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I Anagnostopoulos

Publications and source records attributed to I Anagnostopoulos.

At least 55 records · Page 3Linked to original sources
PubMed1999

Common and HIV-related diffuse large B-cell lymphomas differ in their immunoglobulin gene mutation pattern.

HIV-infected patients are at high risk of developing diffuse large B-cell lymphomas (DLBCL). It is currently unclear whether these lymphomas represent Epstein-Barr virus (EBV)-driven lymphoproliferations that develop in the setting of immunodeficiency, or whether these tumours are more closely related to the DLBCL seen in the general population. To clarify this issue, 12 HIV-related DLBCL from 11 patients were analysed for the presence of clonally rearranged and somatically mutated immunoglobulin heavy chain (IgH) genes and their association with EBV was determined. Eleven of the 12 tumour samples displayed monoclonal rearrangements of the IgH genes, with or without a moderate number of somatic mutations in the CDRII and in the FWIII regions (average four mutations). One patient presented two successive lesions; whereas the initial tumour showed an oligoclonal IgH rearrangement, the lymphoma at relapse proved to harbour a monoclonal B-cell population. Ten of 12 tumour samples expressed the EBV encoded small RNAs (EBERs), and six of these EBV-positive cases displayed, in addition, an expression of the EBV encoded nuclear antigen 2 (EBNA-2). The results obtained from HIV-related DLBCL are at variance to those described for DLBCL occurring in the general population, since the latter contain significantly more somatic IgH mutations in the CDRII and in the FWIII regions and are only rarely associated with EBV. It is concluded from these findings that HIV-related DLBCL represent a distinct group of B-cell lymphomas, a significant fraction of which most likely originates from EBV-driven lymphoproliferations, and that half of the cases derive from pre-germinal centre B-cells.

Gene Rearrangement↗
PubMed1999

T-cell and T/natural killer-cell lymphomas involving ocular and ocular adnexal tissues: a clinicopathologic, immunohistochemical, and molecular study of seven cases.

OBJECTIVE: Lymphomas of the eye and its adnexa are frequently of B lineage. This study aims to characterize the clinical and histopathologic features of the rare non-B-cell non-Hodgkin lymphomas (NHL) of these locations. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Seven cases of T- and T/NK-cell lymphomas involving the ocular and ocular adnexal tissues. METHODS: A morphologic, immunohistochemical, and molecular analysis (polymerase chain reaction) of each of the tumors was undertaken. The lesions were classified according to the Revised European-American Lymphoma (REAL) classification. The clinical and follow-up data were collected. RESULTS: The patients included four women and three men ranging in age from 32 to 88 years (mean, 63 years). The presenting ophthalmic symptoms varied from a small nodule on the upper eyelid and conjunctival swellings to dramatic loss of vision associated with gross protrusion of the globe. Five of the cases presented were secondary manifestations of a systemic lymphoma in ocular tissues; two cases represented primary disease. Three cases were "peripheral T-cell lymphomas (PTCL), unspecified" with positivity for CD3, CD8, and betaF1 and negativity for CD56. Two cases were CD3+, CD30+, and CD56- and were classified as "anaplastic large-cell lymphomas of T-cell type" (T-ALCL). The remaining two cases showed an immunophenotype of CD3+, CD56+, and betaF1- and proved to contain Epstein-Barr virus (EBV) by in situ hybridization, consistent with "T/natural killer (NK)-cell lymphoma of nasal type." Clonal T-cell populations were shown in all three of the PTCLs by Southern blot (n = 1) and polymerase chain reaction (n = 2) for the T-cell receptor gamma and beta genes in one case of ALCL but not in the T/NK-cell lymphomas. Five patients died within 2 years; only two patients (one primary PTCL and one cutaneous T-ALCL) were disease free at 4 and 5 years' follow-up, respectively. CONCLUSION: This study shows that a heterogeneous group of T-cell lymphomas can involve the eye and its adnexal tissue. Most T-cell neoplasms are secondary manifestations of systemic disease and carry a poor prognosis. These findings, in conjunction with published data on ocular B-NHL, also indicate that immunophenotypic differentiation between T- and B-NHL in these locations is of clinical importance.

