Bailey.Glen at 21:36, 4 December 2023

2023-12-04T21:36:22Z

← Older revision		Revision as of 16:36, 4 December 2023
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	==Cancer Category/Type==		==Cancer Category/Type==

	*[[Mature B-Cell Neoplasms]]		*[[HAEM4:Mature B-Cell Neoplasms]]

	==Cancer Sub-Classification / Subtype==		==Cancer Sub-Classification / Subtype==

Bailey.Glen at 18:53, 3 November 2023

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 ==Primary Author(s)==
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 ==Notes==
 <nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

Bailey.Glen: Created page with "==Primary Author(s)== Afia Hasnain, MBBS, PhD TOC ==Cancer Category/Type== Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subtype== *Large B-cell Lymphom..."

2023-11-03T18:15:29Z

Created page with "==Primary Author(s)== *Afia Hasnain, MBBS, PhD __TOC__ ==Cancer Category/Type== *Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subtype== *Large B-cell Lymphom..."

New page

==Primary Author(s)==

*Afia Hasnain, MBBS, PhD
__TOC__

==Cancer Category/Type==

*[[Mature B-Cell Neoplasms]]

==Cancer Sub-Classification / Subtype==

*Large B-cell Lymphoma (LBCL) with ''IRF4'' Rearrangement

==Definition / Description of Disease==

*Rare LBCL harboring ''IRF4'' gene rearrangement and involving head & neck lymphoid tissues typically in the pediatric age group<ref>{{Cite journal|last=Liu|first=Qingyan|last2=Salaverria|first2=Itziar|last3=Pittaluga|first3=Stefania|last4=Jegalian|first4=Armin G.|last5=Xi|first5=Liqiang|last6=Siebert|first6=Reiner|last7=Raffeld|first7=Mark|last8=Hewitt|first8=Stephen M.|last9=Jaffe|first9=Elaine S.|date=2013-03|title=Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/23108024|journal=The American Journal of Surgical Pathology|volume=37|issue=3|pages=333–343|doi=10.1097/PAS.0b013e31826b9b57|issn=1532-0979|pmc=3566339|pmid=23108024}}</ref><ref>{{Cite journal|last=Louissaint|first=Abner|last2=Ackerman|first2=Adam M.|last3=Dias-Santagata|first3=Dora|last4=Ferry|first4=Judith A.|last5=Hochberg|first5=Ephraim P.|last6=Huang|first6=Mary S.|last7=Iafrate|first7=A. John|last8=Lara|first8=Daniel O.|last9=Pinkus|first9=Geraldine S.|date=2012-09-20|title=Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement|url=https://pubmed.ncbi.nlm.nih.gov/22855608|journal=Blood|volume=120|issue=12|pages=2395–2404|doi=10.1182/blood-2012-05-429514|issn=1528-0020|pmid=22855608}}</ref><ref name=":0">{{Cite journal|last=Salaverria|first=Itziar|last2=Philipp|first2=Claudia|last3=Oschlies|first3=Ilske|last4=Kohler|first4=Christian W.|last5=Kreuz|first5=Markus|last6=Szczepanowski|first6=Monika|last7=Burkhardt|first7=Birgit|last8=Trautmann|first8=Heiko|last9=Gesk|first9=Stefan|date=2011-07-07|title=Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults|url=https://ashpublications.org/blood/article/118/1/139/28404/Translocations-activating-IRF4-identify-a-subtype|journal=Blood|language=en|volume=118|issue=1|pages=139–147|doi=10.1182/blood-2011-01-330795|issn=0006-4971}}</ref>
<references group="23108024" />

==Synonyms / Terminology==

*None

==Epidemiology / Prevalence <ref name=":1">{{Cite journal|last=de Leval|first=L.|last2=Bonnet|first2=C.|last3=Copie-Bergman|first3=C.|last4=Seidel|first4=L.|last5=Baia|first5=M.|last6=Brière|first6=J.|last7=Molina|first7=T. J.|last8=Fabiani|first8=B.|last9=Petrella|first9=T.|date=2012-12|title=Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study|url=https://pubmed.ncbi.nlm.nih.gov/22700993|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=23|issue=12|pages=3143–3151|doi=10.1093/annonc/mds150|issn=1569-8041|pmid=22700993}}</ref><ref name=":2">{{Cite journal|last=Chisholm|first=Karen M.|last2=Mohlman|first2=Jeffrey|last3=Liew|first3=Michael|last4=Termuhlen|first4=Amanda|last5=Cairo|first5=Mitchell S.|last6=Gross|first6=Thomas G.|last7=Perkins|first7=Sherrie L.|last8=Miles|first8=Rodney R.|date=2019-08|title=IRF4 translocation status in pediatric follicular and diffuse large B‐cell lymphoma patients enrolled in Children's Oncology Group trials|url=https://onlinelibrary.wiley.com/doi/abs/10.1002/pbc.27770|journal=Pediatric Blood & Cancer|language=en|volume=66|issue=8|doi=10.1002/pbc.27770|issn=1545-5009}}</ref>==

