Gastric Extranodal Marginal Zone B-cell Research Articles

Clinical Impact Assessment and Utilization Prospects of the t(11:18) Chromosomal Translocation in Gastric MALT Lymphoma in Koreans: A Single Center Retrospective Analysis

The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value= 0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.

Endoscopic Findings of Gastric Extranodal Marginal Zone B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma.

Endoscopic Findings of Gastric Extranodal Marginal Zone B-Cell Mucosa-Associated Lymphoid Tissue Lymphoma.

Treatment outcome of gastric extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type in the Hong Kong Chinese population: a single centre experience.

To analyze the clinical characteristics, treatment outcome of patients with gastric extra-nodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type (EMZBL-MALT). Data of 30 patients with gastric EMZBL-MALT diagnosed in Caritas Medical Center between July 1997 and June 2009 were analyzed retrospectively. The median follow-up time was 6.4 years [interquartile range (IQR) 3.9 to 8.9 years] and the median age at time of diagnosis was 71.5 years (IQR 64 to 81 years). All subjects, with investigations done for disease staging, suffered from localized disease (stage I or II1). Helicobacter infection was identified in 67% of subjects. Twenty Helicobacter-positive subjects received Helicobacter eradication treatment and seven Helicobacter-negative subjects received single-agent chemotherapy (cyclophosphamide), with disease remission rates at 85% and 71% respectively. Only one subject died apparently from disease progression. The 5-year and 10-year overall survival rates were 75% and 62.5% respectively. Helicobacter eradication and single-agent chemotherapy were effective treatment modalities for early stage gastric EMZBL-MALT with and without Helicobacter infection respectively. Survival was favorable.

From array-based hybridization of Helicobacter pylori isolates to the complete genome sequence of an isolate associated with MALT lymphoma

Backgroundelicobacter pylori infection is associated with several gastro-duodenal inflammatory diseases of various levels of severity. To determine whether certain combinations of genetic markers can be used to predict the clinical source of the infection, we analyzed well documented and geographically homogenous clinical isolates using a comparative genomics approach.ResultsA set of 254 H. pylori genes was used to perform array-based comparative genomic hybridization among 120 French H. pylori strains associated with chronic gastritis (n = 33), duodenal ulcers (n = 27), intestinal metaplasia (n = 17) or gastric extra-nodal marginal zone B-cell MALT lymphoma (n = 43). Hierarchical cluster analyses of the DNA hybridization values allowed us to identify a homogeneous subpopulation of strains that clustered exclusively with cagPAI minus MALT lymphoma isolates. The genome sequence of B38, a representative of this MALT lymphoma strain-cluster, was completed, fully annotated, and compared with the six previously released H. pylori genomes (i.e. J99, 26695, HPAG1, P12, G27 and Shi470). B38 has the smallest H. pylori genome described thus far (1,576,758 base pairs containing 1,528 CDSs); it contains the vacAs2m2 allele and lacks the genes encoding the major virulence factors (absence of cagPAI, babB, babC, sabB, and homB). Comparative genomics led to the identification of very few sequences that are unique to the B38 strain (9 intact CDSs and 7 pseudogenes). Pair-wise genomic synteny comparisons between B38 and the 6 H. pylori sequenced genomes revealed an almost complete co-linearity, never seen before between the genomes of strain Shi470 (a Peruvian isolate) and B38.ConclusionThese isolates are deprived of the main H. pylori virulence factors characterized previously, but are nonetheless associated with gastric neoplasia.

Clinicopathological comparison of the World Health Organization/Wotherspoon score to the Groupe d’Etude des Lymphomes de l’Adult grade for the post‐treatment evaluation of gastric mucosa‐associated lymphoid tissue lymphoma

The World Health Organization (WHO) has adopted criteria for the histological differential diagnosis of gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (GML) based on the criteria proposed by Wotherspoon in 1993 (WHO/Wotherspoon score). These histological criteria are commonly used by pathologists for initial diagnoses, but have not been adopted uniformly for the post-treatment evaluation of GML. In 2003, the Groupe d'Etude des Lymphomes de l'Adult (GELA) proposed a new histological grading system (GELA grade) in preference to use of the WHO/Wotherspoon score for post-treatment evaluation. In the present study, we compared the WHO/Wotherspoon and GELA systems to examine which histological criterion is better for post-treatment evaluation. Fourteen cases of GML under long-term follow up were initially diagnosed according to the WHO criteria with detailed immunohistology, and were periodically evaluated with both histological criteria after anti-Helicobacter pylori treatment. They were also evaluated based on histological stromal changes accompanying the disappearance of lymphoma tissue. The study showed strong similarities between the WHO/Wotherspoon and GELA systems and no clear advantage of either system for post-treatment evaluation. The GELA grade could not be used for the evaluation of changes in the degree of lymphoma infiltration from pre- to post-treatment because the four-item scale is not comparable with the formal six-point WHO/Wotherspoon scale. Stromal changes in the lamina propria, including an empty appearance and fibrosis, were correlated with lymphoma reduction after treatment and appear to be good indicators for post-treatment evaluation. We propose the utilization of the WHO/Wotherspoon score accompanied by the assessment of stromal changes for the post-treatment evaluation of GML.

