Diversified cell origin of
H
elicobacter 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 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.