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PubMed2002

Compartment analysis of T cell receptor gamma--and immunoglobulin V(H) rearrangements by microdissection in patients with malt lymphoma and chronic gastritis with lymphatic hyperplasia.

The interpretation of clonality within H. pylori-associated gastritis and low-grade MALT lymphoma remains controversial. Due to the observation of MALT lymphoma regression after H. pylori eradication, new definitions concerning the border between benign reactive lesions and malignant gastric lymphoma are needed. Gene rearrangements for immunoglobulin heavy-chain in low-grade MALT lymphoma (N= 12) and H. pylori-associated chronic gastritis with lymphatic hyperplasia (N= 13) were analyzed by microdissection and polymerase chain reaction. Furthermore, T cell receptor-gamma chain rearrangements were analyzed by gene scan analysis. In 11 of 12 cases with initial low-grade MALT lymphoma, intraepithelial and subepithelial B cell rearrangements showed a restricted usage of the immunoglobulin heavy-chain 3. In H. pylori-associated chronic gastritis, the intraepithelial B cell compartment showed an oligoclonal the immunoglobulin heavy-chain rearrangement pattern with a predominance of VH3. The subepithelial compartment did not show any restrictive immunoglobulin heavy-chain gene usage. Additionally a mono- to oligoclonal rearrangement pattern of the T cell receptor-y chain was observed in low-grade MALT lymphoma, whereas an oligoclonal pattem was observed in chronic gastritis. Our data provide evidence that low-grade MALT lymphoma may start within the epithelium and subsequently infiltrate the subepithelial compartment. The observation of a mono- to oligoclonal TCR-gamma rearrangement suggests that an antigen selecting process also takes place within reactive T cells. Combining TCR-gamma gene scan analysis with IgH chain rearrangement analysis might help in discriminating between chronic gastritis and initial MALT lymphoma in questionable cases.

B-Lymphocytes↗
PubMed2006

Diagnostic role of 18F-FDG PET in gastric MALT lymphoma.

BACKGROUND: The aim of the study was to evaluate the usefulness of 18F-FDG-PET in patients with gastric lymphoma, in particular those affected by mucosa-associated lymphoid tissue (MALT) type and aggressive gastric non-Hodgkin's lymphoma (NHL). MATERIAL AND METHODS: The study group consists of 15 patients with a previous diagnosis of gastric NHL referred to our PET centres in Bologna Hospital and Rovigo Hospital, Italy, in the period 2003-2004. In 9/15 patients the subsequent histological evaluation was consistent with a gastric MALT lymphoma, while aggressive gastric NHL was diagnosed in the other 6/15. PET scan was carried out in patients with known active disease in order to stage or re-stage disease prior to treatment or in patients in complete clinical remission to monitor disease during follow up. Patients were considered in complete clinical remission if free from disease for at least 8 months after chemotherapy or surgery.18F-FDG PET was performed following standard procedures. RESULTS: Overall 18F-FDG-PET was true positive in all cases of gastric MALT and non-MALT aggressive NHL with known active disease, while no pathological 18F-FDG uptake was evident in the subjects who were in complete clinical remission. The degree of 18F-FDG uptake (mean SUVmax values) in MALT lymphoma was much less intense in comparison to aggressive gastric NHL, suggesting a prognostic role of SUV calculation in gastric lymphomas. CONCLUSION: Our data demonstrate the significant accuracy of 18F-FDG-PET in detecting active disease in gastric lymphoma of both MALT and non-MALT NHL type. A higher SUV value appears to be related to a more aggressive disease.

Adult↗
PubMed1994

[Properties of white sorghum diastatic malt].

Diastatic malt enzymes have potential to hydrolize pregelatinized starches releasing soluble sugars, lowering viscosity of slurries and allowing the use of high nutrient densities for preparation of cereal-based creams, baby food and drinks. Determination of the extent in which sorghum malt is able to develop desirable functional properties such as viscoty, water solubility and nutritional quality is fundamental. In this work the characteristics of a white sorghum during germination and the resulting malt were evaluated. "Dorado" white sorghum was germinated at 28 degrees C and 95% RH during 6 days in complete darkness, dried at 55 degrees C and ground to produce diastatic malt flour. Physicochemical, chemical, diastatic and nutritional characteristics of malt and its ability to liquify precooked flour slurries were determined. Maximum diastatic activity occurred at 3-4 days germination. Dry matter loss increased during germination at a rate of 2.7 percent units per day. Longer germination resulted in increased dry matter loss and decreased diastatic activity. Water solubility index of sorghum increased linearly during the first 5 days of germination probably caused by the production of soluble sugars and free amino acids. In vitro protein digestibility, lysine content and C-PER increased during germination. Sorghum malt was able to liquify precooked rice, wheat, oats or millet pastes (20% solids) in 5 min mixing at 30 degrees C. Utilization of malts with maximum diastatic activity are useful to liquify precooked cereal pastes or drinks and to increase the total solid contents and nutrient density while keeping the liquid properties of the product.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1993

[A clinicopathologic study of primary gastric lymphoma of B-cell type among the Japanese with special reference to low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)].

