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T C Diss

Publications and source records attributed to T C Diss.

At least 19 recordsLinked to original sources
PubMed2001

Resistance of t(11;18) positive gastric mucosa-associated lymphoid tissue lymphoma to Helicobacter pylori eradication therapy.

20-30% of gastric mucosa-associated lymphoid tissue (MALT) lymphoma associated with Helicobacter pylori do not regress after antibiotic therapy. Regression can be assessed only by extended follow-up. To assess whether t(11;18, q21;q21), which results in a chimeric transcript between the AP12 and MLT genes, predicts lymphoma resistance to antibiotic therapy, we screened for the fusion transcript with RT-PCR in ten responsive and 12 non-responsive gastric MALT lymphomas. The AP12-MLT transcript was detected in nine (75%) of 12 patients non-responsive to antibiotic therapy but not in responsive patients. Most H pylori-associated gastric MALT lymphomas that do not respond to antibiotic therapy are associated with t(11;18, q21;q21).

Adult↗
PubMed2000

BCL10 gene mutation in lymphoma.

BCL10 is directly involved in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. Wild-type BCL10 promoted apoptosis and suppressed malignant transformation in vitro, whereas truncated mutants lost the pro-apoptotic activity and exhibited gain of function enhancement of transformation. We studied 220 lymphomas for genomic BCL10 mutation by polymerase chain reaction-single-strand conformational polymorphism and DNA sequencing. Nineteen mutations were found in 13 lymphoma specimens, as follows: 8 of 120 (6.7%) mucosa-associated lymphoid tissue (MALT) lymphomas, 4 of 42 (9.5%) follicular lymphomas, and 1 of 23 (4.3%) diffuse large B-cell lymphomas. No mutations were found in 14 mantle cell lymphomas or 21 T-cell lymphomas. High-grade MALT lymphoma tended to show a slightly higher mutation frequency (2 of 25, 8%) than low-grade MALT tumor (6 of 95, 6.3%). Among low-grade gastric MALT lymphoma, mutations were found in 3 of 11 tumors that did not respond to Helicobacter pylori eradication therapy, but none were found in 22 tumors that regressed completely after H pylori eradication. All 14 potentially pathogenic mutations were distributed in the carboxyl terminal domain of BCL10. Deletion accounted for 10 of these mutations; 10 of 14 mutations caused truncated forms of BCL10. Western blot analysis of a mutant case confirmed the presence of truncated BCL10 products of anticipated size. Our results suggest that BCL10 mutation may play a pathogenic role in B-cell lymphoma development, particularly in aggressive and antibiotic unresponsive MALT lymphomas, and may further implicate the biologic importance of the carboxyl terminal of the molecule. (Blood. 2000;95:3885-3890)

Adaptor Proteins, Signal Transducing↗
PubMed2000

Clone-specific PCR reveals wide dissemination of gastric MALT lymphoma to the gastric mucosa.

The development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori infection. Despite its indolent clinical course and prolonged localization to the site of origin, the lymphoma frequently presents with multifocal lesions. However, the true extent of tumour involvement in the gastric mucosa is unclear, since reactive appearing lymphocytic infiltrates are always present and could contain tumour cells that are not readily identifiable on cytological grounds. Gastrectomy specimens of four MALT lymphoma cases were studied by microdissection and clone-specific polymerase chain reaction (CS-PCR) and of a further case with t(1;14)(p22;q32) by immunohistochemistry for BCL10 protein, which acted as a tumour marker for tumour cells carrying the translocation. CS-PCR revealed that tumour cells were commonly present in histologically non-lymphomatous lymphocytic infiltrates microdissected from areas well separated from tumour lesions. Tumour cells were also frequently found in infiltrates microdissected from the resection margins. These findings were reinforced by direct identification of tumour cells, as recognized by strong BCL10 nuclear staining, in non-lymphomatous lymphocytic infiltrates in the case with t(1;14)(p22;q32). The results show that gastric MALT lymphoma disseminates widely within the gastric mucosa without necessarily forming diagnostic lesions.

Chromosomes, Human, Pair 1↗
PubMed1999

Simultaneous phenotypically distinct but clonally identical mucosa-associated lymphoid tissue and follicular lymphoma in a patient with Sjögren's syndrome.