Adult↗
PubMed1999

Molecular characterisation of the defective alpha 1-antitrypsin alleles PI Mwurzburg (Pro369Ser), Mheerlen (Pro369Leu), and Q0lisbon (Thr68Ile).

Deficiency of the serine proteinase inhibitor (serpin) alpha 1-antitrypsin (alpha 1AT) is the most common autosomal recessive genetic disorder in Northern Europe. alpha 1AT is the physiological regulator of the proteolytic enzyme neutrophil elastase and severe deficiency states are associated with an increased risk of developing chronic obstructive pulmonary disease (COPD) as a consequence of chronic proteolytic damage to the lungs. Among the known mutations of the alpha 1AT gene causing severe alpha 1AT deficiency and COPD a few alleles are also associated with liver disease. When expressed in cell cultures, all these particular alleles cause intracellular alpha 1AT accumulation which appears to be a prerequisite for the development of hepatic injury. Liver disease is seen in only a small fraction of all patients carrying such alleles, however. The reason for this is not completely clear, but there is evidence that PI ZZ individuals 'susceptible' to liver disease carry an additional defect affecting protein degradation in the endoplasmic reticulum (ER). We characterise a newly identified defective alpha 1AT allele PI Mwürzburg (Pro369 [CCC] to Ser [TCC]) associated with a complete intracellular transport block in cell cultures in vitro. The allele PI Mheerlen, a previously described different amino acid substitution in the same position as PI Mwürzburg (Pro369 [CCC] to Leu [CTC]) is shown to cause complete retention of the mutant alpha 1AT in the ER, too, whereas in the recently described mutant allele PI Q0lisbon (Thr68 [ACC] to Ile [ATC]) a significantly reduced alpha 1AT secretion from the cells was observed. Adenovirus-mediated recombinant expression of mutant Mwürzburg and Mheerlen, and of wild-type alpha 1AT in mouse liver in vivo showed that the mutant human proteins were not secreted into the mouse plasma, in contrast with human wild-type alpha 1AT which circulated at high concentrations over several weeks. In summary, all transportation deficient alpha 1ATs analysed have the potential to cause lung disease in the homozygous state or in heterozygous carriers of another deficiency allele, and they may also cause liver disease in certain patients. The mutant PI Mwürzburg and Mheerlen alpha 1ATs are completely retained within synthesising cells, and the molecular defect of transportation in these two alleles may be similar to that in the common PI Z allele. The molecular defect in the PI Q0lisbon allele (Thr68Ile) shows similarity with the immediately neighbouring Mmineral springs mutation (Gly67Glu).

Adult↗
PubMed1999

Origin of primary gastric T-cell lymphomas from intraepithelial T-lymphocytes: report of two cases.

AIMS: The classification of primary gastric T-cell lymphomas is uncertain due to the exceeding rarity of these tumours; many of the reported cases were felt to be similar to node-based lymphomas. We describe two cases of primary gastric T-cell lymphoma with evidence of origination from intraepithelial T-lymphocytes. METHODS AND RESULTS: Both tumours were restricted to the stomach; one displaying a large ulcerated mass, the other a widespread superficial tumour manifestation. Histologically the first tumour was composed of sheets of medium-sized lymphoid cells showing marked epitheliotropism at the edge of the ulcer, and a CD3+, CD4-, CD8-, CD20-, CD56-, CD103+, beta F1+ phenotype. The second case differed histologically and immunophenotypically from the first case. In addition to lamina propria and submucosal infiltration, the lymphoma contained an extensive intraepithelial component even in large areas without other evidence of tumour. The neoplastic cells ranged in size from small to medium and large. Immunohistology disclosed a CD3+, CD4+, CD8-, CD20-, CD56-, beta F1+ phenotype. Staining for CD103 could not be performed in this case since frozen material was not available. CONCLUSIONS: The prominent epitheliotropism, the marked intraepithelial growth and the expression of CD103 strongly imply a derivation of these primary gastric lymphomas from intraepithelial T-lymphocytes. Additional studies of larger series will clarify whether the findings described here are typical of primary gastric T-cell lymphomas.

Adult↗
PubMed1999

Tenascin labelling in colorectal biopsies: a useful marker in the diagnosis of collagenous colitis.

