IRF4 rearrangement may predict favorable prognosis in children and young adults with primary head and neck large B‐cell lymphoma

Purpose Large B‐cell lymphoma with IRF4 rearrangement (LBCL, IRF4+) has been recently recognized as a specific entity that is frequently associated with young age and favorable prognosis. However, whether the good outcome of the disease is due to IRF4+ or other factors remains obscure. We thus analyzed 100 young patients with primary head and neck LBCL to see the clinicopathologic correlates of IRF4+. Methods The histopathology, immunophenotype, IRF4 status of the tumors, and clinical data were reviewed. Results Twenty‐one tumors were diagnosed as LBCL, IRF4+, which were more frequently associated with a follicular growth pattern, medium‐sized blastoid cytology, germinal center B‐cell‐like, and CD5+ phenotype, compared with IRF4− ones. While most of the patients received chemotherapy with or without radiation, eight IRF4+ patients received mere surgical resection of the tumor and exhibited excellent outcome. IRF4+ cases featured a significantly higher complete remission rate, and better survivals compared with IRF4− ones. Multivariate analysis confirmed IRF4+ correlates with a better survival. Conclusion Our work confirmed the unique clinicopathologic features of LBCL, IRF4+, and disclosed for the first time the independent favorable prognostic impact of IRF4+. These findings may further unravel the heterogeneity of LBCL occurring in youth, and aid in risk stratification and tailoring the therapeutic strategy. The rearrangement of IRF4 gene not only defines a group of LBCL with distinct clinicopathologic features, but also is of practical implications for prognosis prediction and therapeutic strategy decision.