Bailey.Glen at 18:54, 3 November 2023

2023-11-03T18:54:06Z

@@ Line 1: / Line 1: @@
 {{Under Construction}}
 ==Primary Author(s)*==
@@ Line 158: / Line 163: @@
 ==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 "{{Under Construction}} ==Primary Author(s)*== Manando Nakasaki, MD, PhD (University of California, Irvine) Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvi..."

2023-11-03T18:17:31Z

Created page with "{{Under Construction}} ==Primary Author(s)*== Manando Nakasaki, MD, PhD (University of California, Irvine) Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvi..."

New page

{{Under Construction}}
==Primary Author(s)*==

Manando Nakasaki, MD, PhD (University of California, Irvine)

Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvine)

__TOC__

==Cancer Category/Type==

Mature B cell neoplasm

==Cancer Sub-Classification / Subtype==

Large B-cell lymphomas

==Definition / Description of Disease==

Diffuse, monomorphic neoplasm of large B-cells with a plasmablastic immunophenotype and ALK expression due to ''ALK'' rearrangement

==Synonyms / Terminology==

Not recommended: ALK-positive plasmablastic B-cell lymphoma; ALK-positive diffuse large B-cell lymphoma

==Epidemiology / Prevalence==

*<1% of large B-cell lymphomas
**~ 200 cases reported in literature to date<ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>

*Range: 9-85 years; median: ~ 40 years<ref>{{Cite journal|last=Pan|first=Zenggang|last2=Hu|first2=Shimin|last3=Li|first3=Min|last4=Zhou|first4=Yi|last5=Kim|first5=Young S.|last6=Reddy|first6=Vishnu|last7=Sanmann|first7=Jennifer N.|last8=Smith|first8=Lynette M.|last9=Chen|first9=Mingyi|date=2017-01|title=ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature|url=https://pubmed.ncbi.nlm.nih.gov/27740969|journal=The American Journal of Surgical Pathology|volume=41|issue=1|pages=25–38|doi=10.1097/PAS.0000000000000753|issn=1532-0979|pmid=27740969}}</ref><ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>
*Male to Female ratio: 3-4:1<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><ref>{{Cite journal|last=Castillo|first=Jorge J.|last2=Beltran|first2=Brady E.|last3=Malpica|first3=Luis|last4=Marques-Piubelli|first4=Mario L.|last5=Miranda|first5=Roberto N.|date=2021-12|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK + LBCL): a systematic review of clinicopathological features and management|url=https://pubmed.ncbi.nlm.nih.gov/34151703|journal=Leukemia & Lymphoma|volume=62|issue=12|pages=2845–2853|doi=10.1080/10428194.2021.1941929|issn=1029-2403|pmid=34151703}}</ref>

==Clinical Features==
{| class="wikitable"
|'''Signs and Symptoms'''
|Asymptomatic lymphadenopathy

B-symptoms
|-
|'''Laboratory Findings'''
|Serum LDH elevation
|}

==Sites of Involvement==

*Lymph nodes are most commonly involved (~ 75%)
*Extranodal sites: bone marrow, GI tract, liver, epidural space, ovaries, skeletal system, nasopharyngeal/nasal area, tongue, and brain<ref>{{Cite journal|last=Morgan|first=Elizabeth A.|last2=Nascimento|first2=Alessandra F.|date=2012|title=Anaplastic lymphoma kinase-positive large B-cell lymphoma: an underrecognized aggressive lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22474449|journal=Advances in Hematology|volume=2012|pages=529572|doi=10.1155/2012/529572|issn=1687-9112|pmc=3299366|pmid=22474449}}</ref><ref>{{Cite journal|last=Pan|first=Zenggang|last2=Hu|first2=Shimin|last3=Li|first3=Min|last4=Zhou|first4=Yi|last5=Kim|first5=Young S.|last6=Reddy|first6=Vishnu|last7=Sanmann|first7=Jennifer N.|last8=Smith|first8=Lynette M.|last9=Chen|first9=Mingyi|date=2017-01|title=ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature|url=https://pubmed.ncbi.nlm.nih.gov/27740969|journal=The American Journal of Surgical Pathology|volume=41|issue=1|pages=25–38|doi=10.1097/PAS.0000000000000753|issn=1532-0979|pmid=27740969}}</ref><ref>{{Cite journal|last=Laurent|first=Camille|last2=Do|first2=Catherine|last3=Gascoyne|first3=Randy D.|last4=Lamant|first4=Laurence|last5=Ysebaert|first5=Loïc|last6=Laurent|first6=Guy|last7=Delsol|first7=Georges|last8=Brousset|first8=Pierre|date=2009-09-01|title=Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis|url=https://pubmed.ncbi.nlm.nih.gov/19636007|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=27|issue=25|pages=4211–4216|doi=10.1200/JCO.2008.21.5020|issn=1527-7755|pmid=19636007}}</ref>