*Rare ~0.05% of LBCLs
*Median age 12 years
*Male ~ Female

==Clinical Features <ref name=":1" /><ref name=":2" />==

*Lymphadenopathy
*Tonsillar hypertrophy

==Sites of Involvement <ref name=":1" />==

*Head and neck lymph nodes
*Waldeyer ring
*Gastrointestinal tract

==Morphologic Features <ref name=":1" />==

*Medium to large sized neoplastic cells
*Chromatin is more open than seen in centrocytes
*Small basophilic nucleoli
*Follicular type: large neoplastic follicles are seen with a back-to-back growth pattern and absent or attenuated mantle zones
*Follicles lack serpiginous configuration and starry-sky pattern

==Immunophenotype <ref name=":2" /><ref>{{Cite journal|last=Sukswai|first=Narittee|last2=Lyapichev|first2=Kirill|last3=Khoury|first3=Joseph D.|last4=Medeiros|first4=L. Jeffrey|date=2020-01|title=Diffuse large B-cell lymphoma variants: an update|url=https://pubmed.ncbi.nlm.nih.gov/31735345|journal=Pathology|volume=52|issue=1|pages=53–67|doi=10.1016/j.pathol.2019.08.013|issn=1465-3931|pmid=31735345}}</ref>==

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD20, CD79a, PAX5, BCL6, MUM1
|-
|Positive (subset)||CD10, BCL2
|-
|Negative (universal)||PRDM1
|}

==Chromosomal Rearrangements (Gene Fusions) <ref name=":0" /><ref>{{Cite journal|last=Ramis-Zaldivar|first=Joan Enric|last2=Gonzalez-Farré|first2=Blanca|last3=Balagué|first3=Olga|last4=Celis|first4=Verónica|last5=Nadeu|first5=Ferran|last6=Salmerón-Villalobos|first6=Julia|last7=Andrés|first7=Mara|last8=Martin-Guerrero|first8=Idoia|last9=Garrido-Pontnou|first9=Marta|date=01 23, 2020|title=Distinct molecular profile of IRF4-rearranged large B-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/31738823|journal=Blood|volume=135|issue=4|pages=274–286|doi=10.1182/blood.2019002699|issn=1528-0020|pmc=6978155|pmid=31738823}}</ref>==

IG/IRF4 translocations activate the transcription of the ''IRF4'' gene resulting in increased expression of the IRF4/MUM1 protein. Translocations between ''IGH, IGL'', and ''IGK'' with ''IRF4'' have been described. Most common translocation partner is ''IGH'' with a cytogenetically cryptic t(6;14)(p25;q32) translocation, whereas, light chain variants are rare.

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|-
|t(6;14)(p25;q32)||IGH/IRF4
|der(14)||Most common
|-
|t(6;22)(p25;q11)||IGL/IRF4
|der(22)||Rare
|-
|t(2;6)(p12;p25)
|IGK/IRF4
|der(2)
|Rare
|}
==Characteristic Chromosomal Aberrations / Patterns==

''IRF4'' Rearrangement<ref name=":0" />

==Genomic Gain/Loss/LOH<ref>{{Cite journal|last=Salaverria|first=Itziar|last2=Martin-Guerrero|first2=Idoia|last3=Burkhardt|first3=Birgit|last4=Kreuz|first4=Markus|last5=Zenz|first5=Thorsten|last6=Oschlies|first6=Ilske|last7=Arnold|first7=Norbert|last8=Baudis|first8=Michael|last9=Bens|first9=Susanne|date=2013-02|title=High resolution copy number analysis of IRF4 translocation-positive diffuse large B-cell and follicular lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/23073988|journal=Genes, Chromosomes & Cancer|volume=52|issue=2|pages=150–155|doi=10.1002/gcc.22014|issn=1098-2264|pmid=23073988}}</ref>==