AIMS: This study was undertaken to clarify whether immunohistological detection of tenascin (TN), an extracellular matrix glycoprotein that is expressed during stromal remodelling, may allow a more precise diagnosis of collagenous colitis. METHODS AND RESULTS: We studied multiple colorectal biopsies specimens from 15 patients with clinically suspected collagenous colitis for TN expression by using a monoclonal antibody. Biopsies from further 15 patients without symptoms and signs of collagenous colitis served as controls. In seven of the 15 cases with clinically suspected collagenous colitis a prominent and selective subepithelial tenascin expression was identified. The TN expression pattern closely correlated with the conventional detection of a subepithelial collagen band diagnostic of collagenous colitis. The immunohistological labelling for TN allowed a quicker and more precise measurement of the thickness of the diagnostic collagen deposits than conventional staining. By this approach one further case could be reclassified as collagenous colitis. CONCLUSIONS: Our data show that immunohistological detection of TN allows a more correct and easy diagnosis of collagenous colitis.

Adult↗
PubMed1999

Classical Hodgkin's disease and follicular lymphoma originating from the same germinal center B cell.

PURPOSE: Classical Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. To clarify whether these different diseases share a common precursor cell, we analyzed the immunoglobulin rearrangements in tumor cells of the classical Hodgkin's disease and the follicular lymphoma that developed in the same patient 2 years apart. PATIENTS AND METHODS: Polymerase chain reaction (PCR) for the detection of rearranged immunoglobulin genes was carried out on single Reed-Sternberg cells and on whole tissue DNA extracted from the follicular lymphoma. PCR products were sequenced and compared with each other and with germ line immunoglobulin variable segments. Immunoglobulin heavy- and light-chain transcripts were analyzed by radioactive in-situ hybridization. RESULTS: The same monoclonal immunoglobulin gene rearrangement was found in both neoplasms. The variable region of the immunoglobulin heavy-chain genes of the Reed-Sternberg and of the follicular lymphoma cells were differently mutated, but six somatic mutations were shared by both lymphoma cells. Although the coding capacity of the immunoglobulin genes was preserved in both neoplastic cell populations, immunoglobulin heavy- (mu) and light- (kappa) chain expression was restricted to the follicular lymphoma cells, except for small amounts of kappa light-chain mRNA in some Reed-Sternberg cells. CONCLUSIONS: The neoplastic cells of the Hodgkin's disease and the follicular lymphoma that occurred in this patient derived from a common precursor B cell. Its differentiation stage could be identified as that of a germinal center B cell. Thus, transforming events can be more important than the cell of origin in determining a disease entity.

Adult↗
PubMed1999

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗
PubMed1999

Immunoglobulin VH gene expression among extranodal marginal zone B-cell lymphomas of the ocular adnexa.

PURPOSE: Most lymphomas of the ocular adnexa are primary extranodal non-Hodgkin's lymphomas of the B-cell type, with the most common lymphoma subtype being the extranodal marginal-zone B-cell lymphoma (EMZL). Analysis of somatic mutations in the variable (V) region of the Ig heavy (H)-chain gene segment suggests that EMZL development in other locations is dependent on antigen stimulation. The purpose of this study was to analyze the presence of somatic hypermutations in clonally rearranged Ig H-chain V genes of this lymphoma entity in the ocular adnexa and to estimate whether the mutation pattern is compatible with antigen selection. METHODS: Twenty-six cases of EMZL of the ocular adnexa were diagnosed on the basis of morphology, histology, and immunohistology. A nested polymerase chain reaction (PCR) was performed on DNA extracted from paraffin sections. The isolated PCR products were sequenced and compared with published VH germline segments to determine the number of somatic mutations in the complementarity-determining region (CDR) 2 and framework (FW) region 3. RESULTS: The number of somatic mutations in the cases of EMZL varied between 0 and 24: Five cases involved 0 to 3 somatic mutations, and the remaining 21 cases involved 4 to 24 mutations. Based on the ratio of replacement (R) to silent (S) mutations in the CDR2 or FW3 regions, antigen selection seems to have occurred in 60% of ocular adnexal EMZL. The VH3 family was the most commonly expressed germline VH family (54%), followed by VH4 (23%), with biased usage of the latter. Some germline VH1 genes used included DP-8, DP-10, DP-53, DP-63 (VH4.21), and DP-49, which are frequently used by autoantibodies (e.g., rheumatoid factors) and natural autoantibodies. CONCLUSIONS: EMZLs of the ocular adnexa have an Ig H-chain mutation pattern that supports the concept that they represent a clonal expansion of post-germinal-center memory B-cells in most instances. In two thirds of cases, antigen selection may have occurred, and autoantibodies may have a role in their development.