The most common primary site of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is the gastrointestinal tract, particularly the stomach. The relationship of MALT lymphomas, however, with the more commonly occurring large B-cell gastric lymphoma has not been directly discussed except in the report of Chan et al. (1990), which lacked clinical information regarding the behavior of these tumors. To elucidate the relationship between high-grade large-cell lymphoma and MALT lymphoma, we studied in detail the histopathological and clinicopathologic features with the survival date of 77 Japanese cases of primary gastric lymphoma (PGL) of B-cell type. Based on degree of morphologically recognizable low- or high-grade components of the tumor, PGL was divided into four types: 18 cases of pure MALT lymphoma (type I); 13 cases of MALT lymphoma with small area of high-grade lymphoma (type II); 22 cases of high-grade lymphoma with small areas of MALT lymphoma (type III); and 24 cases pure high-grade lymphoma (type IV). Corresponding to the differences in the histologic pictures of each type, there were differences in the gross appearance, pathologic stage (including depth of invasion) and prognosis. These data suggests that both MALT and high-grade lymphomas of the stomach belong to the same cell lineage and constitute a pathological spectrum and that the histological grouping of PGL is clinico-pathologically useful.

Adult↗
PubMed1997

The t(11;18)(q21;q21) chromosome translocation is a frequent and specific aberration in low-grade but not high-grade malignant non-Hodgkin's lymphomas of the mucosa-associated lymphoid tissue (MALT-) type.

Primary extranodal malignant non-Hodgkin's lymphoma arising from the mucosa-associated lymphoid tissue (MALT-type lymphoma) represents a subtype of B-cell lymphoid malignancies with distinct clinicopathological features and is often associated with a favorable prognosis. Unlike the situation in nodal non-Hodgkin's lymphoma of B-cell lineage, few data are still available concerning the chromosomal constitution of MALT-type lymphomas. Until now, cytogenetic data from 29 low-grade MALT lymphomas with karyotypic alterations have been reported from different institutions, and virtually no data were available for high-grade MALT-type lymphomas. We have analyzed the cytogenetics of 44 MALT lymphomas arising in the stomach, parotid gland, thyroid gland, lung, breast, and conjunctiva. Clonal chromosome aberrations have been detected in 13 of 20 (65%) low-grade and 20 of 24 (83%) high-grade tumors. More than half of the low-grade lymphomas with abnormal karyotypes (7 of 13 cases, 53%) displayed clonal t(11;18)(q21;q21), thus specifically associating this translocation with MALT-type lymphomas for the first time in a larger series. In contrast, t(11;18) was not found in a single case of 20 high-grade MALT-type lymphomas with abnormal karyotypes, nor were translocations t(14;18) or t(3;14), characterizing about 10-35% of primary nodal large cell lymphomas. Instead, these lymphomas were associated with t(8;14)(q24;q32) in three cases, frequent deletions in the long arm of chromosome 6, and partial or whole gains of chromosomes 3, 7, 17, 18, and 21.

Chromosome Aberrations↗
PubMed1997

c-myc gene abnormalities in mucosa-associated lymphoid tissue (MALT) lymphomas.

c-myc gene abnormalities associated with lymphomagenesis, including rearrangements and mutations in the regulatory region between exon I and intron I, have been studied in 54 MALT lymphomas (43 low and 11 high grade) and 36 nodal lymphomas (27 low and 9 high grade). By Southern blot analysis, none of the 54 MALT lymphomas but 2 of 36 nodal lymphomas had c-myc gene rearrangements. Defined tumour cell populations from all MALT lymphoma cases were isolated by microdissection from frozen tissue sections and analysed by polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) and direct sequencing for somatic mutations in the exon I/intron I region of the gene. Point mutations in this region were identified in nine cases of MALT lymphomas (7/43 = 16.2 per cent of low grade; 2/11 = 18.1 per cent of high grade). These mutations were located at either the exon I/intron I border of myc intron factor (MIF) binding sites, which are critical in the negative regulation of c-myc expression. Of the nodal lymphomas, only the two cases (5-6 per cent) with c-myc gene rearrangement showed scattered or clustered mutations. These results suggest that c-myc mutations in MALT lymphomas are unlikely to be associated with chromosome translocation, which is the main cause of somatic mutations observed in other types of lymphomas. The mutations involving the c-myc regulatory regions may play a pathogenetic role in at least a proportion of MALT lymphomas.

