotype of cytotoxic cells with expression of granzyme B protein and perforin transcripts. However, the issue of granzyme B expression in T-/null-ALCL is still controversial due to differing results from another laboratory. To verify our earlier immunohistochemical stainings for granzyme B, we looked for granzyme B transcripts by in situ hybridization (ISH). In addition, we investigated our previously analyzed cases by immunohistology (IH) with another antibody (2G9), which reacts with two molecules known to be expressed in cytotoxic cells: T-cell-restricted intracellular antigen (TIA)-1 and granule membrane protein-17 (GMP-17). We also extended our studies to homogenous tumor cell populations provided by ALCL-derived cell lines. As evidenced by ISH, transcripts for perforin, TIA-1 and granzyme B were found in all ALCL-derived cell lines. Similarly, proteins of TIA-1/GMP-17, granzyme B and perforin were expressed in all of these lines as shown by IH. In biopsy specimens, TIA-1/GMP-17 were detected by IH in 14/16 cases of T-/null-ALCL, and granzyme B transcripts were found in 13/13 T-/null-ALCL cases, but not in 6 B-ALCL cases. The detection of granzyme B transcripts yielded results largely identical to those of IH for granzyme B protein, thus confirming our earlier data and suggesting that the regulation of the expression of this molecule largely occurs at the transcriptional level. Our data further confirm the almost uniform expression of cytotoxic molecules in both primary ALCL cases and ALCL-derived cell lines and therefore suggest that the derivation from cytotoxic T cells may be the unifying characteristic for T-/null-ALCL.

Cytotoxicity, Immunologic↗

PubMed1997

[Hodgkin's disease: a mystery is being solved].

The cell lineage derivation and type of proliferation (monoclonal versus polyclonal) of the atypical cells in Hodgkin's Disease (HD) has remained in question up until now. Immunophenotypic studies favoured a lymphoid origin. Molecular biological studies using DNA extracted from whole biopsy material provided inconsistent results, probably due to the rarity of the atypical cells in the affected tissue. Hence the molecular biological studies were extended to the analysis of isolated atypical cells. However, even these single cells studies yielded conflicting results. We therefore have improved the technique of single cell isolation from tissue sections and applied it to 25 cases of classical HD and 11 cases of lymphocyte predominant HD (LPHD). We investigated a total of 1,465 single atypical cells for rearranged Ig variable-region chain (V) genes. In all instances in which the single cell DNA lead to a PCR amplification product, these were found to contain identical rearranged V region genes. All of these V region gene sequences proved to be highly mutated. The coding capacity of the rearranged Ig genes was frequently disrupted in classical HD but rarely in LPHD. The V sequences of the latter histotype showed in addition intra-clonal diversity in the majority of patients whereas this was not seen in all but one case of classical HD. Additionally, in 10 to 20% of classical HD cases T-cell antigens and/or cytotoxic molecules could be demonstrated in the atypical cells. These results indicate that, a) the atypical cells of LPHD are a clonal population of neoplastic germinal centre B cells; b) the atypical cells from 80-90% of classical HD cases represent a clonal expansion of B cells which are related to germinal centre B cells or their progeny; and c) the atypical cells of 10-20% of classical HD may originate from T cells.

Antigens, CD↗

PubMed1997

Molecular biology of Hodgkin's disease.

The mist surrounding the origin and genesis of HRS cells of classical HD is beginning to dissipate. Molecular biological studies of classical HD at the single cell level strongly suggest that the HRS cells in the majority of cases represent a monoclonal outgrowth of late germinal centre B cells that have lost their capacity to express IG through crippling mutations introduced during the germinal centre reaction. Because of the expression of T cell antigens and/or cytotoxic molecules, the HRS cells of a minority of classical HD cases appear to originate from T cells. Under physiological conditions, B cells that are unable to express IG are eliminated by apoptosis. In most B cell derived classical HD cases, the HRS cells have lost their IG gene coding capacity through mutation and should therefore die of apoptosis. Since this usually does not happen, blockade of the apoptotic pathway may be a major event in the pathogenesis of B cell related classical HD. It is tempting to assume that viruses such as EBV, as well as regulator genes that normally monitor the human genome for damaged DNA, such as TP53, might be involved in the postulated hindrance of the apoptotic pathway, leading to the genesis of classical HRS cells.