Adolescent↗
PubMed1998

CD40 ligand on activated platelets triggers an inflammatory reaction of endothelial cells.

CD40 ligand (CD40L, CD154), a transmembrane protein structurally related to the cytokine TNF-alpha, was originally identified on stimulated CD4+ T cells, and later on stimulated mast cells and basophils. Interaction of CD40L on T cells with CD40 on B cells is of paramount importance for the development and function of the humoral immune system. CD40 is not only constitutively present on B cells, but it is also found on monocytes, macrophages and endothelial cells, suggesting that CD40L has a broader function in vivo. We now report that platelets express CD40L within seconds of activation in vitro and in the process of thrombus formation in vivo. Like TNF-alpha and interleukin-1, CD40L on platelets induces endothelial cells to secrete chemokines and to express adhesion molecules, thereby generating signals for the recruitment and extravasation of leukocytes at the site of injury. Our results indicate that platelets are not only involved in haemostasis but that they also directly initiate an inflammatory response of the vessel wall.

Blood Platelets↗
PubMed1998

Lymphoproliferative lesions of the ocular adnexa. Analysis of 112 cases.

OBJECTIVE: Lymphoproliferative lesions of the ocular adnexa were analyzed to examine (1) the suitability of the Revised European-American Lymphoma (REAL) classification for the subtyping of the lymphomas in these sites; (2) the predictive value of the REAL classification for the evolution of these tumors; and (3) the frequency and prognostic impact of tumor type, location, proliferation rate (Ki-67 index), p53, CD5 positivity and the presence of monoclonality within these tumors. DESIGN: Retrospective review. METHODS: The clinical, histomorphologic, immunohistochemical, and molecular biologic (polymerase chain reaction [PCR]) features of lymphoid proliferations of the ocular adnexa were studied. STUDY MATERIALS: The ocular adnexal lymphoproliferative lesions were located as follows: orbit in 52 patients (46%), conjunctiva in 32 patients (29%), eyelid in 23 patients (21%), and caruncle in 5 patients (4%). RESULTS: Reactive lymphoid hyperplasia was diagnosed in 12 cases and lymphoma in 99 cases; 1 case remained indeterminate. The five main subtypes of lymphoma according to the REAL classification were extranodal marginal-zone B-cell lymphoma (64%), follicle center lymphoma (10%), diffuse large cell B-cell lymphoma (9%), plasmacytoma (6%), and lymphoplasmocytic lymphoma (5%). Age, gender, and anatomic localization of the lymphomas did not have prognostic significance during a follow-up period of 6 months to 16.5 years (mean, 3.3 years). Extent of disease at time of presentation was the most important clinical prognostic factor: advanced disease correlated with increased risk ratios of having persistent disease at the final follow-up and with lymphoma-related death (P < 0.001). Histomorphologic features and immunohistochemical markers positively correlating with disseminated disease at presentation, stage at final follow-up, and occurrence of lymphoma-related death included cytologic atypia (P < 0.001), MIB-1 proliferation rate (P < 0.001), and tumor cell p53 positivity (P < 0.001). The MIB-1 proliferation rates greater than 20% in extranodal marginal-zone B-cell lymphoma corresponded to at least stage II lymphoma (P < 0.05). CONCLUSION: The REAL classification is suitable for the subdivision of the ocular adnexal lymphomas. The MIB-1 proliferation rate and p53 positivity may aid the prediction of disease stage and disease progression, whereas PCR can support the diagnosis and reduce the number of histologically indeterminate lesions.

Adolescent↗
PubMed1998

Improved polymerase chain reaction detection of clonally rearranged T-cell receptor beta chain genes.