Base Sequence↗
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↗
PubMed2000

Gastric MALT lymphoma and its relationship to Helicobacter pylori infection: management and pathogenesis of the disease.

Chronic Helicobacter pylori infection is strongly associated with the development of primary gastric B cell lymphoma of MALT-type. Therapeutic decisions in primary gastric MALT lymphomas, e.g., the choice for gastric surgery or stomach-conserving treatments in the form of radio-, chemo-, or eradication therapy, should be based on an accurate histopathological diagnosis, grading and clinical staging. Primary gastric low-grade MALT-NHLs in an early clinical stage associated with H. pylori infection were shown to respond with complete remission in approximately 77% of cases upon successful cure of the infection as only treatment modality. The effect of curing H. pylori infection on the course of a high-grade gastric MALT lymphoma is largely uncertain but preliminary results indicate a possible benefit for patients with high-grade MALT lymphoma upon eradication therapy. Concerning the pathogenetic mechanisms of lymphomagenesis, there are many questions to be addressed in the near future. In general, it is still unclear what the exact mechanisms are which lead to the malignant transformation of a reactive infiltrate. Is there a molecular-genetic or immunological point of no return? What is the biological significance of the immunoglobulin rearrangement detected with PCR? The wave of new data each year about the role of H. pylori in gastric MALT lymphoma might help that many of these questions addressed above might be answered within the next years.

Gastric Mucosa↗
PubMed2005

Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is usually associated with a chronic inflammatory disease from which lymphoid tissue of MALT type arises as a prerequisite for lymphoma proliferation. No well-characterized chronic inflammatory process has been identified in the larynx. METHODS: We report a case of primary MALT lymphoma of the larynx associated with extraesophageal reflux, chronic laryngitis, and gastric Helicobacter pylori infection, raising the issue of its physiopathology and treatment. RESULTS: Treatment of this MALT lymphoma of the larynx consisted of complete surgical excision associated with omeprazole, amoxicillin, and clarithromycin. No evidence of disease was observed after 24 months of follow-up. CONCLUSIONS: We may assume that chronic laryngitis could be a precursor to MALT lymphoma. This case is the first one to our knowledge of a primary MALT lymphoma of the larynx treated with conservative management combining surgical excision, reflux therapy, and eradication of gastric H. pylori infection.

Humans↗
PubMed1982

Expression of malT, the regulator gene of the maltose region in Escherichia coli, is limited both at transcription and translation.

Six mutations, which lead to an increase in malT expression, were mapped by sequencing techniques. All of them had one or other of two base changes. Determination of the transcription start point by reverse transcriptase mapping localised the two base changes with respect to the elements that control malT expression. One of the base changes ( malTp1 ) is located in the Pribnow box of the promoter, and presumably results in an increase in the rate of transcription initiation. The other ( malTp7 ) is located in the Shine and Dalgarno sequence, which precedes the malT cistron. It probably created a more favourable ribosome binding site on malT mRNA. A correlate of these observations is that the promoter and the ribosome binding site are both inefficient in a wild-type malT gene. A malTp1 malTp7 double mutant was constructed, which produced equivalent to 30 times more MalT protein than the wild-type strain.

Bacterial Proteins↗
PubMed1994

Mucosa-associated lymphoid tissue (MALT) in the human conjunctiva.

The recent description of conjunctival lymphomas with features of lymphomas that arise in mucosa-associated lymphoid tissue (MALT) infers the presence of MALT in the human conjunctiva. Some authors suggest that organized MALT is found in the normal human conjunctiva, but others disagree. In order to resolve this problem, we have examined the conjunctival fornix from unselected autopsies with no prior history of conjunctival or ocular disease for the presence of organized MALT. In only 31 per cent of cases was organized lymphoid tissue found with the morphological and immunophenotypic features of MALT. This finding suggests that MALT is not found in the normal human conjunctiva but is acquired during life in a proportion of apparently asymptomatic individuals.

Adolescent↗
PubMed2003

[Extranodal non-Hodgkin's lymphoma of MALT-type stage I. A case report].

