IRF4-Rearranged Large B-Cell Lymphoma on Waldeyer’s Ring: A Case Report

cases of CLL with DM were reported, and one patient received methotrexate with cyclophosphamide. The skin rash in DM does not mean malignant skin involvement; therefore, DM treatment should be initiated separately, as in our case. However, DM with associated malignancy responds poorly compared to idiopathic cases [5]. Long-term outcomes of CLL with DM are unknown, and so are data regarding the use of chemoimmunotherapy in such patients, although rituximab has shown efficacy in DM [6]. It is prudent for the overworked clinician to not overlook neurological or musculoskeletal symptoms in CLL patients, and a keen search for hematological malignancy is justified in known cases of inflammatory myopathies.


To the Editor,
Large B-cell lymphoma (LBCL) with IRF4 rearrangement is a newly recognized and rare entity. LBCL is characterized by coexpression of MUM1 and BCL6. It has been associated with young age and a favorable outcome. Most patients present with predominantly Waldeyer's ring or neck or head lymph node involvement [1,2,3]. Here, we present a case of LBCL with IRF4 rearrangement in an older male.
A 67-year-old man was admitted to the hospital with sore throat, dysphagia, and a lump in the right cervical region. Physical examination showed that the right palatine tonsil was enlarged and there was 2 cm of cervical lymphadenopathy unilaterally. After one week of antibiotic therapy, the lymphadenopathy still persisted. The patient underwent an excisional lymph node biopsy, which was consistent with LBCL of germinal center type, with a mainly follicular and focally diffuse pattern. The immunohistochemistry panel was positive for CD20 (clone L26; Scytek), CD10 (clone 56C6; Biocare), bcl-6 (clone LN22; Biocare Medical), and MUM1 (clone BC5; Biocare Medical), while bcl-2 (clone 124; Scytek) and myc (clone MYC; Biocare) were negative ( Figure 1A). Different from follicular lymphoma and diffuse large B-cell lymphoma, the neoplasm was mainly composed of centroblast-like large cells with germinal center phenotype and strong co-expression of MUM1. Morphologic and immunohistochemical findings reminded us of the possibility of IRF4-rearranged LBCL. FISH analysis for IRF4 rearrangement (IRF4, DUSP22 dual-color break-apart probe) was performed and rearrangement was found to be positive ( Figure 1B). Based on these findings, LBCL with IRF4 rearrangement was diagnosed. PET-CT showed increased FDG uptake on the right tonsil with level IIA-III cervical stations ( Figure 1C). Clinical staging studies led us to stage I disease and the International Prognostic Index score was calculated as 1. After four cycles of R-CHOP 21 , PET-CT showed complete remission ( Figure 1C). No further therapy was indicated, and 3 months after the chemotherapy, no evidence was observed of any recurrence.
Salaverria et al. [1] studied 720 lymphomas and screened a group of 427 cases for IRF4. They identified 20 lymphomas with proven IG/IRF4 fusion with a median age of 12 years. The IRF4positive lymphomas mostly presented as limited disease in the head and neck region, especially in Waldeyer's ring, and were associated with better prognosis [1].
Ramis-Zaldivar et al. [4] studied 20 LBCL-IRF4 pediatric and young adult cases with a median age of 14 years. Eight patients had nodal involvement of the head and neck region, and 8 had tonsillar involvement. Fifteen patients had complete remission after therapy without evidence of relapse for up to 99 months in follow-up; thus, a very favorable outcome was shown among LBCL-IRF4 cases [4].
Older age is considered to be an adverse prognostic factor in patients with Waldeyer's ring non-Hodgkin lymphoma and as an independent risk factor for inferior survival among patients with diffuse large B-cell lymphoma [3,5]. FLYER study results showed that four cycles of CHOP chemotherapy had the same effect among young patients with aggressive B-cell lymphoma who had favorable risk profile and stage I-II disease [6]. Our patient had no other risk factors except his age, and he had IRF4 gene arrangement; thus, we ended the chemotherapy after the fourth cycle with negative PET-CT results. Financial Disclosure: This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sectors.