Chromosome Aberrations↗

PubMed1996

Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules.

To further specify the cellular origin and nature of anaplastic large-cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T-ALCL, at least in terms of cellular origin.

Biomarkers↗

PubMed1996

Comparison of dermatomal SEPs and operative findings in lumbar disc disease.

This report deals with an estimation of the diagnostic value of dermatomal somatosensory evoked potentials (SEPs), by correlating the neurophysiological data to clinical, neuroradiological and operative findings in lumbar disc protrusion. Our material consists of 12, surgically treated patients with lumbar disc protrusion in which diagnostic work up included history, neurological examination, routine lumbar spine films, computerised tomography and MRI of the lumbar spine, in addition to neurophysiological investigation, especially conduction velocity studies, and SEPs recorded by the standard methods, as well as after dermatomal stimulation. The retrospective analysis disclosed a correlation for the SEPs after dermatomal stimulation and surgical findings, in 83% of our cases.

Adult↗

PubMed1996

Lymphocyte predominant Hodgkin's disease--a workshop report. European Task Force on Lymphoma.

Since lymphocyte predominant Hodgkin's disease (LPHD) may comprise more than one entity, diagnostic criteria, clinical features, and treatment strategies are still being controversially discussed. Thus, in December 1994 a multinational project on lymphocyte predominant Hodgkin's disease was initiated by the European Task Force on Lymphoma. This project is aimed at clarifying the clinical and histopathological spectrum of LPHD, as well as its relation to T-cell- rich B-cell lymphoma and classical types of HD. 525 paraffin blocks and clinical data of 478 patients from 16 international centres were submitted. At the Third International Symposium on Hodgkin's Lymphoma in Cologne, 232 of these cases were discussed by an expert panel. The preliminary results are presented here. Most cases of LPHD were reclassified into nodular paragranuloma (NP) and lymphocyte rich classical HD. In both groups, a considerable number of cases with atypical features was observed. Few cases of NHL were found among the cohort. LPHD was generally treated according to common standards for HD. The whole group of LPHD did not have a better prognosis than NS; whereas early stage NP did perform better than early stage NS (data from the German Hodgkin's Lymphoma Study Group). There is however a striking discrepancy between good survival and the frequent relapses observed in NP which needs to be elucidated.

Hodgkin Disease↗

PubMed1996

Epstein-Barr virus in tumours.

The Epstein-Barr virus (EBV) is the best characterized human virus known to infect most people all over the world. In most cases, primary infection with EBV is asymptomatic and the virus persists life-long without causing any disease. The availability of sensitive detection methods, however has led to the identification of a wide array of EBV-associated disease entities. Although nearly 9000 publications have been written since the first description of this virus in 1964, many questions concerning its function and infection patterns remain unanswered. The direct involvement of EBV in the pathogenesis of a disease has only been established for infectious mononucleosis and lymphoproliferative disorders in the setting of congenital or acquired immunodeficiency. Extensive investigations on the role of EBV infection in the pathogenesis of all other EBV-associated lymphoid and epithelial proliferations have led to the conclusion that EBV is not the primary causative agent but it can promote tumour development. Since the early steps in neoplastic development are difficult to assess, further studies are required to clarify the precise role of EBV infection. Furthermore, the clinical significance of the presence of EBV in neoplasia is largely unknown.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Monoclonal antibodies PG-B6a and PG-B6p recognize, respectively, a highly conserved and a formol-resistant epitope on the human BCL-6 protein amino-terminal region.