BACKGROUND: Extranodal non-Hodgkin's lymphoma are mostly localized in the gastrointestinal tract. A small number of these lymphoma arise from specialized lymphoid cells, the so-called mucosa-associated lymphoid tissue (MALT). We describe one case with a metachronous occurrence of a MALT-type lymphoma of the conjunctiva of both eyelids and supraglottic larynx. PATIENT AND METHOD: A 56-year old woman was first treated in August 1990 for a low-grade B-cell lymphoma in the conjunctiva of the left eyelid. 42 months later an extranodal B-cell lymphoma, located in the conjunctiva of the right eyelid, was found. After a father period of 48 months a MALT-type lymphoma arose in the supraglottic larynx. The findings of staging examinations were normal. The final diagnosis was low-grade B-cell lymphoma of the MALT-type, limited to the conjunctival eyelids and supraglottic larynx, with the clinical staging of IE A. Treatment consisted of a LASER-resection followed by a locoregional radiotherapy, with the dose of 40 Gy. RESULTS: Currently no evidence of disease (NED) at all sites can be proven. CONCLUSIONS: Extranodal, primary low grade B-cell MALT-type lymphoma are rare. In the literature only few cases of each larynx- and conjunctival eyelid involvement described. The radiotherapy has been reported to achieve a long time of relapse-free interval. The present case demonstrates, that even the recurrence of an extranodal, primary low-grade B-cell MALT-type lymphoma responds well to local radiotherapy and can also have a long period of no evidence of disease.

Diagnosis, Differential↗
PubMed2003

Decreased frequency of HLA-B35 in patients with gastric MALT lymphoma.

Persistent infection with Helicobacter pylori has been shown to be strongly associated with the development of low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, the prevalence of H. pylori infection exceeds the incidence of MALT lymphoma by far. This discrepancy might at least partially be explained on a genomic basis of the host. To evaluate the association between HLA type and MALT lymphoma, we investigated 46 patients with MALT lymphoma recruited in a prospective multicenter study from October 1998 to March 2001. Over 13,000 voluntary stem cell donors from over 40 German blood banks represented the control group. Exploratory statistical analysis using Fisher's exact test showed significantly decreased frequency of HLA-B35 in the MALT lymphoma group compared to the control group. Our data suggest a negative association between HLA-B35 and MALT lymphoma; however, larger studies are necessary to confirm a protective role of this HLA antigen.

Adult↗
PubMed1998

[Diagnostic value of stomach biopsy in comparison with surgical specimen in gastric B-cell lymphomas of the MALT type].

Diagnostic und therapeutic management of gastric lymphomas of the mucosa-associated lymphoid tissue type (MALT-type lymphomas) is often based exclusively on the evaluation of biopsy material. To evaluate the diagnostic value of gastric biopsies in gastric MALT-type lymphomas, biopsies--on average six per patient--and subsequent surgical specimens of 64 patients were compared at the Institute of Pathology, University of Würzburg. Tumor diagnosis and tumor gradind were assessed. Using biopsy specimens, primary gastric MALT-type lymphomas were correctly diagnosed by local pathologists in 69% of cases, but correctly graded as low-grade, high-grade or secondary high-grade lymphomas in only 41%. When immunohistochemistry and molecular biological techniques were applied in addition to conventional histology, diagnosis of gastric MALT-type lymphoma was achieved in biopsies in 95% of cases at the Institute of Pathology Würzburg, but correct grading in only 73%. In secondary high-grade MALT-type lymphomas, both components--the high-grade and the low-grade component--were identified in gastric biopsies in only 33% of cases. Diagnostic accuracy in gastric lymphomas based on biopsies is limited by biopsy artefacts, but improved by using immunohistochemistry and molecular biological techniques. Particularly in secondary high-grade MALT-type lymphomas the correct diagnosis is often missed when using biopsies, due to a low number of biopsy specimens.

Biomarkers, Tumor↗
PubMed2005

Update on MALT lymphomas.

Gastric mucosa associated lymphoid tissue (MALT) lymphoma is a histologically distinct tumour derived from MALT acquired as a result of Helicobacter pylori infection. Eradication of H. pylori causes clinical regression of the lymphoma in 75% of cases. In seeking to identify those cases resistant to this therapy, and in the interests of further understanding the biology of MALT lymphoma, genetic alterations of MALT lymphomas have been investigated. Three translocations, t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21) are specifically associated with MALT lymphoma and the genes involved have been identified. T(11;18) results in a chimeric fusion between the API2 and MALT1 genes and is specifically associated with gastric MALT lymphomas that do not respond to eradication of H. pylori. T(1;14) and t(14;18) deregulate BCL10 and MALT1 expression, respectively. These three chromosomal translocations that involve different genes appear to share common oncogenic properties by targeting the same nuclear factor kappa B (NF kappa B) oncogenic pathway.

