A rare case of large B-cell lymphoma with IRF4 rearrangement and concomitant 11q aberrations: a diagnostic pitfall in...

Over the past few decades, molecular features have become crucial in diagnosing and classifying large B-cell lymphomas (LBCLs), but overlapping features pose diagnostic challenges. We reported a 24-year-old male patient with B-cell lymphoma presenting concurrent IRF4 rearrangement and 11q aberrations, highlighting diagnostic challenges in molecular-era lymphoma classification. Histopathology showed diffuse lymphoid cell infiltration with a starry-sky pattern, resembling Burkitt lymphoma or high-grade B-cell lymphoma (HGBL). Immunophenotyping revealed CD20+ , CD10+ , BCL6+ , IRF4+ , and high Ki67 (> 90%), raising suspicion of HGBL with 11q aberration (HGBL-11q) or LBCL with IRF4 rearrangement (LBCL-IRF4-R). FISH confirmed IRF4 translocation, 11q23 gain, and 11q24 deletion, while MYC/BCL2/BCL6 rearrangements were absent. Next-generation sequencing (NGS) showed mutations in IRF4, PBRM1, and NF-κB/PI3K-AKT pathways-characteristic of LBCL-IRF4-R-with no high-frequency mutated genes in HGBL-11q (e.g., SMARCA4, PDE10A, GNA13, DDX3X). Moreover, the case presents multiple IRF4 mutations in line with previous observations on LBCL-IRF4-R. The patient achieved complete remission with R-CHOP therapy, aligning with LBCL-IRF4-R's favorable prognosis. This case underscores the need for integrated morphology, immunophenotyping, and NGS to resolve complex diagnostic challenges. It presents a key diagnostic pitfall where secondary 11q aberrations in LBCL-IRF4-R can mimic HGBL-11q, revealing limitations of current genetic algorithms and advocating for expanded molecular diagnostic criteria.