IRF4 translocation status in pediatric follicular and diffuse large B‐cell lymphoma patients enrolled in Children's Oncology Group trials

Abstract

Large B‐cell lymphoma with IRF4 rearrangement is a provisional entity in the 2017 World Health Organization classification. In order to characterize these lymphomas in children from the United States, IRF4 FISH and immunohistochemical stains were performed on 32 follicular lymphoma and diffuse large B‐cell lymphoma (DLBCL) from Children's Oncology Group studies. Two DLBCLs (6%) had IRF4 rearrangements, one involving the ileocecal valve and another involving the tonsil and cerebrospinal fluid. Both cases had strong, diffuse IRF4/MUM1 immunohistochemical staining, which may be a pathologic clue to the diagnosis. Reclassification of these cases may have prognostic and therapeutic implications.

Distinct molecular profile of IRF4-rearranged large B-cell lymphoma

“…LBCL-IRF4 was recently recognized as a specific entity genetically characterized b IRF4 translocation, clinical presentation localized in the head and neck or abdominal regions, and a favorable outcome after chemotherapy. 17,19 We have now expanded these observations to show that these tumors have a distinct molecular profile characterized by frequent mutations in IRF4 and NF-kB-related genes (CARD11, CD79B, and MYD88) and overexpression of downstream target genes of the NF-kB pathway. These findings are intriguing, because most of these tumors have a GC phenotype and gene expression profile, whereas mutations in these genes and NF-kB activation have mainly been found in ABC-DLBCL in adults.…”

“…15,16 LBCL with IRF4 rearrangement (LBCL-IRF4) predominates in pediatric population, has a favorable outcome after therapy, and consistently expresses IRF4 due to translocation. [17][18][19][20] These cases display a complex pattern of chromosomal changes, but their mutational profile and possible relationship to other LBCLs is not known. 21 The last WHO classification has also recognized the category of HGBCL that encompasses a spectrum of morphological appearances from blastoid to cases with intermediate features between BL and DLBCL.…”

Diffuse large B-cell lymphoma variants: an update

“…45 A few cases are reported involving sites below the diaphragm. 46 Patients with follicular neoplasms often have indolent disease and an excellent prognosis following excision; chemotherapy may not be needed.…”

Experience with provisional WHO‐entities large B‐cell lymphoma with IRF4‐rearrangement and Burkitt‐like lymphoma with 11q aberration in paediatric patients of the NHL‐BFM group

“…First described by our group in 2011 2 and 2014 3 , both entities are mature B non‐Hodgkin lymphomas (B‐NHL) and are mostly found in children and adolescents; they are hence highly relevant to paediatric haematologists and oncologists. After their initial description, only a few patient series of these provisional entities have been published 4,5 . The prevalence of LBCL‐ IRF4 and mnBLL,11q among paediatric B‐NHL has also not been studied systematically.…”