scholarly journals Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2993
Author(s):  
Barbara Kiesewetter ◽  
Christiane Copie-Bergman ◽  
Michael Levy ◽  
Fangtian Wu ◽  
Jehan Dupuis ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Signaling Pathways ◽  
Clinical Features ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Targeted Sequencing ◽  
Clinicopathological Parameters ◽  
Gastric Malt Lymphoma ◽  
Genetic Changes ◽  
H Pylori

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.

Association of T-Cell Regulatory Gene Polymorphisms With Susceptibility to Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

2006 ◽  
Vol 24 (21) ◽  
pp. 3483-3489 ◽  
Author(s):  
Tsu-Yao Cheng ◽  
Jaw-Town Lin ◽  
Li-Tzong Chen ◽  
Chia-Tung Shun ◽  
Hsiu-Po Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Crucial Role ◽  
Lymphoid Tissue ◽  
Gene Polymorphisms ◽  
Gastric Malt Lymphoma ◽  
H Pylori

Purpose Helicobacter pylori infection and host susceptibility interact to develop gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and activation of specific T cells might play a crucial role in this process. Recent investigations show that the CTLA4, CD28, and ICOS genes are located on chromosome 2q33 and their polymorphisms confer susceptibility to infectious and immune diseases through deregulation of T-cell stimulation. We aimed to determine the role of CTLA4, CD28, and ICOS polymorphisms in gastric MALT lymphoma. Patients and Methods Genotyping for CTLA4 (49 A/G, −318 C/T, and CT60 A/G), CD28 (IVS3+ 17T/C), and ICOS (c.602 A/C and c.1624C/T) was performed for 62 patients with gastric MALT lymphoma and compared with 250 unrelated healthy controls. Results H pylori infection was significantly higher in patients with gastric MALT lymphoma (90.3%) compared with controls (66.4%; P < .001). The CTLA4 −318 C/T genotype was associated with a lower risk of developing gastric MALT lymphoma (odds ratio [OR] = 0.3; P = .022), whereas CTLA4 49 G/G genotype was linked to a higher risk (OR = 4.1; P = .044). In patients with H pylori infection, CTLA4 49 G/G genotype was associated with an even higher risk (OR = 6.4; P = .047). Carriage of the tightly linked −318C –49G haplotype conferred a four-fold higher susceptibility to MALT lymphoma (OR = 4.2; P = .042). Complete remission after H pylori eradication was related to tumor stage but not to genotypes or haplotypes. Conclusion These results indicate a genetic link of CTLA4 gene polymorphisms to development of gastric MALT lymphoma and indirectly support the crucial role of host activated T cells in the MALT lymphomagenesis.

Low-grade gastric mucosa-associated lymphoid tissue lymphoma: Clinicopathological factors associated with Helicobacter pylori eradication and tumor regression.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 353-353
Author(s):  
Hyun Ik Shim ◽  
Dong Ho Lee ◽  
Jae Ho Cho ◽  
Cheol Min Shin ◽  
Hyuk Yoon ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Tumor Regression ◽  
Neutrophil Infiltration ◽  
Tumor Location ◽  
Gastric Malt Lymphoma ◽  
Low Grade ◽  
H Pylori

353 Background: Eradication of Helicobacter pylori is widely accepted as the initial therapy for low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma. The aim of this study was to assess the remission and relapse rates of low-grade gastric MALT lymphoma after H. pylori eradication and to identify the clinical factors affecting remission. Methods: We retrospectively analyzed 151 patients diagnosed with gastric MALT lymphoma from May 2003 to December 2018. Results: Of the 151 patients, 112 (74.2%) had an H. pylori infection. Total regression rates with eradication was 90.2% (101/112) in H. pylori-positive patients and 55% (11/20) in H. pylori-negative patients. Age, sex, tumor location, endoscopic findings, and the severity of mononuclear lymphocytes were not related to achieving successful initial H. pylori eradication and remission. However, patients with a smaller H. pylori burden ( p=0.030) and less neutrophil infiltration ( p=0.003) were more likely to achieve a successful initial H. pylori eradication. H. pylori ( p<0.001) and the burden ( p=0.020) were significantly related to remission of MALT lymphoma. Conclusions: The results show that H. pylori burden and neutrophil infiltration were inversely related to the success of the initial H. pylori eradication procedure and that the H. pylori burden was inversely related to the remission of MALT lymphoma.