The human BCL-6 gene, which is rearranged in approximately 30% of diffuse large B cell lymphomas, encodes a 706-amino-acid nuclear protein of the Kruppel-type zinc finger transcription factors mainly expressed in normal germinal center B cells and related lymphomas. Four monoclonal antibodies (PG-B6, PG-B6a, PG-B6p, and PG-B6m), specifically directed against the human BCL-6 protein, were generated by immunizing BALB/c mice with a recombinant protein corresponding to the BCL-6 amino-terminal region (amino acids 3 to 484). The PG-B6 monoclonal antibody reacted with a BCL-6 epitope sensitive to fixatives and preserved in all mammalian species. PG-B6a (a is for avian) recognized the most evolutionarily conserved BCL-6 epitope (expressed in all animal species including avian). PG-B6p (p is for paraffin) recognized a fixative-resistant epitope of BCL-6 that was detectable on paraffin sections after microwave heating in 1 mmol/L EDTA buffer. PG-B6m (m is for mantle) was the least specific monoclonal antibody as, in addition to BCL-6, it reacted with a yet undefined antigen selectively located in the cytoplasm of mantle and marginal zone B cells. All monoclonal antibodies detected strong nuclear expression of BCL-6 in follicular lymphomas, diffuse large B cell lymphomas, Burkitt's lymphomas, and nodular, lymphocyte-predominance Hodgkin's disease. In diffuse large B cell lymphomas, BCL-6 expression was independent of BCL-6 gene rearrangements and did not correlate with expression of other markers or the proliferation index. BCL-6 was not expressed in B-CLL, hairy cell leukemia, mantle-cell- and marginal-zone-derived lymphomas. Labeling of paraffin sections with PG-B6p proved useful for differentiating proliferation centers in B-CLL (BCl-2+/BCL-6-) from trapped germinal centers in mantle cell lymphomas (BCL-2-/BCL-6+) and for identifying neoplastic cells in cases of nodular, lymphocyte-predominance Hodgkin's disease. Because of their high specificity, wide reactivity in humans and animal species including avians (PG-B6a), and suitability for labeling routine paraffin sections (PG-B6p), the reagents described in this paper should prove valuable in both research and diagnostics.

Amino Acid Sequence↗

PubMed1996

Low incidence of Epstein-Barr virus presence in primary cutaneous T-cell lymphoproliferations.

Multiple biopsies taken from 76 European human immunodeficiency virus (HIV)-negative patients with primary cutaneous T-cell lymphoproliferations, including mycosis fungoides (MF), pleomorphic T-cell lymphoma (PMTCL), anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP) were investigated for the presence of Epstein-Barr virus (EBV) through a combined approach. Polymerase chain reaction (PCR) was employed for EBV-DNA detection, in situ hybridization (ISH) for cellular localization of EBV-encoded nuclear RNAs (EBER1 and EBER2) and immediate early Bam H-fragment; lower frame (BHLF) RNA, and immunohistology (IH) for the identification of EBV-encoded latent membrane protein 1 (LMP1) and of nuclear antigen (EBNA) 2 expression. EBV-DNA was detectable by PCR in 15 of 76 cases (19.7%). EBER-ISH combined with IH identified a variable, usually very low, number of infected neoplastic cells in only seven of the 15 EBV-DNA-harbouring cases. This discrepancy between the results obtained with PCR and ISH is apparently caused by the low number of the infected cells per tissue section. The PMTCL entity produced the greatest number of positive cases, whilst ALCL and LyP cases were almost constantly devoid of the virus. BHLF transcripts were not detectable in any case, nor did any of the EBER-positive cells show an LMP1 or EBNA2 expression. These data show that primary cutaneous T-cell lymphoproliferations display an infrequent association with a latent EBV infection and that the pathogenic role of the virus in the positive cases remains obscure as the virus frequently infects only a minority of the atypical cells.

DNA, Viral↗

PubMed1995

Patterns of cytokine gene expression in peripheral T-cell lymphoma of angioimmunoblastic lymphadenopathy type.

Peripheral T-cell lymphoma of angioimmunoblastic lymph-adenopathy type (AILD-TCL) is histologically characterized by a mixed infiltrate of atypical T cells, B cells including B immunoblasts, and plasma cells, as well as eosinophilic granulocytes accompanied by proliferated high endothelial venules, while, clinically, fever and weight loss are often observed. These morphologic and clinical pecularities are widely believed to reflect abnormal patterns of cytokine expression. To evaluate this hypothesis, 11 lymph nodes with AILD-TCL were studied for the presence of tumor necrosis factor-alpha (TNF), lymphotoxin (LT), interleukin-6 (IL-6), and IL-1 beta transcripts by in situ hybridization (ISH) using [35S]-labeled cytokine-specific RNA probes in seven cases subsequent to immunohistology for cell type characteristic antigens. Expression of all four cytokines was strongly enhanced in AILD-TCL when compared with the control groups of lymphoblastic lymphomas and peripheral T-cell lymphomas, other than AILD-TCL. TNF and LT transcripts were present in atypical T cells and in a variable proportion of B immunoblasts in all AILD-TCL cases, whereas IL-6 and IL-1 beta specific transcripts were mainly found in nonlymphoid cells. To verify a possible cytokine expression by Epstein-Barr virus (EBV)-infected cells, which are frequently present in AILD-TCL, the detection of EBV-encoded nuclear RNAs (EBER) was combined with ISH for cytokine transcripts. It became evident that expression of LT and TNF by EBV-infected cells was largely restricted to B immunoblasts, which were only infrequently present in most AILD-TCL cases, whereas the expression of IL-6 was very rare, and IL-1 beta was not found in EBV-infected cells. These data suggest that expression of TNF and LT genes may contribute to the characteristic histologic and clinical features of AILD-TCL and that cytokine expression by EBV-infected cells does not, in most cases, contribute significantly to the overall cytokine expression. Because it has been shown that LT is an autocrine growth factor for EBV-infected B cells, expression of this cytokine could contribute to the proliferation of EBV-infected B cells in AILD-TCL and, in the setting of immunosuppression, may ultimately play a role in the development of B-immunoblastic lymphomas.

