Large B-cell lymphoma with IRF4 rearrangement: clinicopathologic heterogeneity across the age spectrum

Large B-cell lymphoma with IRF4 rearrangement (IRF4-R LBCL) is a rare entity recognised in the current WHO-HAEM5 classification and the International Consensus Classification (ICC).

This study aimed to evaluate the clinicopathologic and fluorescence in situ hybridisation (FISH) findings of IRF4-R LBCL across a broad age spectrum.

Seven cases diagnosed with IRF4-R LBCL at the Department of Pathology, Hacettepe University Faculty of Medicine, were retrospectively reviewed. Clinical, morphological, immunohistochemical, and FISH findings were evaluated.

Patients' ages ranged from 13 to 77 years; three were aged 40 years or older. Cases under 40 years of age were localised to the head and neck region and gastrointestinal tract, and all remained in remission. In contrast, cases aged 40 years or older demonstrated more heterogeneous anatomical distribution and clinical behaviour, with one disease-related death during follow-up. Immunohistochemical analysis showed CD20 and MUM1/IRF4 positivity in all cases, whilst CD10, BCL6, and BCL2 expression was variable. IRF4 rearrangement was identified in all cases. MYC and BCL2 rearrangements were absent in all cases, whereas BCL6 rearrangement was detected in one adult patient and could not be assessed in one case.

Consistent with the literature, IRF4-R LBCL in children and young adults generally shows a favourable clinical course and characteristic clinicopathologic features. In adult patients, however, greater clinicopathologic and cytogenetic heterogeneity, including occasional additional abnormalities such as BCL6 rearrangement, may be observed. Accurate identification of IRF4 rearrangement is critical for differential diagnosis and may also have implications for clinical management, particularly when interpreted in conjunction with patient age and clinicopathologic features.