PMID- 36810796
OWN - NLM
STAT- MEDLINE
DCOM- 20230331
LR  - 20230331
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Print)
IS  - 0945-6317 (Linking)
VI  - 482
IP  - 3
DP  - 2023 Mar
TI  - Prevalence of IRF4 rearrangement in large B-cell lymphomas of the Waldeyer's ring 
      in adults.
PG  - 551-560
LID - 10.1007/s00428-023-03516-7 [doi]
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most common B-cell non-Hodgkin 
      lymphoma (B-NHL) in adults. These lymphomas are classified according to gene 
      expression profiling (GEP) into germinal center B-cell (GCB) and activated B-cell 
      type (ABC). Recent studies have suggested new subtypes of large B-cell lymphoma, 
      based on genetic and molecular alterations, among them is large B-cell lymphoma 
      with IRF4-rearrangement (LBCL-IRF4). We used fluorescence in situ hybridization 
      (FISH), GEP (using the DLBCL COO assay by HTG Molecular Inc), and next generation 
      sequencing (NGS) to comprehensively characterize 30 cases of LBCLs located in 
      Waldeyer's ring in adult patients and to identify LBCL-IRF4. FISH revealed breaks 
      of IRF4 in 2/30 cases (6.7%), BCL2 breaks in 6/30 cases (20.0%), and IGH breaks 
      in 13/29 cases (44.8%). GEP classified 14 cases each as GCB or ABC subtype, and 2 
      cases remained unclassified; this was concordant with the immunohistochemistry 
      (IHC) in 25/30 cases (83.3%). A subgrouping, based on GEP, was performed: group 1 
      included 14 GCB cases with the most frequent mutations in BCL2 and EZH2 in 6/14 
      cases (42.8%). The two cases with IRF4 rearrangement were assigned to this group 
      by GEP and showed IRF4 mutations, supporting the diagnosis of LBCL-IRF4. Group 2 
      included 14 ABC cases; the most frequent mutations were CD79B and MYD88 
      identified in 5/14 patients (35.7%). Group 3 included 2 unclassifiable cases in 
      which no molecular patterns were detected. Overall, LBCLs of Waldeyer's ring in 
      adult patients are a heterogeneous group, including LBCL-IRF4, which shares 
      several features with cases in the pediatric population.
CI  - (c) 2023. The Author(s).
FAU - Streich, Sebastian
AU  - Streich S
AUID- ORCID: 0000-0002-7334-1565
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Frauenfeld, Leonie
AU  - Frauenfeld L
AUID- ORCID: 0000-0003-4236-5799
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Otto, Franziska
AU  - Otto F
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Mankel, Barbara
AU  - Mankel B
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Bonzheim, Irina
AU  - Bonzheim I
AUID- ORCID: 0000-0002-7732-0788
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Fend, Falko
AU  - Fend F
AUID- ORCID: 0000-0002-5496-293X
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany.
FAU - Quintanilla-Martinez, Leticia
AU  - Quintanilla-Martinez L
AUID- ORCID: 0000-0001-7156-5365
AD  - Institute of Pathology and Neuropathology, Eberhard Karls University of Tubingen 
      and Comprehensive Cancer Center, University Hospital Tubingen, 
      Liebermeisterstrasse 8, 72076, Tubingen, Germany. 
      leticia.quintanilla-fend@med.uni-tuebingen.de.
LA  - eng
GR  - IZKF 2019.2/Medizinischen Fakultat, Eberhard Karls Universitat Tubingen/
PT  - Journal Article
DEP - 20230222
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (interferon regulatory factor-4)
SB  - IM
MH  - Child
MH  - Humans
MH  - B-Lymphocytes/pathology
MH  - In Situ Hybridization, Fluorescence
MH  - *Lymphoma, Large B-Cell, Diffuse/pathology
MH  - Prevalence
MH  - Proto-Oncogene Proteins c-bcl-2/genetics
PMC - PMC10033557
OTO - NOTNLM
OT  - Diffuse large B-cell lymphoma
OT  - IRF4 mutations
OT  - IRF4 rearrangement
OT  - Waldeyer's ring
COIS- The authors declare no competing interests.
EDAT- 2023/02/23 06:00
MHDA- 2023/03/25 06:00
PMCR- 2023/02/22
CRDT- 2023/02/22 14:57
PHST- 2023/01/17 00:00 [received]
PHST- 2023/02/08 00:00 [accepted]
PHST- 2023/02/07 00:00 [revised]
PHST- 2023/02/23 06:00 [pubmed]
PHST- 2023/03/25 06:00 [medline]
PHST- 2023/02/22 14:57 [entrez]
PHST- 2023/02/22 00:00 [pmc-release]
AID - 10.1007/s00428-023-03516-7 [pii]
AID - 3516 [pii]
AID - 10.1007/s00428-023-03516-7 [doi]
PST - ppublish
SO  - Virchows Arch. 2023 Mar;482(3):551-560. doi: 10.1007/s00428-023-03516-7. Epub 
      2023 Feb 22.