Cytokines↗

PubMed1995

Morphology, immunophenotype, and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: implications for the interindividual infection route of Epstein-Barr virus.

The present study was undertaken to unequivocally demonstrate the morphology, immunophenotype, and localization of Epstein Barr virus (EBV)-infected cells as well as the type of infection (latent versus productive) in tonsils of acute infectious mononucleosis. Paraffin sections from nine cases with clinical, serologic, and morphologic evidence of EBV infection were analyzed for the detection of small transcripts, designated EBER1 & 2, and BHLF1 by in situ hybridization (ISH) using nonisotopically labeled probes. ISH was combined with immunohistology, employing a broad panel of antibodies against B-, T-, epithelial-, macrophage-, and follicular dendritic cell (FDC)-antigens. All EBER-positive cells could be identified as lymphocytes, as they did not exhibit any morphologic or immunologic characteristics of epithelial cells, macrophages, or FDCs. A preferential accumulation of EBER-positive cells was noted around crypts, within surface squamous epithelium, and in the surroundings of necrosis. The majority of these lymphocytes could be shown to be B cells, which morphologically included Reed-Sternberg (RS)-like cells, immunoblasts, medium-sized lymphoid cells, as well as cells with plasmacytoid differentiation. In all cases, a varying number of EBER-positive T cells could be identified. ISH for BHLF1-RNA detection showed that almost all cases contained single positive small lymphoid cells, indicating a transition from latent to productive infection cycle. Such cells could also be detected within the crypt epithelium reaching up to its surface. Additional screening of 123 oropharyngeal mucosa samples from patients without evidence of acute EBV-infection, using the polymerase chain reaction for EBV-DNA detection combined with EBER- and BHLF1-ISH showed single latently infected lymphocytes in only one case. Our data imply that infected lymphocytes and not epithelial cells are, in fact, the reservoir for EBV infection, and that these are the cells that participate in the interindividual virus transfer.

Adolescent↗

PubMed1995

Epstein-Barr virus in B-cell non-Hodgkin's lymphomas: unexpected infection patterns and different infection incidence in low- and high-grade types.

Two hundred and eight cases of B-cell non-Hodgkin's lymphoma (B-NHL) occurring in Europeans without any signs of HIV infection were investigated for their association with an Epstein-Barr virus (EBV) infection. The polymerase chain reaction (PCR) was applied for EBV-DNA detection, in situ hybridization (ISH) for the cellular localization of EBV-encoded small nuclear RNAs (EBER) and immediate-early RNAs (BHLF), and immunohistology (IH) for the detection of EBV-encoded latent membrane protein (LMP) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER-ISH produced congruent results in those cases with amplifiable DNA. EBV was present overall in 26 per cent (54/208) of the B-NHL cases. Through EBER-ISH, the virus could be localized merely in rare non-neoplastic bystander lymphocytes in 27 and additionally in tumour cells of 27 cases. Unexpectedly, the proportion of EBV-infected tumour cells present in the different cases varied between 1 and 100 per cent. All but three of the cases with infected tumour cells were of high-grade malignancy. Correlation with the morphological and immunological tumour phenotype revealed that all cases with more than 80 per cent EBER-positive tumour cells were either B-anaplastic large cell lymphomas (B-ALCL), sporadic Burkitt's lymphomas, or B-NHLs with partial or full plasmacellular differentiation. LMP was consistently absent from Burkitt's lymphomas and constantly expressed in B-ALCLs with EBER-positive tumour cells, while in all other instances it varied greatly and was rarer than EBER expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Viral↗

PubMed1995

[Primary brain lymphoma in acquired immunodeficiency syndrome. Immunophenotype and molecular pathologic characterization in stereotactic biopsy, autopsy and cerebrospinal fluid cytology].