scholarly journals Evaluation of the Association of Nine Helicobacter pylori Virulence Factors with Strains Involved in Low-Grade Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

2004 ◽  
Vol 72 (2) ◽  
pp. 880-888 ◽  
Author(s):  
Philippe Lehours ◽  
Armelle Ménard ◽  
Sandrine Dupouy ◽  
Bernard Bergey ◽  
Fréderique Richy ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Virulence Factors ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Gastric Lymphoma ◽  
Gastric Malt Lymphoma ◽  
Low Grade ◽  
H Pylori ◽  
Few Data

ABSTRACT Helicobacter pylori has been associated with the development of two malignant diseases: gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Although the cag pathogenicity island, especially the cagA gene, has been linked with adenocarcinoma, few data concerning H. pylori pathogenic factors involved in low-grade gastric MALT lymphoma are available. The goal of this study was to analyze the prevalence of and correlation between genes coding for seven H. pylori virulence factors (cagA, cagE, vacA, iceA, babA, hopQ, and oipA) and two novel adhesins (sabA and hopZ) by comparing a collection of 43 H. pylori strains isolated from patients with low-grade gastric MALT lymphoma to 39 strains isolated from age-matched patients with gastritis only. Our results show that taken individually, none of the nine genes tested can be considered associated with MALT strains and allow us to conclude that MALT pathogenesis is not linked with more proinflammatory H. pylori strains. We demonstrated that in patients infected with strains harboring the iceA1 allele, sabA functional status, and hopZ “off” status, the odds of developing a MALT lymphoma were 10 times higher. However, the low prevalence of such strains (10 of 43 MALT strains) renders this triple association a low-sensitivity marker for MALT strains. Our data confirmed that H. pylori virulence factors are correlated with one another. If the involvement of H. pylori in MALT lymphoma is well established, the pathomechanism by which gastric lymphoma occurs remains to be identified.

Long-Term Persistence of Monoclonal B Cells After Cure of Helicobacter pylori Infection and Complete Histologic Remission in Gastric Mucosa–Associated Lymphoid Tissue B-Cell Lymphoma

2001 ◽  
Vol 19 (6) ◽  
pp. 1600-1609 ◽  
Author(s):  
Christian Thiede ◽  
Thomas Wündisch ◽  
Birgit Alpen ◽  
Beatrix Neubauer ◽  
Andrea Morgner ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cells ◽  
Sequence Analysis ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Gastric Malt Lymphoma ◽  
Low Grade ◽  
H Pylori

PURPOSE: Cure of Helicobacter pylori infection is associated with remission induction in the majority of patients with low-grade gastric mucosa associated lymphoid tissue (MALT) lymphoma in localized stages; however, limited data exist as to whether these patients may be cured of their lymphoma. The present study was performed to investigate whether the polymerase chain reaction (PCR) for the rearranged immunoglobulin heavy chain region may be used to define “molecular” remission. PATIENTS AND METHODS: Ninety-seven patients who suffered from low-grade gastric MALT lymphoma stage IE were observed with central pathology and molecular biology after cure of H pylori infection. PCR was performed with the use of consensus primers for the framework regions 1, 2, and 3 and monoclonality was corroborated by sequence analysis. In selected cases, microdissection was performed to study the origin of the monoclonal B cells. RESULTS: Of the 97 patients, 77 obtained complete endoscopic and histologic remission (CR). Twenty of 44 patients with PCR monoclonality at diagnosis and with sufficient molecular follow-up displayed monoclonal bands for a median time of 20.5 months after CR (range, 0 to 50.4 months). These B cells were related to the original lymphoma clone by sequence analysis. Microdissection analysis identified basal lymphoid aggregates as the source of these monoclonal B cells. Local relapse occurred in and was observed by PCR in four patients. All four patients displayed monoclonal PCR before relapse, and three of these four showed ongoing PCR monoclonality throughout their course, indicating the persistence of malignant cells. CONCLUSION: Half of all patients with gastric MALT lymphoma show long-term PCR monoclonality up to several years after cure of H pylori infection and CR. Patients with monoclonal PCR should be observed closely, whereas long-term PCR negativity may indicate cure of the disease.

