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T C Diss

Publications and source records attributed to T C Diss.

68 records · Page 4Linked to original sources

Detection of monoclonality in low-grade B-cell lymphomas using the polymerase chain reaction is dependent on primer selection and lymphoma type.

Detection of B-cell monoclonality using the polymerase chain reaction (PCR) promises the quick and cost-effective separation of monoclonal from polyclonal B-cell disease. However, the efficiency of the method has yet to be fully assessed, particularly with regard to disease type and selection of PCR primers. We have evaluated two approaches based on amplification of the immunoglobulin heavy chain gene using framework 2 (Fr2) and framework 3 (Fr3) region primers. Frozen tissue samples from 94 cases of low-grade B-cell lymphoma were investigated, all of which had previously been shown to be monoclonal by Southern blot analysis. Using a Fr2 primer, we were able to show monoclonality in 85 per cent of cases; with Fr3, 80 per cent of cases; and using both techniques in separate reactions, 90 per cent of cases. Thus, a significant false-negative rate exists with either primer which can be reduced by using both. We also found a difference in the efficiency of detection in different types of lymphoma; only 87 per cent of mucosa-associated lymphomas and centroblastic/centrocytic lymphomas were shown to be monoclonal, whereas all of the other lymphoma types tested were positive using one or both methods. We conclude that PCR detection of B-cell monoclonality allows rapid analysis of tissue samples, including paraffin-processed material. False-negative results which occur in some types of lymphoma can be reduced by the use of two or more primer combinations.

Base Sequence↗

Epstein-Barr virus (EBV) in enteropathy-associated T-cell lymphoma (EATL).

Using Southern hybridization analysis, we have detected the Epstein-Barr virus (EBV) genome in 36 per cent (4/11) of enteropathy-associated T-cell lymphoma (EATL), a frequency much higher than that seen in nodal T-cell lymphomas in which we were able to show EBV DNA in only 3 per cent (1/30) of the cases examined. Using a terminal fragment probe, monoclonal proliferation of EBV in infected cells was demonstrated in three of the four EBV-positive EATL cases (in one case, insufficient signal prevented the determination of EBV clonality). The EBV genome and an early transcript, EBER1, were identified in tumour cells by in situ hybridization. Expression of latent membrane protein (LMP) was detected in two EBV DNA/RNA-positive EATL cases. In view of the known oncogenic properties of EBV and the putative central role of LMP in EBV-induced cell immortalization, the results of this study suggest that the virus may play an aetiological role in the pathogenesis of EATL.

Blotting, Southern↗

Breast lymphomas: a clinicopathologic review.

Primary lymphoma is an uncommon tumor in the breast. Review of the literature shows two distinct clinicopathologic groups. One, which affects young women, is frequently bilateral, is often associated with pregnancy, and is a Burkitt-type lymphoma. The second group affects older women, is usually B-cell non-Hodgkins-type lymphoma, and presents clinical features identical to carcinoma of the breast. Three recent studies have suggested that up to half of the cases in the latter group belong to the category of lymphomas arising from the mucosa-associated lymphoid tissues. We have identified nine cases of primary lymphoma from the files of Guys Hospital Clinical Oncology Breast Unit in the 16-year period from 1974 to 1990. The clinical features have been reviewed and the tumors have been evaluated both on a morphologic and an immunohistochemical basis, and seven of nine of the cases have been screened for t[14;18] translocation using the polymerase chain reaction. All the tumors occurred in women older than 50 years and who presented with features of mammary carcinoma. One tumor was true histiocytic lymphoma; the remaining eight cases were B-cell lymphomas. Seven of the latter cases were high-grade B-cell lymphomas and one was a true follicular lymphoma. None of our cases showed the features of lymphoma arising in mucosa-associated lymphoid tissue.

Aged↗

Primary low-grade B-cell lymphoma of the conjunctiva: a mucosa-associated lymphoid tissue type lymphoma.

We describe the clinical presentation, morphology, immunophenotypic features and molecular biology of seven cases of conjunctival lymphoid infiltration. In five cases there was either immunophenotypic or molecular evidence of B-cell lymphoma. Each of these cases showed the morphological, immunophenotypic and molecular feature of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. The findings suggest that most conjunctival lymphomas are of this type and explains their uniformly favourable prognosis.

Adult↗

Cytogenetic study of B-cell lymphoma of mucosa-associated lymphoid tissue.

The recently described B-cell lymphomas arising in mucosa-associated lymphoid tissue (MALT) form a distinct clinico-pathologic group of non-Hodgkin's lymphoma, and therefore would be expected to be characterized by a recurrent chromosomal aberration. We have analyzed the cytogenetics of 23 cases of MALT lymphomas arising in the stomach, small intestine, lung, and lacrimal gland. In each case the presence of an abnormal clonal cell population was confirmed by the identification of rearranged bands when digested tumor DNA was hybridized with a probe to the joining region of the immunoglobulin heavy chain gene. Metaphase spreads were obtained in 14 cases, of which 9 cases showed an abnormal karyotype. Although no unifying aberration was detected, rearrangements of chromosome 1p, and numerical abnormalities of chromosomes 3 and 7, may play a role in the genesis of these tumors.