In this study we present morphological, cytological, immunophenotypical, and molecular genetic features of ten cases of AIDS-related primary brain lymphomas obtained as sterotactic biopsies, autopsy specimens, or cerebrospinal fluid samples. Histologically, a very characteristic perivascular and diffuse lymphomatous spread in the brain parenchyma was observed. By applying a highly sensitive in situ hybridization technique (ISH) using digoxigenin-labeled antisense riboprobes, abundant Epstein-Barr virus (EBV)-encoded small nuclear RNAs (EBER) transcripts could be demonstrated in each case studied. A combination of ISH with immunohistochemical staining for latent membrane protein (LMP-1) and EBV nuclear antigen-2 (EBNA-2) showed different patterns of EBV latency with a predominance of the broad spectrum (EBER+/EBNA-2+/LMP-1+). Clonal rearrangements of immunoglobulin heavy chain (IgH) genes were demonstrated in four cases using a sensitive polymerase chain reaction. In one patient the rearrangement pattern suggested biclonal lymphoproliferation. Our observations confirm the implication of the EBV in the etiology of AIDS-related primary malignant lymphomas of the brain. The demonstration of EBV gene products and clonal IgH rearrangements even in small biopsy samples is a useful tool for distinguishing between reactive and neoplastic lymphocytic infiltrates, which are frequently observed in brain and cerebrospinal fluid specimens obtained from AIDS patients.

Adult↗

PubMed1995

Frequent presence of latent Epstein-Barr virus infection in peripheral T cell lymphomas. A review.

Two-hundred and four cases of peripheral T cell lymphoma (PTCL) occurring in Europeans without any sign of HIV-infection were investigated for their association with an Epstein-Barr virus (EBV) infection. Polymerase chain reaction (PCR) was applied for EBV-DNA detection, in situ hybridisation (ISH) for the cellular localization of EBV-encoded small nuclear RNA (EBER) and immediate early gene expression (BHLF) and immunohistology (IH) for the detection of EBV-encoded latent membrane protein 1 (LMP1) and EBV nuclear antigen 2 (EBNA2) expression. PCR and EBER-ISH produced congruent results in almost all cases with amplifiable DNA, leading to the finding of an overall frequency of EBV presence in 87/204 (42.6%) of the PTCL cases. Through EBER-ISH, the virus was identified to be exclusively present in small and blastic bystander lymphocytes in 29 cases, whilst an additional infection of neoplastic T cells was observed in the remaining 58 EBV-positive cases. The entity presenting with the most frequent EBV infection of tumour cells was that of angioimmunoblastic type PTCL, whilst the primary cutaneous PTCLs only seldom harbored the virus. Forty-eight of the EBV-positive TCLs showed an infection of a small proportion (1-20%) of the tumour cell population, whilst another ten cases, belonging to the pleomorphic TCL (PMTCL) group, displayed an infection of several to almost all neoplastic T cells (20-100%). Additional lytic EBV-infected cells could be detected in four cases by BHLF-ISH. LMP1 expression was present in a small proportion of the neoplastic T cells in 24 of the 58 cases with tumour cell infection, whilst an EBNA2 expression was detectable only in one case. Some non-malignant EBV-infected B-immunoblasts and Hodgkin/Reed Sternberg-like cells also expressed LMP1 in several cases. Our data imply a role of EBV in the pathogenesis of only a few PMTCL cases with predominant tumour cell infection, whilst the pathogenic significance of an EBV infection in the other PTCLs remains unclear due to the usually partial infection of the neoplastic cell component.

Antibodies, Monoclonal↗

PubMed1995

Change in the epidemiology of Reiter's syndrome (reactive arthritis) in the post-AIDS era? An analysis of cases appearing in the Greek Army.