scholarly journals CXCR4 PET/MRI for follow-up of gastric mucosa-associated lymphoid tissue lymphoma after first-line H. pylori eradication

Blood ◽  
2021 ◽  
Author(s):  
Marius Mayerhoefer ◽  
Markus Raderer ◽  
Wolfgang Lamm ◽  
Michael Weber ◽  
Barbara Kiesewetter ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Control Group ◽  
Gastric Malt Lymphoma ◽  
First Line ◽  
Cell Counts ◽  
Standardized Uptake Values ◽  
H Pylori

Post-treatment evaluation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma currently relies on esophagogastroduodenoscopy with histological assessment of biopsies. Overexpression of the G-protein-coupled C-X-C chemokine receptor type 4 (CXCR4) has been previously observed in MALT lymphoma. The aim of this prospective study was to evaluate PET with the novel CXCR4 tracer [68Ga]Pentixafor as a potential alternative to follow-up biopsies for assessment of residual disease (non-complete remission (CR)) after first-line H. pylori (HP) eradication. Forty-six post-HP eradication [68Ga]Pentixafor-PET/MRI examinations of 26 gastric MALT lymphoma patients, and 20 [68Ga]Pentixafor-PET/MRI examinations of 20 control group patients without lymphoma, were analyzed. In the MALT lymphoma group, time-matched gastric biopsies were used as reference standard, and showed CR in six cases. Pooled examination-based accuracy, sensitivity, specificity, and positive and negative predictive value of [68Ga]Pentixafor-PET for detection of residual gastric MALT lymphoma at follow-up, were 97.0%, 95.0%, 100.0%, 100.0%, and 92.9%, respectively. Maximum and mean PET standardized uptake values showed moderate correlation with immunohistochemistry-based CXCR4+ cell counts, with correlation coefficients of r=0.51 and r=0.52 (P=0.008 and P=0.006). In conclusion, CXCR4 imaging with [68Ga]Pentixafor-PET may represent a promising test for assessment of residual gastric MALT lymphomas after HP eradication.

scholarly journals An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT) lymphoma following blunt abdominal trauma

2019 ◽  
Vol 12 (10) ◽  
pp. e230878
Author(s):  
Karim Nashed ◽  
Keith Lai ◽  
Tyler Stevens ◽  
Gareth Morris-Stiff
Keyword(s):  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Motor Vehicle ◽  
Large Mass ◽  
Vehicle Collision ◽  
Repeat Endoscopy ◽  
Multiple Biopsies ◽  
H Pylori

A 79-year-old woman presented to the emergency department following a motor vehicle collision. As part of her workup she underwent a CT scan which identified a large mass containing calcifications centred around the gastric antrum, and while being assessed she produced 500 mL of haematemesis. An endoscopy revealed an area of friable mucosa the nature of which was uncertain, and multiple biopsies revealed amyloid deposition and active Helicobacter pylori gastritis. Following review of imaging and pathology, a diagnosis of gastric mucosa-associated lymphoid tissue (MALT) lymphoma was established. She was treated with quadruple therapy for the H. pylori and at 6-month follow-up she is asymptomatic with repeat endoscopy revealing healing of the ulceration and no biopsy evidence of H. pylori or MALT.