Chromosome Aberrations↗

Follicular colonization in thyroid lymphoma.

The presence of neoplastic (light chain restricted) B-cell follicles in low-grade B-cell gastrointestinal (GI) lymphoma of mucosa-associated lymphoid tissue (MALT) has been explained on the basis of specific colonization of reactive follicles by centrocyte-like (CCL) cells. Low-grade B-cell thyroid lymphomas have been included in the category of MALT lymphoma, but the frequent presence of a follicular pattern in these tumors has contributed to the view that they are follicle center cell (FCC) tumors. We have reviewed the histology and investigated the phenotype and genotype of nine cases of primary low-grade B-cell lymphoma of the thyroid, all of which were distinguished by a predominantly follicular pattern. All cases also demonstrated features of MALT lymphoma, including CCL cells and lymphoepithelial lesions. The appearances and immunohistology of the follicles were those of follicular colonization as described in GI MALT lymphoma rather than FCC follicular lymphoma. The predominant pattern of follicular colonization was replacement of the follicle center by slightly enlarged CCL cells that showed a strikingly high proliferation rate. No evidence of the t(14;18) translocation was found in any case, using the polymerase chain reaction (PCR) on DNA extracted from fresh (n = 1) or paraffin-embedded (n = 9) tissue. These findings argue against a FCC lineage for primary thyroid lymphomas and support their inclusion in the MALT category.

Base Sequence↗

A study of the properties of a low-grade mucosal B-cell lymphoma using a monoclonal antibody specific for the tumour immunoglobulin.

Primary low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are tumours with distinctive clinico-pathological characteristics, two of which are studied in this paper, namely the tendency of the tumours to remain localized and the morphologic and phenotypic resemblance of the malignant cells to splenic marginal zone B cells. We have made a detailed study of a small intestinal lymphoma and a gastric lymphoma, which together with the spleen were resected from the same patient. Using a monoclonal antibody (7G3) raised against a unique determinant on the small intestinal tumour, we were able to detect disseminated small intestinal tumour cells in the stomach and spleen. The tumour in the stomach was genetically related, but non-identical to that in the small intestine, and was not recognized by 7G3. Lymphocytes expressing the marker of the small intestinal tumour (7G3) were present in lymphoid nodules in the stomach, and 7G3+ plasma cells were present beneath the gastric epithelium. In the spleen, cells expressing 7G3 were present in the marginal zone and plasma cells expressing the same marker were present in the red pulp. These findings suggest that low-grade MALT lymphomas may migrate beyond the primary tumour site, but that tumour cells distant to the primary site may differentiate into mature, non-dividing plasma cells. The localization of small intestinal tumour cells in the splenic marginal zones reinforces the suggestion of lineage homology between these populations of cells.

Antibodies, Monoclonal↗

A genotypic study of low grade B-cell lymphomas, including lymphomas of mucosa associated lymphoid tissue (MALT).

Genotypic analysis has led to the implication of certain oncogenes in the pathogenesis of specific groups of non-Hodgkin's lymphoma. Rearrangements of c-myc are associated with Burkitt's lymphoma and of bcl-2 with centroblastic/centrocytic lymphoma. Rearrangement of bcl-1 has yet to be associated with a specific group of lymphoma. In this study DNA from 62 cases of low grade B-cell lymphoma, classified using the Kiel classification, were analysed by Southern blotting and hybridization with probes to bcl-1, bcl-2, and c-myc. Rearrangements of bcl-2 were found in a proportion of centroblastic/centrocytic lymphoma comparable to other published studies. Rearrangement of c-myc was not found in any case studied. Bcl-1 rearrangement was found in 2/9 cases of B-CLL, and 3/6 cases of centrocytic lymphoma. This incidence of bcl-1 rearrangement in centrocytic lymphoma suggests that it is a characteristic change. No rearrangement of bcl-1, bcl-2 or c-myc was found in any case of lymphoma of mucosa associated lymphoid tissue (MALT), providing further evidence that, in spite of having a similar morphology to some other groups of low grade B-cell lymphoma, lymphomas of MALT comprise a distinct entity.

Blotting, Southern↗

Low-grade primary B-cell lymphoma of the lung. An immunohistochemical, molecular, and cytogenetic study of a single case.