==Morphologic Features==

*Partial or diffuse effacement of lymph node architecture
*Lymphoma cells infiltrate sinusoids<ref>{{Cite journal|last=Pan|first=Zenggang|last2=Hu|first2=Shimin|last3=Li|first3=Min|last4=Zhou|first4=Yi|last5=Kim|first5=Young S.|last6=Reddy|first6=Vishnu|last7=Sanmann|first7=Jennifer N.|last8=Smith|first8=Lynette M.|last9=Chen|first9=Mingyi|date=2017-01|title=ALK-positive Large B-cell Lymphoma: A Clinicopathologic Study of 26 Cases With Review of Additional 108 Cases in the Literature|url=https://pubmed.ncbi.nlm.nih.gov/27740969|journal=The American Journal of Surgical Pathology|volume=41|issue=1|pages=25–38|doi=10.1097/PAS.0000000000000753|issn=1532-0979|pmid=27740969}}</ref><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>
*Monomorphic infiltrate of large cells with abundant amphophilic or eosinophilic cytoplasm

==Immunophenotype==

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||ALK, CD138, VS38, IRF4/MUM1, BLIMP1, XBP1
|-
|Positive (subset)||EMA (90%), Cytoplasmic Ig (90%), IgA (80%), CD45 (90%), CD30 (15%), CD4 (50%), CD57 (10%), CD43, Cytokeratin (10%)
|-
|Negative (universal)||Pan-T cell antigens, CD8, B-cell antigens, CD10, BCL-6, Cyclin-D1, HHV8
|}