A 44-year-old woman with a 12-year history of Sjögren's syndrome (SS) developed a low-grade mucosa-associated lymphoid tissue (MALT) lymphoma in the parotid gland. Two years later, she presented with generalized lymphadenopathy and hepatosplenomegaly and a follicular lymphoma was diagnosed. To investigate the relationship of the two histologically distinct lymphomas, we re-examined their histology and immunophenotype and studied the lymphomatous tissue from the parotid, cervical lymph node, and spleen using molecular genetic methods. Histologic and immunophenotypic studies confirmed the previous diagnoses and also identified a previously unnoticed focus of follicular lymphoma in the second parotid gland biopsy. Polymerase chain reaction (PCR) amplification of the rearranged Ig heavy-chain gene showed the same sized dominant product in the MALT lymphoma and the follicular lymphoma. Similarly, PCR analysis of the t(14:18) translocation yielded an identical sized band from both MALT and follicular lymphoma. Cloning and sequencing of the Ig PCR products showed an identical CDR3 sequence from each lesion, indicating a common clonal lineage. The follicular lymphoma of the parotid gland lymph node and the follicular lymphoma of the spleen showed an identical mutation signature to that of the salivary gland MALT lymphoma. We propose that follicular lymphoma in the parotid gland lymph node may have resulted from colonization of lymphoid follicles by MALT lymphoma cells, following which the tumor cells were induced to express a follicular lymphoma phenotype, due to Bcl-2 overexpression caused by t(14;18), leading to a change in clinical behavior resulting in rapid widespread dissemination of disease. These observations suggest that the distinct phenotypes of low-grade B-cell lymphomas may be the consequence of interplay between genetic and local microenvironmental factors.

Adult↗
PubMed1999

Mucosal intra-epithelial lymphocytes in enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population.

Loss of response to a gluten-free diet (refractory sprue) and ulcerative jejunitis are complications of celiac disease that may progress to enteropathy-associated T-cell lymphoma (EATL). Both conditions are characterized by the presence of a nonlymphomatous monoclonal T-cell population in the enteropathic mucosa. In EATL, a similar monoclonal population that shows clonal identity with the lymphoma itself is also present in the enteropathic mucosa. In this study we show that in all three circumstances the monoclonal T-cell population is constituted by cytologically normal, noninvasive intraepithelial T lymphocytes that share an identical aberrant immunophenotype with EATL. Patients with refractory sprue and/or ulcerative jejunitis are, therefore, suffering from a neoplastic T-cell disorder for which hematological treatment strategies need to be devised.

Celiac Disease↗
PubMed1999

Parvovirus B19 is associated with benign testes as well as testicular germ cell tumours.

AIMS: Parvovirus B19 has been demonstrated in testes of patients with germ cell tumours but not in controls, raising the possibility that the virus has an aetiological role in these tumours. The aims of this study were to investigate the association of the virus with germ cell tumours and to localise the virus histologically. METHODS: DNA was extracted from paraffin wax embedded sections of testes from 10 seminomas, eight teratomas, two mixed seminoma/teratomas, and 10 testes showing benign histology. Polymerase chain reaction (PCR) amplification of three regions within the NS and VP1/2 genes was carried out in duplicate on all samples. One PCR positive case (seminoma/teratoma) was examined by microdissection of histologically defined tissue components followed by PCR amplification of parvoviral sequences. Samples from PCR positive patients were immunostained using a B19 specific monoclonal antibody. RESULTS: Seven cases were PCR positive, these comprised two of 10 seminomas, one of two mixed tumours, none of eight teratomas, and four of 10 benign controls. PCR analysis of the material microdissected from the seminoma/teratoma showed the presence of the virus in regions of seminoma, teratoma, intratubular germ cell neoplasia, normal tubules, and connective tissue. All patient samples studied immunohistochemically were negative. CONCLUSIONS: This confirms the presence of parvovirus B19 in a proportion of germ cell tumours; however, in one patient, the virus was widespread in the tissue components and not confined to tumour cells. In addition, the virus was present in control benign testes. These data suggest that B19 might not be of aetiological importance in germ cell tumours of testis.

Adult↗
PubMed1998

Follicular lymphomas contain a clonally linked but phenotypically distinct neoplastic B-cell population in the interfollicular zone.