scholarly journals Preferential Dissemination of B-Cell Gastric Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma to the Splenic Marginal Zone

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 4071-4077 ◽  
Author(s):  
Ming-Qing Du ◽  
Huai-Zheng Peng ◽  
Ahmet Dogan ◽  
Tim C. Diss ◽  
Haiqun Liu ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
B Cell ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Marginal Zone ◽  
Gastric Lymphoma ◽  
Gastric Malt Lymphoma ◽  
Lymphoma Cells ◽  
Marginal Zone B Cells ◽  
Clonal Identity

Abstract 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.

scholarly journals Helicobacter pylori–Negative MALT Lymphoma Presenting as a Massive Recurrent Gastrointestinal Hemorrhage

2020 ◽  
Vol 8 ◽  
pp. 232470962093716
Author(s):  
Prateek S. Harne ◽  
Samiran Mukherjee ◽  
Ted Achufusi ◽  
Dhruv Lowe ◽  
Divey Manocha
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Gastric Lymphoma ◽  
Hypovolemic Shock ◽  
Gastric Neoplasms ◽  
Gastric Malt Lymphoma ◽  
Primary Gastric Lymphoma ◽  
Life Threatening

Primary gastric lymphoma is rare, representing 5% of all primary gastric neoplasms. The presenting complaints of gastric mucosa-associated lymphoid tissue (MALT) lymphoma are usually nonspecific. However, life-threatening gastrointestinal bleeding from the stomach is unusual and sparsely reported. While studies reveal an indolent course, we present a case that presented with massive and recurrent hematemesis leading to hypovolemic shock secondary to endoscopically confirmed MALT lymphoma, which was treated with radiotherapy to achieve remission. She had no autoimmune diseases and tested negative for Helicobacter pylori. Our case emphasizes the importance of early diagnosis and timely intensive radiotherapy of a localized but aggressive gastric MALT lymphoma.

scholarly journals Radiotherapy for localized gastric mucosa–associated lymphoid tissue lymphoma: long-term outcomes over 10 years

2017 ◽  
Vol 58 (4) ◽  
pp. 537-542 ◽  
Author(s):  
Yu Ohkubo ◽  
Yoshihiro Saito ◽  
Hiroki Ushijima ◽  
Masahiro Onishi ◽  
Tomoko Kazumoto ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
Residual Disease ◽  
Distant Metastases ◽  
Gastric Malt Lymphoma ◽  
Long Term Outcomes ◽  
Abdominal Lymph Node

Abstract This study aimed to assess the long-term outcomes of radiotherapy in patients with localized gastric mucosa–associated lymphoid tissue (MALT) lymphoma. Twenty-seven patients with Stage I gastric MALT lymphoma were treated with radiotherapy from 1999 to 2010. The median age was 65 years (range: 31–84). Fifteen patients were Helicobacter pylori–negative. Thirteen patients were treated with definitive radiotherapy alone. The other 14 patients who had refractory or residual disease following a prior treatment received salvage radiotherapy. The median dose of the radiotherapy was 30 Gy in 20 fractions (range: 30–39.5 Gy). The median follow-up period was 121 months (range: 8–176 months). The 5- and 10-year overall survival rates for all patients were 92% and 87%, respectively. No patients died from MALT lymphoma. Three patients died of other diseases at 8, 33 and 74 months after radiotherapy (myocardial infarction, pneumonia and hepatocellular carcinoma, respectively). No cases of local recurrence were observed during the follow-up period. There were no serious late gastric, liver or kidney complications during a median follow-up period of over 10 years. Two patients remain alive with distant metastases: a lung metastasis and an abdominal lymph node metastasis at 104 months and 21 months after radiotherapy, respectively. Excellent long-term local control was observed in patients with localized gastric MALT lymphoma after radiotherapy. However, lifelong follow-up should be conducted to detect cases of late recurrence, especially distant metastases.

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