==Chromosomal Rearrangements (Gene Fusions)==

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)
!ALK Immunostain Pattern!!Prevalence
!Notes
|-
|t(2;17)(p23;q23)||CLTC::ALK
|Cytoplasmic; granular||Most common
|<ref>{{Cite journal|last=Gascoyne|first=Randy D.|last2=Lamant|first2=Laurence|last3=Martin-Subero|first3=Jose I.|last4=Lestou|first4=Valia S.|last5=Harris|first5=Nancy Lee|last6=Müller-Hermelink|first6=Hans-Konrad|last7=Seymour|first7=John F.|last8=Campbell|first8=Lynda J.|last9=Horsman|first9=Douglas E.|date=2003-10-01|title=ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases|url=https://pubmed.ncbi.nlm.nih.gov/12763927|journal=Blood|volume=102|issue=7|pages=2568–2573|doi=10.1182/blood-2003-03-0786|issn=0006-4971|pmid=12763927}}</ref>
|-
|t(2;5)(p23;q35)
|NPM::ALK
|Nuclear and cytoplasmic
|
|<ref>{{Cite journal|last=Onciu|first=Mihaela|last2=Behm|first2=Frederick G.|last3=Downing|first3=James R.|last4=Shurtleff|first4=Sheila A.|last5=Raimondi|first5=Susana C.|last6=Ma|first6=Zhigui|last7=Morris|first7=Stephan W.|last8=Kennedy|first8=Wren|last9=Jones|first9=Sandra C.|date=2003-10-01|title=ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases|url=https://pubmed.ncbi.nlm.nih.gov/12816858|journal=Blood|volume=102|issue=7|pages=2642–2644|doi=10.1182/blood-2003-04-1095|issn=0006-4971|pmid=12816858}}</ref>
|-
|t(2;5)(p23;q35.3)
|SQSTM1::ALK
|Cytoplasmic; diffuse
|
|<ref>{{Cite journal|last=Takeuchi|first=Kengo|last2=Soda|first2=Manabu|last3=Togashi|first3=Yuki|last4=Ota|first4=Yasunori|last5=Sekiguchi|first5=Yasunobu|last6=Hatano|first6=Satoko|last7=Asaka|first7=Reimi|last8=Noguchi|first8=Masaaki|last9=Mano|first9=Hiroyuki|date=2011-03|title=Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21134980|journal=Haematologica|volume=96|issue=3|pages=464–467|doi=10.3324/haematol.2010.033514|issn=1592-8721|pmc=3046280|pmid=21134980}}</ref>
|-
|inv(2)(p23q13) or t(2;2)(p23;q13)
|RANBP2::ALK
|Nuclear membrane and perinuclear punctate
|
|<ref>{{Cite journal|last=Lee|first=Seung Eun|last2=Kang|first2=So Young|last3=Takeuchi|first3=Kengo|last4=Ko|first4=Young Hyeh|date=2014-12|title=Identification of RANBP2-ALK fusion in ALK positive diffuse large B-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24470379|journal=Hematological Oncology|volume=32|issue=4|pages=221–224|doi=10.1002/hon.2125|issn=1099-1069|pmid=24470379}}</ref>
|-
|inv(2)(p21p23)
|EML4::ALK
|Cytoplasmic; diffuse
|
|<ref>{{Cite journal|last=Sakamoto|first=Kana|last2=Nakasone|first2=Hideki|last3=Togashi|first3=Yuki|last4=Sakata|first4=Seiji|last5=Tsuyama|first5=Naoko|last6=Baba|first6=Satoko|last7=Dobashi|first7=Akito|last8=Asaka|first8=Reimi|last9=Tsai|first9=Chien-Chen|date=2016-04|title=ALK-positive large B-cell lymphoma: identification of EML4-ALK and a review of the literature focusing on the ALK immunohistochemical staining pattern|url=https://pubmed.ncbi.nlm.nih.gov/26781614|journal=International Journal of Hematology|volume=103|issue=4|pages=399–408|doi=10.1007/s12185-016-1934-1|issn=1865-3774|pmid=26781614}}</ref>
|-
|inv(2)(p21q31.1) or t(2;2)(p23;q31.1)
|GORASP2::ALK
|Cytoplasmic; diffuse
|
|<ref>{{Cite journal|last=Ise|first=Mikiko|last2=Kageyama|first2=Hajime|last3=Araki|first3=Akinobu|last4=Itami|first4=Makiko|date=2019-02|title=Identification of a novel GORASP2-ALK fusion in an ALK-positive large B-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30187817|journal=Leukemia & Lymphoma|volume=60|issue=2|pages=493–497|doi=10.1080/10428194.2018.1493731|issn=1029-2403|pmid=30187817}}</ref>
|-
|Cryptic
|SEC31A::ALK
|Cytoplasmic; granular
|
|<ref>{{Cite journal|last=Bedwell|first=Clare|last2=Rowe|first2=David|last3=Moulton|first3=Deborah|last4=Jones|first4=Gail|last5=Bown|first5=Nick|last6=Bacon|first6=Chris M.|date=2011-02|title=Cytogenetically complex SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/21109691|journal=Haematologica|volume=96|issue=2|pages=343–346|doi=10.3324/haematol.2010.031484|issn=1592-8721|pmc=3031708|pmid=21109691}}</ref>
|}

==Individual Region Genomic Gain/Loss/LOH==

Gains or amplifications of ''MYC'' (~50% of cases)<ref>{{Cite journal|last=Valera|first=Alexandra|last2=Colomo|first2=Lluis|last3=Martínez|first3=Antonio|last4=de Jong|first4=Daphne|last5=Balagué|first5=Olga|last6=Matheu|first6=Gabriel|last7=Martínez|first7=Mónica|last8=Taddesse-Heath|first8=Lekidelu|last9=Jaffe|first9=Elaine S.|date=2013-10|title=ALK-positive large B-cell lymphomas express a terminal B-cell differentiation program and activated STAT3 but lack MYC rearrangements|url=https://pubmed.ncbi.nlm.nih.gov/23599149|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=26|issue=10|pages=1329–1337|doi=10.1038/modpathol.2013.73|issn=1530-0285|pmc=6368829|pmid=23599149}}</ref>
==Characteristic Chromosomal Patterns==
N/A

==Gene Mutations (SNV/INDEL)==
N/A

==Epigenomic Alterations==
N/A

==Genes and Main Pathways Involved==
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|ALK rearrangement; Activating fusions
|JAK/STAT, PI3K/AKT, MAPK/ERK and phospholipase C gamma 2 (PLCG2) pathways
|Transformation, increased growth and inhibition of apoptosis
|}
==Genetic Diagnostic Testing Methods==

*Detection of ''ALK'' rearrangement by NGS or FISH
*Monoclonal ''IGH'' rearrangements by PCR

==Familial Forms==

N/A

==Additional Information==

N/A

==Links==

N/A

==References==
<references />
==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:ALK-Positive Large B-cell Lymphoma - Revision history

Bailey.Glen at 18:54, 3 November 2023

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Manando Nakasaki, MD, PhD (University of California, Irvine) Fabiola Quintero-Rivera, MD, FACMG (University of California, Irvi..."