A new method for the detection of all known possible rearrangements at the variable (V), diversity (D), and joining (J) segments of the T-cell receptor beta chain (TcR beta) gene in tissue DNA extracts is described that involves two polymerase chain reactions (PCRs). The first PCR round (screening PCR) allowed the identification of the J beta segment involved in a clonal rearrangement. A J beta-primer was used for the second PCR (J beta-specific PCR), recognizing the J beta segment identified in the screening PCR in combination with a consensus V beta primer. This PCR generated prominent and short amplificates suitable for direct sequence analysis because of their low background. Using this approach, clonal TcR beta gene rearrangements were able to be demonstrated in all T-cell lines (n = 7) and in all peripheral T-cell lymphomas (n = 33) analyzed. No clonal TcR beta gene rearrangements were found in any of the normal tissues studied nor in any B-cell non-Hodgkin lymphomas. This method is applicable to DNA from fresh frozen tissues, and, after the TcR beta rearrangement of a patient's malignant T-cell clone has been identified by the screening PCR, DNA can also be detected in follow-up formalin-fixed paraffin-embedded samples by the J beta-specific PCR with high sensitivity and specificity.

Clone Cells↗
PubMed1998

Expression patterns of cyclin D1 and related proteins regulating G1-S phase transition in uveal melanoma and retinoblastoma.

BACKGROUND/AIMS: A checkpoint mechanism in late G1, whose regulation via loss of retinoblastoma protein (pRB) or p16, or overexpression of cyclin D1 or cyclin dependent kinase 4 (CDK4), has been proposed to constitute a common pathway to malignancy. The aims of this study were (a) to compare markers of cell cycle G1-S phase transition in an intraocular tumour with known pRB deficiency (retinoblastoma) and compare it with one with an apparently functional pRB (uveal melanoma); (b) to determine if one of these markers may have a role in the pathogenesis of uveal melanoma; and (c) to determine if there is a difference in cell cycle marker expression following treatment of uveal melanoma and retinoblastoma. METHODS: 90 eyes were enucleated from 89 patients for retinoblastoma (n = 24) or for choroidal or ciliary body melanoma (n = 66). Conventional paraffin sections were assessed for cell type and degree of differentiation. Additional slides were investigated applying standard immunohistochemical methods with antibodies specific for cyclin D1 protein, pRB, p53, p21, p16, BCL-2, and MIB-1. RESULTS: Cyclin D1 protein and pRB were negative in retinoblastoma using the applied antibodies. In contrast, cyclin D1 protein expression was observed in 65% of uveal melanomas; a positive correlation between cyclin D1 cell positivity and tumour cell type, location, growth fraction, as well as with pRB positivity was observed. p53, p21, and p16 could be demonstrated in both tumours. An inverse relation between p53 and p21 expression was demonstrated in most choroidal melanomas and in some retinoblastomas. Apart from a decrease in the growth fractions of the tumours as determined by MIB-1, a significant difference in the expression of G1-S phase transition markers in vital areas of uveal melanoma and retinoblastoma following treatment with radiotherapy and/or chemotherapy was not observed. CONCLUSION: Retinoblastomas and uveal melanomas, two tumours of differing pRB status, differ also in their immunohistochemical pattern for markers of the G1-S phase transition of the cell cycle. The results of the present study support the concept of (a) an autoregulatory loop between pRB and cyclin D1 in tumours with a functional pRB and the disruption of this loop in the presence of pRB mutation, as well as (b) a checkpoint mechanism in late G1, whose regulation via loss of p16 or pRB, or overexpression of cyclin D1 constitutes a common pathway to malignancy. Further, the results raise the possibility of cyclin D1 overexpression having a role in the pathogenesis of uveal melanoma.

Adolescent↗
PubMed1997

Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells.

BACKGROUND: The atypical cells of nodular lymphocyte-predominant Hodgkin's disease, designated lymphocytic and histiocytic (L&H) cells, have a B-cell phenotype. To clarify the clonality of these cells, we studied rearranged immunoglobulin genes for the variable region of the heavy chain (V[H] genes) in individual L&H cells from 11 patients with nodular lymphocyte-predominant Hodgkin's disease. We also studied the expression of immunoglobulin light chains by those cells in six of the same patients. METHODS: Single CD20+ L&H cells were isolated from frozen sections by a technique of micromanipulation. The rearranged V(H) genes of these cells were amplified by the polymerase chain reaction (PCR), sequenced, and compared with germ-line V(H) genes. Immunoglobulin light-chain messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Of 615 L&H cells isolated from all the frozen sections, 160 yielded PCR products. In each of the 11 patients, the L&H cells that could be evaluated had identically rearranged V(H) genes, whether they were isolated from the same nodule, different nodules, or different blocks of tissue. All the V(H) sequences derived from the L&H cells were highly mutated (7.5 to 27.2 percent). In two cases the coding capacity of the V(H) genes was completely or partially disrupted by mutations. Intraclonal diversity was found in six cases, and monotypic immunoglobulin light-chain mRNA was found in six. CONCLUSIONS: The L&H cells of nodular lymphocyte-predominant Hodgkin's disease represent a monoclonal expansion of B cells. The high load of V(H) gene mutations and signs of intraclonal diversity suggest a relation between L&H cells and germinal-center B cells at the centroblastic stage of differentiation.