*One study using comparative genomic hybridization showed complex changes with gains of 7q32.1-qter, 11q22.3-qter, and Xq28 and losses of 6q13–16.1, 15q14–22.3, and 17p.
*TP53 point mutations were detected with a loss of 17p showing inactivation of TP53 in a subset of these cases.
*Further studies are needed to define the potential functional effect of these variants

==Gene Mutations (SNV/INDEL)<ref name=":3">{{Cite journal|last=Ramis-Zaldivar|first=Joan Enric|last2=Gonzalez-Farré|first2=Blanca|last3=Balagué|first3=Olga|last4=Celis|first4=Verónica|last5=Nadeu|first5=Ferran|last6=Salmerón-Villalobos|first6=Julia|last7=Andrés|first7=Mara|last8=Martin-Guerrero|first8=Idoia|last9=Garrido-Pontnou|first9=Marta|date=01 23, 2020|title=Distinct molecular profile of IRF4-rearranged large B-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/31738823|journal=Blood|volume=135|issue=4|pages=274–286|doi=10.1182/blood.2019002699|issn=1528-0020|pmc=6978155|pmid=31738823}}</ref>==

*These tumors have shown a distinct molecular profile characterized by frequent mutations in ''IRF4'' and NF-κB-related genes (''CARD11, CD79B'', and ''MYD88'') and overexpression of downstream target genes of the NF-κB pathway.
*SNV profile for LBCL-IRF4: Frequently mutated genes were ''IRF4'' (76%), ''CARD11'' (35%), and ''CCND3'' (24%)
*CNV profile for LBCL-IRF4: Frequent 17p/''TP53'' deletions (25%), without gene mutations, and gains of chromosome 7 (45%) and 11q12.3-q25 (35%).
*Further studies are needed to define the potential functional effect of these variants.

==Epigenomics (Methylation)<ref name=":2" /><ref name=":3" />==

*No recurrent epigenetic changes have been reported in literature.
*Further studies are needed to describe the role of epigenomics in this entity

==Genes and Main Pathways Involved<ref name=":3" />==

*''IRF4'' rearrangement with IGH locus detected in most cases
*Mutations in NF-κB-related genes, in particular the ''CARD11'' gene are responsible for overexpression of the NF-κB pathway

<br />

==Diagnostic Testing Methods<ref>{{Cite journal|last=Salaverria|first=Itziar|last2=Martin-Guerrero|first2=Idoia|last3=Burkhardt|first3=Birgit|last4=Kreuz|first4=Markus|last5=Zenz|first5=Thorsten|last6=Oschlies|first6=Ilske|last7=Arnold|first7=Norbert|last8=Baudis|first8=Michael|last9=Bens|first9=Susanne|date=2013-02|title=High resolution copy number analysis of IRF4 translocation-positive diffuse large B-cell and follicular lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/23073988|journal=Genes, Chromosomes & Cancer|volume=52|issue=2|pages=150–155|doi=10.1002/gcc.22014|issn=1098-2264|pmid=23073988}}</ref>==

*IG/IRF4 rearrangements
*Strong and diffuse MUM1 staining suggestive of this diagnosis
*Cryptic ''IRF4'' translocation are not detectable by cytogenetic techniques
*IRF rearrangements can be detected by IHC and FISH analysis

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)<ref name=":0" /><ref name=":2" />==

*'''Diagnostic:''' IG/IRF4 rearrangements are diagnostic and specific to this disease entity. Further studies on mutation profiling in these cases may help in defining parameters for risk stratification.

*'''Prognostic:''' Favorable outcome after treatment (combination immunochemotherapy with or without radiation)

==Familial Forms<ref name=":2" />==

*No familial form reported in literature.

==Other Information==

*None

==Links==

*None

==References==
(use "Cite" icon at top of page)
<references />
===EXAMPLE Book===

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4:Large B-cell Lymphoma with IRF4 Rearrangement - Revision history

Bailey.Glen at 21:36, 4 December 2023

Bailey.Glen at 18:53, 3 November 2023

Bailey.Glen: Created page with "==Primary Author(s)== *Afia Hasnain, MBBS, PhD __TOC__ ==Cancer Category/Type== *Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subtype== *Large B-cell Lymphom..."

Bailey.Glen: Created page with "==Primary Author(s)== Afia Hasnain, MBBS, PhD TOC ==Cancer Category/Type== Mature B-Cell Neoplasms ==Cancer Sub-Classification / Subtype== *Large B-cell Lymphom..."