Follicular lymphomas are thought to arise from the follicle center B cells and are characterized by follicular structures that recapitulate many features of normal secondary lymphoid follicles. The neoplastic B cells of follicular lymphoma reside not only in follicles but also in the interfollicular zone in which they form a diffuse infiltrate. We have investigated the frequency, extent, and biological characteristics of this interfollicular component in 30 cases of follicular lymphoma. An interfollicular B-cell infiltrate of variable extent (minimal, moderate, or prominent) was present in all cases. Morphologically interfollicular neoplastic B cells were small centrocyte-like cells with lower grade cytology and lower proliferation fraction compared with the neoplastic follicles. The neoplastic phenotype of these cells (CD20+, light chain restricted) was confirmed in 18 cases. Clonal identity between the follicular and interfollicular components was shown in five cases using microdissection and PCR amplification of immunoglobulin heavy chain genes. Analysis of Ig heavy chain gene sequences showed identical variants of tumor subclones in both follicular and interfollicular compartments, indicating active tumor cell traffic between the two. In six cases in which frozen tissue was available, the immunophenotype of follicular and interfollicular tumor cells were compared using immunohistochemistry. Activation markers such as CD10, CD38, and CD95 and T-cell costimulatory molecules CD80 and CD86, which were expressed by neoplastic follicles, were either downregulated or absent in the interfollicular component in most of the cases. The low-grade cytological features, low proliferation fraction, and downregulation of activation markers in the interfollicular neoplastic B cells suggests that these are resting cells analogous to memory B cells of normal lymphoid tissues. The presence of such a resting tumor cell subpopulation in the majority of follicular lymphomas may partly account for the remarkable resistance to therapy of this disease.

Antigens, CD↗
PubMed1998

High frequency of CagA+ Helicobacter pylori infection in high-grade gastric MALT B-cell lymphomas.

A high incidence of Helicobacter pylori infection has been found in patients with gastric MALT (mucosa-associated lymphoid tissue) B-cell lymphoma. Recent studies have indicated that the aggressive strains of the bacterium containing the CagA gene may have direct effects on tumourigenesis. To investigate the involvement of CagA+ strains in MALT lymphomagenesis, a sensitive polymerase chain reaction (PCR)-based detection assay for the gene was developed. DNA extracts from paraffin sections of 123 H. pylori-related gastric biopsies from Italy were analysed, including 56 cases of chronic gastritis, 37 low-grade, and 30 high-grade MALT lymphomas: 30.3 per cent (17/56) of the gastritis cases, 37.8 per cent (14/37) of the low-grade, and 76.7 per cent (23/30) of the high-grade MALT lymphomas were found to contain the CagA gene. The frequency of CagA+ strain infection was significantly higher (P < 0.05) in high-grade than in low-grade MALT lymphoma or gastritis. These results suggest that high-grade gastric MALT lymphoma transformation may be more likely to occur following infection by CagA+ strains of H. pylori.

Antigens, Bacterial↗
PubMed1998

True histiocytic lymphoma: a morphologic, immunohistochemical, and molecular genetic study of 13 cases.

We describe the morphologic, immunohistologic, and genotypic characteristics of 13 cases of true histiocytic lymphomas. Six cases presented with primary gastrointestinal involvement, five with lymphadenopathy, the other sites involved being the bone marrow and the skin. The neoplastic cells displayed large abundant eosinophilic cytoplasm, occasionally vacuolated with folded or bizarre-shaped nuclei with prominent nucleoli. Mitotic figures were numerous. Multinucleated cells were common. The pattern of growth was usually diffuse and noncohesive. Spindle cell sarcoma-like areas were evident in five cases, with a prominent foam cell component in four cases. All cases expressed histiocyte-associated markers (CD68, lysozyme, alpha-1-antitrypsin), CD45 or CD45RO, and were negative for CD1a, epithelial, and B- and T-cell lineage-specific markers. Reactivity for S-100 was observed in a variable proportion of cells in 11 cases. The proliferation fraction varied from 3 to 88%. Genotypic analysis for T-cell receptor or immunoglobulin gene rearrangement demonstrated a germline configuration in all cases. We demonstrate that true histiocytic lymphoma is a rare distinctive pathologic entity that may be defined by immunohistochemical criteria and that recognition among histiocytic disorders is important for clinical and prognosis reasons.

Adult↗
PubMed1998

Enteropathy-associated T cell lymphoma with brain involvement.

