Discordant lymphoma consisting of splenic marginal zone lymphoma and diffuse large B-cell lymphoma in a hepatitis B virus carrier suggests virus-associated lymphomagenesis.

BACKGROUND

Discordant lymphoma (DL) is a rare entity characterized by the synchronous occurrence of two distinct lymphoma subtypes in different anatomical sites. While some DLs reflect transformation from a common progenitor, others may arise from genetically unrelated clones. Clarifying the clonal relationship is critical to understanding DL pathogenesis. Whole-exome sequencing (WES) and B-cell receptor (BCR) repertoire analysis offer valuable insights, but comprehensive genomic studies in DL remain limited.

CASE: We present a 61-year-old male with hepatitis B surface antigen (HBsAg) positivity, diagnosed with SMZL from splenectomy and diffuse large B-cell lymphoma (DLBCL) from mesenteric lymph node biopsy. He achieved complete remission after R-CHOP and later relapsed with DLBCL in the cervical lymph nodes. Whole-exome sequencing revealed no shared somatic mutations between SMZL and DLBCL. BCR repertoire analysis also demonstrated distinct V-J gene usage, and cytogenetic analyses supported their independent origins. Notably, DLBCL harbored mutations in TP53, MTOR, and BCL6 rearrangement alterations previously associated with hepatitis B virus (HBV)-associated lymphomas.

DISCUSSION: Our multi-platform analysis supports the clonal independence of SMZL and DLBCL in this patient, suggesting that these two lymphomas arose independently despite developing concurrently. Chronic antigen stimulation and genomic integration from HBV may have contributed to dual lymphomagenesis through separate pathways. This case illustrates the potential role of HBV in driving distinct yet simultaneous B-cell neoplasms.