A case of primary low-grade pulmonary lymphoma is described. The histologic features conformed to those laid down by Saltzstein for a diagnosis of "pseudolymphoma." However, the immunocytochemical and molecular investigations confirmed the tumor to be a low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT). Cytogenetic studies revealed an abnormal karyotype with a translocation t(1;14). This is the first reported case of an abnormal karyotype in a case of a lymphoma of MALT.

Antigens, Differentiation↗

Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer in human intestinal intraepithelial lymphocytes.

Immunohistochemistry has been used to investigate disulfide- and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer (TcR gamma/delta) in blood and intestinal epithelium of normal human small intestine, intestine of patients with untreated coeliac disease (in whom T cells expressing TcR gamma/delta are disproportionately raised), intestine of patients with tropical malabsorption, and in the human fetus. In blood from adult volunteers, 90% of T cells expressing TcR gamma/delta use the disulfide-linked form. In contrast in the epithelium in normal small intestine, coeliac disease and tropical malabsorption, most of the T cells expressing TcR gamma/delta use the non-disulfide-linked form. This is especially prominent in untreated coeliac disease where the increase in TcR gamma/delta T cells is mainly restricted to those using the non-disulfide-linked form. In human fetal small intestinal epithelium, however, only cells using the disulfide-linked form are present. These variations in expression of different forms of TcR gamma/delta in the gut epithelium in different conditions suggests that antigen, or some as yet undefined factor may determine the frequency of each subpopulation.

Antibodies, Monoclonal↗

Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine).

Studies of the morphologic and phenotypic diversity of intraepithelial T cells in human small intestine have shown them to be heterogeneous, yet distinct from most extra intestinal T cells. In this study sequential immunoenzymatic staining was used to define new intraepithelial lymphocyte subpopulations in man. In normal human jejunum approximately 6% of the intraepithelial T cells expressing CD3 (an antigen associated with the T cell receptor) do not express the T cell subset antigens CD4 or CD8. Approximately 20% of CD7+ cells (T cells and null cells) do not express CD4 or CD8 and 14% of the CD7+ cells do not express CD3 and are therefore not T cells. The CD7+, CD3+/-, CD4-, CD8- population is concentrated in the tips of the villi. In coeliac disease, the ratios of the subsets change significantly. The percentage of CD3+, 4-, 8- cells increases to 28%, the proportion of CD7+, 4-, 8- cells remains unchanged and the CD7+, CD3- (non-T cell) population is reduced to 1.4% of the CD7+ cells. In contrast, in patients with villous atrophy of uncertain aetiology, all CD4-, CD8- lymphocyte subsets are decreased compared with normal biopsies. Finally, in enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine) in which the 'uninvolved mucosa' is histologically similar to untreated coeliac disease, the changes in the intraepithelial T cell sub-sets are indistinguishable from those in coeliac disease, suggesting that the lymphoma is a complication of coeliac disease.

Adult↗

Primary B cell gastric lymphoma. A genotypic analysis.

A series of cases of gastric lymphoproliferative disease exhibiting the features of pseudolymphoma, frank lymphoma, or both was investigated immunohistochemically and genotypically for evidence of B cell clonality. Immunoperoxidase studies on frozen and paraffin sections showed that all cases clearly exhibited immunoglobulin light chain restriction (eight cases kappa, six cases lambda). Southern blotting using JH, Ck, and Cl probes to detect clonally rearranged gene fragments confirmed monoclonality in each case, and the immunohistochemical and genotypic data were in agreement in all cases except one (1 light chain restriction/k gene rearrangement). The study confirmed that light chain restriction in gastric lymphoid infiltrates is synonymous with monoclonality ant there is a histologic continuum between low grade B cell gastric lymphoma with features of pseudolymphoma and high grade B cell lymphoma. The authors believe that histologic and immunohistochemical features such as light chain restriction clearly discriminate reactive and neoplastic gastric lymphoid infiltration. Therefore, light chain-restricted lymphoid proliferation, previously termed pseudolymphoma is, in fact, an early stage of frank lymphoma, which obviates the need to use the term pseudolymphoma.

B-Lymphocytes↗

The bcl-2 gene in primary B cell lymphoma of mucosa-associated lymphoid tissue (MALT).

The bcl-2 gene rearrangement representing t(14:18) chromosomal translocation is the most frequent karyotypic abnormality in non-Hodgkin's lymphomas of follicle center-cell lineage. By using three bcl-2 DNA probes, 21 cases of non-Hodgkin's B cell lymphoma arising from gastrointestinal mucosa and eight cases of follicular lymphomas were examined. No rearrangement of the gene could be detected in the group of gastrointestinal lymphomas, although it was identified in 75% of the follicular lymphomas. The findings suggest that these two groups of lymphomas are not a family at genetic level and support the earlier suggestion that B cell lymphomas arising from gastrointestinal mucosa-associated lymphoid tissue are not of follicle center-cell lineage.

Blotting, Southern↗