Large B-cell lymphoma with IRF4 gene rearrangements: Differences in clinicopathologic, immunophenotypic and cytogenetic features between pediatric and adult patients

Large B-cell lymphoma (LBL) with interferon regulatory factor 4 (IRF4) rearrangement (LBL-IRF4), a provisional entity in the 2017 WHO classification, primarily arises in children and young adults and has a favorable prognosis. However, few studies have addressed the clinicopathologic and cytogenetic features of older adults with IRF4-rearranged B-cell lymphomas. From a database of all internal and external cases (08/01/2015 to 12/01/2020) on which interphase fluorescence in situ hybridization was performed at the Mayo Clinic, we identified 43 patients with B-cell lymphoma and IRF4 rearrangements. Consistent features included large cell morphology, expression of CD20, BCL6, and MUM1, and absence of MYC-R. All pediatric cases (n = 12) arose in Waldeyer's ring (WR), cervical lymph node (CLN), or bowel, and lacked BCL6-R and BCL2-R, and all but one showed classic morphology. Adults with WR, CLN, or bowel involvement (n = 22) were younger (median 32 years). Their lymphomas resembled pediatric cases morphologically and lacked BCL2-R, although 30% harbored BCL6-R (P = 0.043). Lymphomas that involved other anatomic sites (n = 9) arose in older adults (median 68 years; P = 0.002) and often showed atypical morphology (P < 0.001). All lacked BCL6-R and 2 of 4 harbored BCL2-R (P < 0.001). LBL-IRF4 - arising in WR, CLN, or bowel may represent a distinct clinicopathologic entity characterized by pediatric/younger adult age, classic morphology, and lack of BCL2-R. In contrast, B-cell lymphomas with IRF4-R that arise in other sites usually involve older adults, are often morphologically atypical and/or harbor BCL2-R, and may be more akin to diffuse LBL, not otherwise specified.