Primary Large B-Cell Lymphomas of Immune-Privileged Sites With IRF4 Rearrangement: Clinicopathological and Molecular Characterization.

Authors

Yuxiu Zhang, Anqi Li, Yimin Li, Lei Zhang, Lili Zhang, Lei Li, Yufeng Huang, Linlin Du, Jie Huang, Lei Dong, Haimin Xu, Binshen Ouyang, Hongmei Yi, Chaofu Wang, Yingyong Hou

Published in

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. Pages 101084. Sep 17, 2026. Epub Sep 17, 2026.

Abstract

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is an aggressive B-cell lymphoma arising in the central nervous system, vitreoretina, and testis, whereas the molecular features of IP-LBCL with IRF4 rearrangement (IP-LBCL-IRF4-R) remain poorly characterized. Here, we report seven cases of IP-LBCL-IRF4-R, all showing IRF4 rearrangement confirmed by fluorescence in situ hybridization. The cohort included six males and one female, with a median age of 58 years (range, 34-73 years); all patients were immunocompetent. Tumors involved the central nervous system (n = 4) and testis (n = 3). With a median follow-up of 10 months (range, 3-45 months), all patients were alive. Histologically, all IP-LBCL-IRF4-R cases showed diffuse proliferation of medium-to-large B cells with centroblast-like and/or immunoblast-like morphology. Immunophenotypically, one case was classified as the germinal center B-cell subtype and six as the non-germinal center B-cell subtype. Five cases showed BCL2/C-MYC double expression, and all seven cases were negative for Epstein-Barr virus-encoded small RNA. IRF4 rearrangement was detected in all seven cases by break-apart probes, and an IGH::IRF4 fusion was detected in only one case; three cases harbored BCL6 rearrangements, and no BCL2 or MYC rearrangements were detected. Next-generation sequencing identified recurrent mutations in IRF4 and PIM1 (6/7, 85.7% each), followed by MYD88 (5/7, 71.4%) and BTG1, CD79B, and LRP1B (3/7, 42.9% each). LymphGen 2.0 classified five cases as the MCD subtype and two as Other. Our study highlights IRF4 rearrangement as a rare genetic event in IP-LBCL and provides further insights into the molecular diversity of this entity.

PMID:
42754234
Bibliographic data and abstract were imported from PubMed on 18 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.