B-Lymphocytes↗
PubMed1997

Strict lymphotropism of Epstein-Barr virus during acute infectious mononucleosis in nonimmunocompromised individuals.

Previous investigations of exfoliated oropharyngeal cells from individuals suffering from infectious mononucleosis (IM) suggested that the oropharyngeal epithelia are the primary target and also the site of life-long persistence of the Epstein-Barr virus (EBV). This concept was widely accepted. However, the investigation of histological sections with more sensitive EBV detection techniques has drawn this concept into doubt since EBV proved to be constantly absent in normal epithelial cells. To elucidate the discrepancy, throat washings and peripheral mononuclear blood cells from 16 patients suffering from IM were investigated for EBV-DNA and EBV gene products employing highly sensitive in situ hybridization, immunocytochemistry, and polymerase chain reaction. Although all patients exhibited latently infected B lymphocytes in peripheral blood, samples of exfoliated oropharyngeal cells were constantly EBV-negative with the exception of three cases. In these cases, the patients additionally suffered from purulent ulcerating tonsillitis, EBV-infected B cells, but no EBV-infected epithelial cells were detectable. These findings support the view that recirculating lymphocytes of B-cell origin, but not epithelial cells are the initial target of EBV during primary infection and that B cells also represent the site of life-long viral persistence.

Adolescent↗
PubMed1997

Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection.

We report here a series of 16 highly malignant diffuse large B-cell lymphomas of the oral cavity with unique immunohistologic features. Fifteen of these developed in human immunodeficiency virus-positive patients. All cases displayed morphologic features of diffuse large-cell lymphomas but strikingly differed from them in that they showed a minimal or absent expression of the leukocyte common antigen as well as of the B-cell antigen CD20. Instead, the tumor cells showed a constant reaction with the plasma cell characteristic antibody VS38c and a frequent reaction with the CD79a antibody. This, in conjunction with a variable expression of cytoplasmic Ig and a monoclonal rearrangement of the Ig heavy chain gene in all of the three tested cases confirmed the B-cell nature, the clonal origin, and the plasmacellular differentiation of these neoplasms. The majority of these tumors were negative for the BCL-6 protein, with the remaining cases showing only a partial and weak expression of this antigen. An association with the Epstein-Barr virus (EBV) was found in 9 of 15 tested cases showing abundant EBV-encoded nuclear RNA transcripts in the absence of EBNA-2. Five of the EBV-positive cases variably expressed LMP-1. We propose to name these tumors plasmablastic lymphomas, in accordance with their morphologic and immunohistologic features. Knowledge of this lymphoma entity is important to avoid confusion with nonlymphoid malignancies due to the lack of commonly used lymphoid markers.

Adult↗
PubMed1997

Expression of cytotoxic molecules in intestinal T-cell lymphomas. The German Study Group on Intestinal Non-Hodgkin Lymphoma.

Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from alpha beta intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial alpha beta cytotoxic T-lymphocytes.

Adult↗
PubMed1997

Disappearance of the Epstein-Barr virus in a relapse of Hodgkin's disease.

Hodgkin's disease (HD) is associated with the Epstein-Barr virus (EBV) in approximately half of cases. This is a report of a case of nodular sclerosing HD of the B-cell type that was associated with EBV in the initial manifestation, but was found to be EBV-negative in the relapse of the tumour. Both tumours displayed similar clinical, pathological, and immunohistochemical features. This finding implies that in a given individual EBV can be lost from malignant tumours and therefore shows that the EBV infection is not required to maintain neoplastic growth of HD tumour cells.

Antigens, Viral↗