<p>Prior studies of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) have mainly emphasized B-cell-intrinsic oncogenic mechanisms and the supportive role of T-cells. However, whether neoplastic B-cells’ microenvironment can reciprocally drive T-cell clonality or even promote T-cell neoplastic evolution remains poorly understood. Prompted by an index case where MALT lymphoma evolved into composite lymphoma with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), we systematically investigated T-cell receptor (TCR) gene rearrangements in 147 consecutive MALT lymphoma cases diagnosed between 2020 and 2023. TCR clonality was assessed using EuroClonality PCR assays and validated by next-generation sequencing (NGS). Clinicopathologic correlations and histologic spatial patterns of T- and B-cell distribution were evaluated. Monoclonal TCR rearrangement was detected in 16.3% (24/147) of MALT lymphomas. Among them, TCRG rearrangements were significantly enriched in pulmonary cases (25.0%) but were absent in gastric cases (<i>P</i> = 0.0002). Histologically, two distinct patterns of B-T cell distribution were identified. Pattern_1 showed extensive intermingling of B- and T-cells, whereas Pattern_2 displayed relatively segregated growth with limited spatial overlap between the two lineages. Monoclonal TCR rearrangements represent a nonrandom event in a subset of MALT lymphomas, suggesting an underappreciated active role for T-cells in tumor evolution. The preferential enrichment of TCRG rearrangements in pulmonary cases compared with gastric cases highlights site-specific immune milieus shaping T-cell clonality. Together with distinct B-T spatial interaction patterns, these findings support dynamic B-T cell crosstalk and potential multilineage evolution within the MALT lymphoma microenvironment.</p>

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Mucosa‐associated lymphoid tissue lymphoma with monoclonal T-cell expansion

  • Kang Jiang,
  • Qun Wang,
  • Yichen Liu,
  • Xiaojun Wang,
  • Wei Rao,
  • Tian Qiu,
  • Xuemin Xue,
  • Xiaoli Feng

摘要

Prior studies of marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) have mainly emphasized B-cell-intrinsic oncogenic mechanisms and the supportive role of T-cells. However, whether neoplastic B-cells’ microenvironment can reciprocally drive T-cell clonality or even promote T-cell neoplastic evolution remains poorly understood. Prompted by an index case where MALT lymphoma evolved into composite lymphoma with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), we systematically investigated T-cell receptor (TCR) gene rearrangements in 147 consecutive MALT lymphoma cases diagnosed between 2020 and 2023. TCR clonality was assessed using EuroClonality PCR assays and validated by next-generation sequencing (NGS). Clinicopathologic correlations and histologic spatial patterns of T- and B-cell distribution were evaluated. Monoclonal TCR rearrangement was detected in 16.3% (24/147) of MALT lymphomas. Among them, TCRG rearrangements were significantly enriched in pulmonary cases (25.0%) but were absent in gastric cases (P = 0.0002). Histologically, two distinct patterns of B-T cell distribution were identified. Pattern_1 showed extensive intermingling of B- and T-cells, whereas Pattern_2 displayed relatively segregated growth with limited spatial overlap between the two lineages. Monoclonal TCR rearrangements represent a nonrandom event in a subset of MALT lymphomas, suggesting an underappreciated active role for T-cells in tumor evolution. The preferential enrichment of TCRG rearrangements in pulmonary cases compared with gastric cases highlights site-specific immune milieus shaping T-cell clonality. Together with distinct B-T spatial interaction patterns, these findings support dynamic B-T cell crosstalk and potential multilineage evolution within the MALT lymphoma microenvironment.