In a patient with enteropathy-associated T cell lymphoma. there was dissemination to the brain manifesting as an inflammatory lesion. the intestinal and brain lesions were studied using routine histology, immunohistochemistry, and polymerase chain reaction. The jejunum was involved by a multifocal large cell lymphoma associated with multiple inflammatory ulcers and villous atrophy with crypt hyperplasia of the intervening mucosa. The lesion in the brain consisted of necrotic tissue associated with an infiltrate of histiocytes and a relatively scant infiltrate of primarily small lymphocytes. The appearance was that of an inflammatory rather than a neoplastic process. The intestinal lymphoma cells were positive for T cell markers and contained cytotoxic granules detected with the TIA-1 monoclonal antibody. The small lymphocytes and occasional large cells in the cerebral lesion showed the same immunophenotype. DNA extracted from the intestinal lymphoma and the cerebral lesion showed identical monoclonal rearrangement of the TCR-gamma gene. Dissemination from enteropathy-associated T cell lymphoma may masquerade as an inflammatory lesion. Molecular analysis is useful in confirming the diagnosis.

Aged↗
PubMed1997

Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone.

The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

Adult↗
PubMed1997

Clonality analysis in tumours of women by PCR amplification of X-linked genes.

Modifications have been made to two polymerase chain reaction (PCR) methods for clonality analysis based on the inactivation patterns of two highly polymorphic X-linked genes encoding the androgen receptor (AR) and monoamine oxidase A (MAOA). These methods have been used to examine the clonal nature of frozen tissues from 42 tumours and 25 non-tumour controls from female subjects. Unbalanced inactivation patterns of the genes, which indicate monoclonality, were frequently observed in tumours of heterozygous (informative) cases (18/35 = 51.4 per cent for the AR gene, 9/30 = 30 per cent for the MAOA gene, and 21/38 = 55.2 per cent for both). Among 23 informative non-tumour controls, only one (4.3 per cent), a reactive lymph node, showed skewing in the AR gene. Successful detection of monoclonality was found to depend on the proportion of tumour cells in the tissues examined. None of the AR or MAOA informative cases containing less than 50 per cent of tumour cells showed imbalance in inactivation patterns. With more than 50 per cent of tumour cells in the samples, 66.6 per cent (18/27) of AR and 39.1 per cent (9/23) of MAOA informative cases showed allelic imbalance, with a combined frequency of 72.4 per cent (21/29) of both genes. Our results demonstrate that the methods described are useful for clonal analysis of tissue samples from female patients.

Breast Neoplasms↗
PubMed1997

Epstein-Barr virus in B-cell lymphomas associated with chronic suppurative inflammation.

Chronic antigenic stimulation is considered to play an important role in neoplastic lymphoid transformation. This paper describes three cases of non-Hodgkin lymphomas (NHLs) associated with long-standing chronic suppuration. Two were primary bone lymphomas associated with long-standing chronic osteomyelitis and one was a primary skin lymphoma associated with chronic venous ulcers with a latent period of 13 years. All were diffuse large B-cell lymphomas, with plasmacytoid differentiation in two cases. Epstein-Barr virus (EBV)-encoded RNAs were demonstrated in virtually all tumour cells in all cases by in situ hybridization. Immunohistochemistry revealed EBV-encoded latent membrane protein (LMP)-1 expression in one case and BZLF1 protein expression in all three cases, whilst the EBV-encoded nuclear antigen (EBNA)-2 was not detected. Kaposi's sarcoma-associated herpesvirus (KSHV) sequences were absent in two cases studied. Our cases show similarities with pyothorax-associated pleural lymphomas reported mainly from Japan and recently from France, which are invariably associated with EBV. These findings suggest a causal effect of EBV in the development of this type of lymphoma complicating long-standing chronic suppuration. Localized immunodepression induced by chronic inflammation or immunosuppressive cytokines may favour the clonal proliferation of EBV-infected B cells.

Aged↗
PubMed1997

Composite mantle-cell lymphoma and plasmacytoma.

We report a case of a composite lymphoma comprising both mande cell lymphoma and a plasmacytoma. The two components were morphologically and immunohistochemically quite distinct. These properties, coupled with both direct and indirect molecular genetic evidence, suggest that these were two separate tumours occurring together by chance or by unknown oncogenic mechanisms, rather than clonally linked lymphomas.