OBJECTIVE: During the last 5 years we observed a significant decrease in the incidence of newly established cases of Reiter's syndrome (reactive arthritis) in Greek Army personnel. Our study was initiated to validate this observation and to evaluate a possible change in the prevalence of Reiter's syndrome (RS) associated infections. METHODS: The case records of patients with reactive arthritis (ReA) admitted during the periods 1980-83 and 1989-92 at a large Army Hospital were studied retrospectively and the cases of RS were reviewed. In addition, the prevalence of cases with urethritis and dysentery that presented to the hospital in the same periods was studied in retrospect, as these infections are known to participate in the etiopathogenesis of RS. RESULTS: A significant decrease in the overall incidence of the randomly presented RS cases during the second 4 year period was detected (27 versus 4 cases, p < 0.0001, chi 2 test). A similar significant decrease in the number of cases with gonococcal and nongonococcal urethritis was observed while the prevalence of dysentery was not significantly altered during the defined intervals. CONCLUSION: We suggest that the anti-AIDS campaign which began after the years 1984-85 is the principal cause of the observed change of epidemiology of RS cases appearing in the Greek Army.

Adult↗

PubMed1994

Frequent presence of latent Epstein-Barr virus infection in lymphoepithelioid cell lymphoma (Lennert's lymphoma).

This study deals with the investigation of the biological significance of an Epstein-Barr virus (EBV) infection in lymphoepithelioid cell lymphoma. A selection of EBV-detection techniques was applied to 15 cases, including polymerase chain reaction (PCR) for the detection of EBV-DNA, in situ hybridization (ISH) for the cellular localization of EBV-encoded small nuclear (EBER 1 and EBER 2) and immediate-early (BHLF) RNAs, and immunohistology for the detection of EBV-encoded latent membrane protein (LMP) expression. PCR and EBER-ISH produced congruent results in those cases with amplifiable DNA, leading to an EBV presence in 11/15 lymphoepithelioid cell lymphoma cases (73%). EBER-ISH combined with immunohistology localized the virus predominantly in several B immunoblasts and small B lymphocytes in eight of the EBV-positive cases, five of which also contained single infected lymphocytes expressing T-cell characteristic antigens. LMP was detected using immunohistology in only a proportion of immunoblasts in four of these cases. The remaining three EBV-positive lymphoepithelioid cell lymphoma cases contained only single EBER-positive small B lymphocytes without LMP expression. No case contained BHLF-RNA expressing cells. These data imply that, although latently EBV-infected cells are frequently present in lymphoepithelioid cell lymphoma cases, the virus is probably not directly involved in the pathogenesis of this entity.

Antibodies, Monoclonal↗

PubMed1993

Frequent latent Epstein-Barr virus infection of neoplastic T cells and bystander B cells in human immunodeficiency virus-negative European peripheral pleomorphic T-cell lymphomas.

We investigated 81 cases of peripheral pleomorphic T-cell lymphoma (PMTCL) occurring in human immunodeficiency virus-negative Europeans for the presence of Epstein-Barr virus (EBV)-DNA through polymerase chain reaction (PCR) for the presence of EBV-encoded small nuclear RNAs (EBER) and immediate early mRNAs (Bam H-fragment, lower strand frame [BHLF]) by in situ hybridization (ISH) and for EBV-encoded latent membrane protein (LMP) and nuclear antigen 2 (EBNA2) by immunohistology (IH). EBER-ISH, which could be applied on all cases, showed an overall incidence of EBV-infected cells in 38 of 81 cases (47%) of PMTCL. These data could be confirmed by PCR, which produced congruent results in the cases with amplifiable DNA. By EBER-ISH, the virus was located in the tumor cells in 30 of the 38 EBV-positive cases, with the proportion of the infected cells ranging from 1% to 100%. In 18 of these cases and in the 8 cases without EBV-infected tumor cells, the virus was, respectively, either additionally or exclusively detectable in occasional nonmalignant lymphoid bystander cells. An LMP expression was observed in several of the EBER-expressing tumor cells in 18 cases, whereas EBNA2 was detectable only in one case, which also displayed signs of viral replication. Some nonmalignant EBV-infected B immunoblasts also expressed LMP in several cases. Primary cutaneous and enteropathy-associated PMTCL displayed less frequent EBV infection when compared with other extranodal or nodal manifestations.

Adult↗