T(11;18)(q21;q21) in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue in stomach: a study of 48 cases

Gastric extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MZL-MALT) is speculated to be immune mediated and is notable for responding to treatment by Helicobacter pylori eradication. However, the gastric MZL-MALT with t(11;18)(q21;q21) has been shown to be resistant to treatment by H. pylori eradication. We studied the molecular, immunohistochemical, and histological aspects of 48 cases of gastric MZL-MALT and used a reverse transcription real-time PCR assay to assess the presence of a t(11;18)(q21;q21) in formalin-fixed, paraffin-embedded tissue. Florescence in situ hybridization for t(11:18)(q21;q21) was used to confirm the real-time PCR results. Three distinct morphological subtypes were recognized: monocytoid, small lymphocytic, and plasmacytoid. Morphology, immunophenotype, and immunoglobulin heavy chain (IgH) gene rearrangement were correlated with the results of the t(11:18)(q21;q21) assay. Of the 48 analyzed cases, 15 (31%) were positive for t(11;18)(q21;q21) and 33 (69%) were monoclonal for IgH gene rearrangement. Of the 15, 13 (87%) cases with t(11;18)(q21;q21) translocation showed IgH gene rearrangement by PCR. Of the 33 t(11;18)(q21;q21)-negative cases tested, 20 cases (61%) showed IgH gene rearrangement. The 15 t(11;18)(q21;q21) translocation-positive cases had either monocytoid (12 of 15) or small lymphocytic morphology (3 of 15). Aberrant expression of CD43 was observed in 8 of 15 (53%) t(11;18)(q21;q21)-positive cases and 21 of 31 (68%) t(11;18)(q21;q21)-negative cases. Our data show that t(11;18)(q21;q21)-positive MZL-MALTs frequently show monocytoid morphology, less often small lymphocytic morphology, and not purely plasmacytoid morphology. Identification of a t(11;18)(q21;q21) by reverse transcription real-time PCR is highly specific for MZL-MALT and helps in the diagnosis of MZL-MALT. Studying the correlation between this translocation and morphological features may increase our understanding of the role of this translocation in the pathogenesis and the clinical behavior of gastric MZL-MALT.

Characteristics of magnified endoscopic images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue, including changes after treatment

The utility of magnifying endoscopy for diagnosis of epithelial tumors has been reported, but there are few reports for nonepithelial tumors. To determine the characteristics of magnified images of gastric extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) before and after treatment. This was a retrospective study. Endoscopy Unit, Hokkaido University Hospital. Eleven patients diagnosed with MALT lymphoma were enrolled. The microstructural pattern, collecting venules, and abnormal vessels in gastric MALT lymphoma were assessed before treatment and at 4 to 7 months after treatment by using magnifying endoscopy. MAIN OUTCOME MEASUREMENT AND RESULTS: The characteristics of magnified endoscopic images before treatment were the disappearance of gastric pits and the appearance of abnormal vessels. Ten cases of Helicobacter pylori-infected MALT lymphoma were treated by H. pylori eradication, and 1 H. pylori-negative case was treated by radiation therapy after eradication therapy. Ten patients achieved complete disease remission. After the treatment, recovery of gastric pits and subepithelial capillary network, and the disappearance of abnormal vessels were revealed by magnifying endoscopy. This was a small pilot study. Magnified findings of gastric MALT lymphoma before and after therapy seem to correlate with complete response and no response.

Gastric extranodal marginal zone B-cell lymphomas of MALT type exclusively express toll-like receptor 4 in contrast to other lymphomas infiltrating the stomach

BackgroundDevelopment and growth of extranodal marginal zone B-cell lymphomas (eMZBCLs) of mucosa-associated lymphoid tissue (MALT) type are thought to be highly dependent on Helicobacter pylori and autoantigens. Receptors mediating these effects are not characterised so far. Toll-like receptors (TLRs) recognise bacterial proteins and autoantigens, which results in inflammatory reactions and influences tumour development and growth. Materials and methodsTLR4, 5 and 9 expressions were evaluated by immunohistology and confocal microscopy in gastric eMZBCL in comparison to other lymphomas infiltrating the stomach. ResultsTLR4 was exclusively expressed on the cell surface in all eMZBCL (n = 19) and not in chronic lymphocytic leukaemia (CLL, n = 12) or mantle cell lymphoma (MCL, n = 10). TLR5 was strongly expressed in CLL and weak in some eMZBCL (15 of 19), but not in MCL. TLR4, 5 and 9 were negative in all the three lymphoma entities. ConclusionsExclusive TLR4 expression may enable eMZBCL to interact with H. pylori and autoantigens. Blockade of TLR4 might be a new approach for therapy of eMZBCL of MALT type.

Chromosome instability and translocation t(11;18) in primary gastric marginal zone B‐cell lymphoma of MALT‐type

The prognosis for patients with mucosa-associated lymphoid tissue (MALT) lymphomas is good; these tumours have usually an indolent course with overall survival rates that are greater than 80% at 5-year, but some rare cases with histological transformation in aggressive diffuse large cell lymphoma have also been diagnosed. Here, we present cytogenetic results on endoscopic bioptic material of 42 cases of primary gastric extranodal marginal zone B-cell lymphoma (EMZL) using fluorescence in situ hybridization (FISH) approach with API2, MALT1 and centromeric probes for chromosome 3 and 18, and their impact on the clinical outcome.