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Diversified cell origin of Helicobacter pylori eradication-responsive gastric diffuse large B-cell lymphomas.

Sung-Hsin Kuo·Kun-Huei Yeh·Chung-Wu Lin·Li-Tzong Chen·Jyh-Ming Liou·Chia-Tung Shun·Hsiao-Wei Lee·Ming-Feng Wei·Hsiu-Po Wang·Ming-Shiang Wu·Ann-Lii Cheng
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Abstract

A significant proportion of gastric diffuse large B-cell lymphoma with mucosa-associated lymphoid tissue [DLBCL(MALT)] and without MALT ('pure' DLBCL) can be resolved by Helicobacter pylori eradication (HPE). Gastric MALT lymphoma is an indolent lymphoma derived from memory B cells in the marginal zone. In the present study, we aimed to explore the origin of large cells in HPE-responsive gastric DLBCLs (complete remission after HPE). We investigated gastric lymphoma biopsies from 31 patients with HPE-responsive DLBCLs [15 'pure' DLBCLs, 16 DLBCL(MALT)s]. We used the Hans algorithm (CD10, BCL-6, and MUM1) to define the origins of germinal center B cell (GCB) and non-GCB. To further ascertain the cellular origin, 11 'pure' DLBCLs were examined using an Agilent whole-human genome microarray. Eleven DLBCLs [eight with 'pure' DLBCL and three with DLBCL(MALT)] were also assessed using Lymph2Cx. Specific GCB markers, including BACH2, AID, and BCL2 rearrangement and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) codon 641 mutations, were evaluated in 31 patients with HPE-responsive gastric DLBCLs. According to the Hans algorithm, 53% (8/15) of gastric 'pure' DLBCLs and 50% (8/16) of DLBCL(MALT)s were of the GCB phenotype. Gene expression assays revealed that five of six patients with 'Hans' GCB had GCB genetic signatures, whereas four of five patients with 'Hans' non-GCB had activated B-cell genetic signatures. The Lymph2Cx assay revealed the GCB subtype in seven of eight patients with 'Hans' GCB. The expression patterns of BACH2 (p = 0.005) and AID (p = 0.038) closely correlated with the 'Hans' GCB phenotype. BCL2 rearrangements and EZH2 codon 641 mutations were detected in 44% (7/16) and 13% (2/16) of patients with 'Hans' GCB, respectively. In another cohort of 29 HPE-unresponsive gastric DLBCLs [19 'pure' DLBCLs and 10 DLBCL(MALT)s], we found a close association between the 'Hans' GCB subtype and the GCB subtype as determined by the Agilent whole-human genome microarray and Lymph2Cx in lymphoma cells of these patients. In conclusion, more than half of HPE-responsive large cell lymphoma cases in the stomach were of GCB origin. © 2026 The Pathological Society of Great Britain and Ireland.

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HumansLymphoma, Large B-Cell, DiffuseStomach NeoplasmsHelicobacter pyloriMaleFemaleMiddle AgedHelicobacter InfectionsAgedGerminal CenterAdultLymphoma, B-Cell, Marginal ZoneBiomarkers, TumorMutationGene Expression ProfilingEnhancer of Zeste Homolog 2 ProteinAged, 80 and overAnti-Bacterial AgentsPhenotypeB-LymphocytesTreatment OutcomeAIDBACH2BCL2 rearrangementDLBCLEZH2 codon 641 mutationantibiotics responsivenesscell origingerminal center B cellstomachJournal Article

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Sung-Hsin Kuo, Kun-Huei Yeh, Chung-Wu Lin, Li-Tzong Chen, Jyh-Ming Liou, Chia-Tung Shun, Hsiao-Wei Lee, Ming-Feng Wei, Hsiu-Po Wang, Ming-Shiang Wu, Ann-Lii Cheng. 2026-08-05. Diversified cell origin of Helicobacter pylori eradication-responsive gastric diffuse large B-cell lymphomas.. https://doi.org/10.1002/path.70091

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