Lymphoma & related disorders
Mature B cell neoplasms
Large B cell lymphomas-special subtypes
LBCL with IRF4 rearrangement
Author: Jayalakshmi Balakrishna, M.D.
Editorial Board Member: Genevieve M. Crane, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 27 March 2019
Last staff update: 2 January 2025
Copyright: 2019-2025, PathologyOutlines.com, Inc.
PubMed Search: Large B cell lymphoma with IRF4 rearrangement OR lymphoma of Waldeyer ring
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Flow cytometry description | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Balakrishna J. LBCL with IRF4 rearrangement. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomairf4rearrangement.html. Accessed January 18th, 2025.
Definition / general
- Uncommon subtype of large B cell lymphoma characterized by strong expression of IRF4 / MUM1
- Commonly associated with IRF4 gene rearrangement
Essential features
- Children and young adults
- Lymph nodes of head and neck or Waldeyer ring are affected
- Diffuse, diffuse and follicular or follicular pattern
- Medium to large cells
- Germinal center B cell phenotype with diffuse IRF4 / MUM1 expression
- Most cases show IRF4 rearrangement
Terminology
- Lymphoma of Waldeyer ring
ICD coding
Epidemiology
- Rare subtype accounting for 0.05% of diffuse large B cell lymphomas
- Primarily affects children and young adults
- Age range: 4 - 79 years; median age: 12 years (Blood 2011;118:139)
- Equal gender incidence (Blood 2011;118:139)
Sites
- Lymph nodes of the head and neck (Blood 2011;118:139, Ann Oncol 2012;23:3143)
- Waldeyer ring (Blood 2011;118:139, Ann Oncol 2012;23:3143, Am J Surg Pathol 2013;37:333)
- Gastrointestinal tract (Blood 2011;118:139, Ann Oncol 2012;23:3143)
Pathophysiology
- Arises from germinal center B cells with rearrangement of the IRF4 gene on chromosome 6p25 resulting in IRF4 / MUM1 expression (Blood 2011;118:139, Virchows Arch 2016;468:141)
- Cytogenetically cryptic rearrangement of IRF4 and IgH loci (Blood 2011;118:139)
- Immunoglobulin light chain loci are rarely involved in the rearrangement
- BCL6 rearrangements and TP53 loss have also been reported (Blood 2011;118:139, Virchows Arch 2016;468:141)
Clinical features
- Isolated lymph node enlargement
- Tonsillar enlargement
Diagnosis
- Biopsy of the involved lymph node / tissue with immunophenotyping and confirmation using FISH analysis for IRF4 rearrangement
- Strong, diffuse positivity for IRF4 / MUM1 in neoplastic cells
- Young age of the patient, head and lymph node / Waldeyer ring location
Prognostic factors
- Favorable response to treatment with immunochemotherapy
Case reports
- 7 year old Chinese boy with IRF4 / MUM1 positive lymphoma with strong and extensive CD5 and CD10 positivity (Pediatr Blood Cancer 2017;64:311)
- 12 year old boy with large B cell lymphoma with IRF4 rearrangement in the unusual location of inguinal region (Indian J Pathol Microbiol 2018;61:271)
Treatment
- Responds well to chemoimmunotherapy with or without radiation
Gross description
- Involved lymph node / tonsil is enlarged
- Firm, fleshy homogenous mass
Microscopic (histologic) description
- Lymph node architecture is effaced with a diffuse, diffuse and follicular or follicular infiltrate (Blood 2011;118:139)
- Neoplastic follicles are large and arranged back to back with attenuated mantle zones (Blood 2011;118:139)
- Neoplastic cells are medium to large (Blood 2011;118:139)
- Open chromatin with small nucleoli (Blood 2011;118:139)
- Absent starry sky pattern and infrequent mitotic figures (Blood 2011;118:139)
Microscopic (histologic) images
Contributed by Jayalakshmi Balakrishna, M.D.
Diffuse pattern
Expansile follicles
Diffuse effacement
with medium
sized cells
Medium sized atypical lymphoid cells
Round to irregular nuclear contours and conspicuous nucleoli
Follicular pattern
CD20
BCL2
BCL6
MUM1
CD21
Positive stains
- Pan B cell markers: CD20, CD79a and PAX5 (Blood 2011;118:139)
- IRF4 / MUM1 strongly and diffusely positive (Blood 2011;118:139)
- BCL6 (Blood 2011;118:139)
- BCL2 and CD10 variably positive (Blood 2011;118:139)
- Ki67 proliferation rate is high (Blood 2011;118:139)
Flow cytometry description
- Low side light scatter and moderate forward light scatter
- Pan B cell markers and CD10 positive
- Surface immunoglobulin light chain positive with monoclonal pattern
Molecular / cytogenetics description
- IRF4 gene rearrangement (Blood 2011;118:139, Virchows Arch 2016;468:141)
- Most common partner gene is IgH (Blood 2011;118:139, Virchows Arch 2016;468:141)
- Rarely partner is immunoglobulin light chain genes (Blood 2011;118:139, Virchows Arch 2016;468:141)
- In a subset of cases, IRF4 translocation is not detected by the available techniques (cryptic)
- In such cases, IgH rearrangement may be detected (Blood 2011;118:139, Virchows Arch 2016;468:141)
- Breakpoints in the BCL6 locus seen in some cases (Blood 2011;118:139, Virchows Arch 2016;468:141)
Molecular / cytogenetics images
Contributed by Itziar Salaverria, Ph.D.
FISH break apart probe for IRF4
Sample pathology report
- Lymph node, left cervical, excision:
- Large B cell lymphoma with IRF4 rearrangement; see synoptic report
Differential diagnosis
- Pediatric type follicular lymphoma: serpiginous configuration of neoplastic follicles and starry sky pattern; responds well to local management and shows good prognosis
- Diffuse large B cell lymphoma, NOS, germinal center phenotype, MUM1+: older age group, diffuse growth pattern, worse prognosis
- Follicular lymphoma, grade 3: older age group, germinal center phenotype, t(14;18), poor prognosis
Additional references
- Auris Nasus Larynx 2019;46:114, Haematologica 2010;95:253, Ann Diagn Pathol 2005;9:340, Mod Pathol 1990;3:308, Head Face Med 2019;15:1, Oncotarget 2017;8:11544, Swerdlow: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, 2017, Jaffe: Hematopathology, 2nd Edition, 2017
Board review style question #1
An 8 year old boy has tonsillar enlargement. Which stain is most likely positive in the neoplastic cells?
- CD1a
- CD3
- MUM1
- TdT
Board review style answer #1
Board review style question #2
Which is the common partner gene of IRF4 in large B cell lymphoma with IRF4 rearrangement?
- BCL2
- c-Myc
- IgH
- IgK
Board review style answer #2