Biomarkers↗
PubMed1997

Ongoing immunoglobulin gene mutations in mantle cell lymphomas.

Mantle cell lymphomas (MCL) frequently show a vaguely follicular growth pattern. This phenomenon is thought to result from the colonization of reactive B-cell follicles by tumour cells. In view of the unique property of the germinal centre environment, antigen stimulation may play a role in the expansion of the tumour. To assess this, we have examined ongoing Ig mutations, which are genetic markers of B cells in persistent response to antigen stimulation, in five MCLs including two cases derived from the gastrointestinal tract known as lymphomatous polyposis (LP). We have specifically analysed Ig ongoing mutations in tumour cells from multiple lesions in one case and in tumour cells microdissected from colonized follicles in two cases. The consensus Ig VB sequences in four MCLs were identical, or almost identical (three cases 100%, one case 99% homology), to the published germlines, which in each case were those frequently employed by autoantibodies. The consensus Ig VH sequence in the remaining case displayed 95.5% homology to the closest published germline. This may represent derivation from an unknown VH germline or a rare instance of somatic mutations. Extensive sequencing of the rearranged Ig genes revealed ongoing mutations within the tumour clone in two cases: one was a LP with multiple lesions of the gastrointestinal tract and the other was a nodal MCL in which tumour cells from colonized follicles were analysed. Our results indicate that MCLs are derived from pre-germinal centre B cells, possibly autoreactive B-cell clones. The ongoing mutations identified suggest a possible involvement of antigen stimulation in the clonal expansion of a proportion of MCLs.

Base Sequence↗
PubMed1997

Genetic evidence for a clonal link between low and high-grade components in gastric MALT B-cell lymphoma.

High-grade MALT lymphomas often contain low-grade tumour components; both cell populations have been shown to express the same immunoglobulin light chain previously. However, the clonal link between the low and high-grade components has not been established at the genetic level. To investigate this link, we have examined low- and high-grade components micro-dissected from tissue sections of four high-grade gastric MALT lymphomas. PCR and sequence analyses were performed to identify clone-specific rearranged immunoglobulin heavy chain gene sequences. In each of these cases, the PCR products from the two components were identical in size by electrophoresis. Direct sequencing revealed common clone-specific immunoglobulin heavy chain gene rearrangements in both lesions of each case, providing genetic evidence for a clonal link. These results support the proposal that high-grade MALT lymphomas generally evolve from low-grade clones.

Base Sequence↗
PubMed1997

The value of the polymerase chain reaction in the diagnosis of cutaneous T-cell infiltrates.

The distinction between reactive and neoplastic cutaneous T-cell infiltrates is difficult and requires good clinicopathologic correlation. Many cases manifest changes that are at the borderline between the two. The polymerase chain reaction (PCR) has been reported to detect monoclonality in 52-90% of cutaneous T-cell lymphomas and may be of use in the diagnosis of histologically borderline lesions. We have investigated the use of PCR in a series of borderline lesions including borderline biopsy samples from patients who subsequently developed cutaneous lymphoma. PCR amplification of T-cell receptor (TCR)-gamma chain gene was performed on formalin-fixed, paraffin-embedded tissue from 27 cases of clinically and histologically typical mycosis fungoides (MF), 22 borderline biopsy samples from 10 patients who subsequently developed MF (pre-MF), 32 clinically suspicious, histologically borderline lesions, and 31 cases of chronic dermatitis. Monoclonality was demonstrated in 16 of 27 (59%) cases of MF, 10 of 22 (50%) pre-MF biopsy samples (six of 10 patients), and six of 32 (19%) borderline biopsy samples. The same size monoclonal band was detected in pre-MF biopsy samples from six of seven patients in which a band was demonstrated in the diagnostic MF biopsy. Sequencing confirmed that the MF biopsy sample and the pre-MF biopsy sample contained the same clone. The 31 dermatitis cases gave rise to polyclonal PCR products. Monoclonality can be demonstrated using PCR in 59% of MF cases, which is comparable with other T-cell lymphomas and in up to 50% of borderline biopsy samples in patients who later develop lymphoma. Detection of T-cell monoclonality by PCR is strong evidence of an established or evolving cutaneous T-cell lymphoma.

Base Sequence↗