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.

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.

scholarly journals Novel Insights of Lymphomagenesis of Helicobacter pylori-Dependent Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 547 ◽  
Author(s):  
Sung-Hsin Kuo ◽  
Ming-Shiang Wu ◽  
Kun-Huei Yeh ◽  
Chung-Wu Lin ◽  
Ping-Ning Hsu ◽  
...  
Keyword(s):  
T Cells ◽  
Helicobacter Pylori ◽  
B Cells ◽  
Gastric Mucosa ◽  
B Cell ◽  
Malt Lymphoma ◽  
Lymphoid Tissue ◽  
B Cell Lymphoma ◽  
Gastric Malt Lymphoma ◽  
First Line

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most common subtype of gastric lymphoma. Most gastric MALT lymphomas are characterized by their association with the Helicobacter pylori (HP) infection and are cured by first-line HP eradication therapy (HPE). Several studies have been conducted to investigate why most gastric MALT lymphomas remain localized, are dependent on HP infection, and show HP-specific intratumoral T-cells (e.g., CD40-mediated signaling, T-helper-2 (Th2)-type cytokines, chemokines, costimulatory molecules, and FOXP3+ regulatory T-cells) and their communication with B-cells. Furthermore, the reason why the antigen stimuli of these intratumoral T-cells with tonic B-cell receptor signaling promote lymphomagenesis of gastric MALT lymphoma has also been investigated. In addition to the aforementioned mechanisms, it has been demonstrated that the translocated HP cytotoxin-associated gene A (CagA) can promote B-cell proliferation through the activation of Src homology-2 domain-containing phosphatase (SHP-2) phosphorylation-dependent signaling, extracellular-signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), B-cell lymphoma (Bcl)-2, and Bcl-xL. Furthermore, the expression of CagA and these CagA-signaling molecules is closely associated with the HP-dependence of gastric MALT lymphomas (completely respond to first-line HPE). In this article, we summarize evidence of the classical theory of HP-reactive T-cells and the new paradigm of direct interaction between HP and B-cells that contributes to the HP-dependent lymphomagenesis of gastric MALT lymphomas. Although the role of first-line HPE in the treatment of HP-negative gastric MALT lymphoma remains uncertain, several case series suggest that a proportion of HP-negative gastric MALT lymphomas remains antibiotic-responsive and is cured by HPE. Considering the complicated interaction between microbiomes and the genome/epigenome, further studies on the precise mechanisms of HP- and other bacteria-directed lymphomagenesis in antibiotic-responsive gastric MALT lymphomas are warranted.

Ongoing somatic mutations and clonal expansions after cure of Helicobacter pylori infection in gastric mucosa-associated lymphoid tissue B-cell lymphoma.

1998 ◽  
Vol 16 (12) ◽  
pp. 3822-3831 ◽  
Author(s):  
C Thiede ◽  
B Alpen ◽  
A Morgner ◽  
M Schmidt ◽  
M Ritter ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cells ◽  
Gastric Mucosa ◽  
B Cell ◽  
Lymphoid Tissue ◽  
Somatic Mutations ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
H Pylori

PURPOSE Although most patients with primary gastric low-grade mucosa-associated lymphoid tissue (MALT) B-cell lymphoma experience complete endoscopic and histologic remission after the cure of Helicobacter pylori infection, in many patients, the polymerase chain reaction (PCR) still detects monoclonal B cells in the gastric mucosa. The present study asked whether the lymphoma immunoglobulin VH (IgVH) sequences remained stable in patients with gastric MALT lymphoma after H pylori eradication. PATIENTS AND METHODS Eight patients with stage EI disease treated with H pylori eradication were analyzed before and at different time points after the cure of the infection. After the amplification of IgVH genes from DNA extracted from gastric biopsy specimens, monoclonal PCR products were cloned and multiple clones (43 to 105) were sequenced per patient. RESULTS Mutations were detected in all lymphoma VH sequences, which suggested germinal center or postgerminal center origin of the lymphoma B cells. In five of the eight patients, clonal heterogeneity was observed at diagnosis or during follow-up. Genealogical analysis of shared and unshared mutations showed that the process of somatic mutations was ongoing after H pylori eradication in four of the five patients who showed clonal instability. Ongoing mutations were observed in three of the four patients who completely responded to H pylori eradication, but in only one of the four patients who did not respond or who partially responded. CONCLUSION In low-grade gastric MALT lymphomas, an ongoing process of somatic hypermutation and antigen selection can be detected after the therapeutic removal of the underlying stimulus H pylori. These data point to the relevance of yet unknown antigens that drive this disease. In addition, they challenge the view that these lymphomas may be cured solely by the eradication of H pylori.

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.

scholarly journals MALT lymphoma: epidemiology, clinical diagnosis and treatment

2018 ◽  
Vol 11 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Petruta Violeta Filip ◽  
◽  
Denisa Cuciureanu ◽  
Laura Sorina Diaconu ◽  
Ana Maria Vladareanu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
Malt Lymphoma ◽  
Cell Lymphoma ◽  
Gastric Lymphoma ◽  
Eradication Therapy ◽  
B Cell Lymphoma ◽  
Gastric Malt Lymphoma ◽  
H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

Long-term follow-up of patients with low-grade gastric MALT lymphoma after eradication of helicobacter pylori

2000 ◽  
Vol 118 (4) ◽  
pp. A764
Author(s):  
In Sung Song ◽  
You Sun Kim ◽  
Il Ju Choi ◽  
Joo Sung Kim ◽  
Hyun Chae Jung ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Malt Lymphoma ◽  
Gastric Malt Lymphoma ◽  
Low Grade ◽  
Long Term Follow Up

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.

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