Humans↗
PubMed1999

Exclusive detection of the t(11;18)(q21;q21) in extranodal marginal zone B cell lymphomas (MZBL) of MALT type in contrast to other MZBL and extranodal large B cell lymphomas.

Extranodal mucosa-associated lymphoid tissue (MALT)-type lymphomas and nodal and splenic marginal zone B cell lymphomas (MZBL) share morphological and immunophenotypic features with marginal zone B cells of reactive lymphoid tissues. Although displaying a similar immunophenotype, recent investigations suggest fundamental genetic differences among these subgroups. To determine the prevalence of the t(11;18) in a larger series of MALT-type lymphomas and to investigate a possible occurrence in other lymphomas, we screened 106 non-Hodgkin's lymphomas (NHL) by interphase cytogenetics using yeast artificial chromosome (YAC) probes flanking the breakpoint at 11q21. A signal constellation indicating a disruption in 11q21 and thus pointing to the presence of the t(11;18) was observed in 9 of 33 (27%) low-grade lymphomas of MALT type. The complete absence of t(11;18)-positive cells in 32 primary and secondary extranodal high-grade lymphomas suggests that low-grade lymphomas of MALT type characterized by the t(11;18) are unlikely to transform into high-grade tumors. The absence of tumor cells carrying the t(11;18) in nodal MZBL challenges the assumption that most, if not all, of these tumors represent the nodal manifestation of a so far undetected low-grade lymphoma of MALT type. The t(11;18) was not detected in a single case of 29 splenic MZBL investigated. This observation strengthens the view that splenic MZBL are biologically different from extranodal MZBL of MALT type.

Chromosome Banding↗
PubMed1997

MALT-type lymphoma of the stomach is associated with Helicobacter pylori strains expressing the CagA protein.

BACKGROUND & AIMS: Helicobacter pylori is considered to be involved in the pathogenesis of gastric lymphoma of mucosa-associated lymphoid tissue (MALT) type. Strains expressing the CagA protein (CagA+ strains) have been strongly associated with severe gastritis, duodenal ulceration, and gastric adenocarcinoma. The aim of this study was to determine the presence of H. pylori as well as incidence of CagA+ strains in gastric MALT-type lymphoma. METHODS: Sera of 68 patients with gastric MALT-type lymphoma (22 with low grade, 36 with high grade, and 10 with secondary high grade) were obtained, and the serological response to CagA was studied by immunoblotting using a purified recombinant CagA protein, a CagA+ strain, and the corresponding isogenic CagA- mutant. RESULTS: Of the patients with MALT-type lymphoma, 98.5% (67 of 68 patients) were H. pylori seropositive. In the only seronegative patient, the bacterium was detected histologically by Warthin-Starry staining. Of the seropositive patients, 95.5% had serum immunoglobulin G antibodies to CagA compared with 67% of an H. pylori-positive control group (33 of 49 patients; P = 0.000037) with chronic active gastritis. CONCLUSIONS: These results indicate infection of almost all patients with MALT-type lymphoma by CagA+ H. pylori strains. Strains expressing the CagA protein seem to play a crucial role in the pathogenesis of gastric MALT-type lymphoma.

Adult↗
PubMed1999

Impaired T-cell regulation of B-cell growth in Helicobacter pylori--related gastric low-grade MALT lymphoma.

BACKGROUND & AIMS: Neoplastic B cells of the Helicobacter pylori-related low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma are responsive to T helper cells and sensitive to withdrawal of H. pylori-induced T-cell help. METHODS: The clonal progeny of T cells from the gastric mucosa of 5 patients with MALT lymphoma was compared with that of T-cell clones obtained from 5 H. pylori-infected patients with chronic gastritis. RESULTS: T-cell clones were assessed for specificity to H. pylori, cytokine profile, help for B-cell proliferation, and perforin- or Fas-mediated cytotoxic regulation of B-cell growth. Twenty-eight of 165 CD4(+) gastric clones from MALT lymphoma and 33 of 178 CD4(+) clones from chronic gastritis recognized H. pylori antigens. Cytokine production was similar in the 2 series of clones. All MALT lymphoma-derived clones dose-dependently increased their B-cell help, whereas clones from chronic gastritis lost helper activity at T-to-B-cell ratios greater than 1 because of concomitant cytolytic killing of B cells. T-cell clones from MALT lymphoma had both reduced perforin-mediated cytotoxicity and poor ability to induce Fas-mediated apoptosis. These defects were limited to gastric T cells. CONCLUSIONS: H. pylori-induced T cell-dependent B-cell activation and deficient cytotoxic control of B-cell growth may link H. pylori infection, local T-cell response, and genesis of low-grade gastric MALT lymphoma.

Aged↗