Compendium of Cancer Genome Aberrations

HAEM5:Classic Hodgkin lymphoma: Difference between revisions

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{{DISPLAYTITLE:Classic Hodgkin lymphoma}}
{{DISPLAYTITLE:Classic Hodgkin lymphoma}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


{{Under Construction}}
{{Under Construction}}


<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Lymphocyte-Rich Classic Hodgkin Lymphoma]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Lymphocyte-Rich Classic Hodgkin Lymphoma]].
Other relevent pages include: [[HAEM4:Nodular Sclerosis Classic Hodgkin Lymphoma]]
Other relevent pages include: [[HAEM4:Nodular Sclerosis Classic Hodgkin Lymphoma]]


Line 14: Line 15:
==Primary Author(s)*==
==Primary Author(s)*==


Patricia V. Hernandez, M.D., Washington University School of Medicine
Xiaolin Hu, Ph.D., GeneDx
 
__TOC__
 
==WHO Classification of Disease==
==WHO Classification of Disease==


Line 40: Line 38:
|}
|}


==Definition / Description of Disease==
==Related Terminology==
 
Variant of classical Hodgkin's lymphoma rich in lymphocytes, with expanded mantle zones, atrophic germinal centers, small number of Reed-Stenberg cells and classical Hodgkin's lymphoma immonophenotype <ref name=":2">{{Cite journal|last=Nam-Cha|first=Syong H.|last2=Montes-Moreno|first2=Santiago|last3=Salcedo|first3=Maria T.|last4=Sanjuan|first4=Josefina|last5=Garcia|first5=Juan F.|last6=Piris|first6=Miguel A.|date=2009-08|title=Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers|url=https://pubmed.ncbi.nlm.nih.gov/19465900|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=22|issue=8|pages=1006–1015|doi=10.1038/modpathol.2009.54|issn=1530-0285|pmid=19465900}}</ref><ref name=":3" />.
 
==Synonyms / Terminology==
 
N/A
 
==Epidemiology / Prevalence==
 
It was the last subtype of classical Hodgkin lymphoma to be described and presents a low frequency, accounting for 3-5% of classical Hodgkin lymphomas <ref name=":1">{{Cite journal|last=Jiang|first=Manli|last2=Bennani|first2=N. Nora|last3=Feldman|first3=Andrew L.|date=2017-03|title=Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/28133975|journal=Expert Review of Hematology|volume=10|issue=3|pages=239–249|doi=10.1080/17474086.2017.1281122|issn=1747-4094|pmc=5514564|pmid=28133975}}</ref>. Because of its rarity, the literature is limited on this type of lymphoma.
 
==Clinical Features==
 
The main clinical features are listed below <ref name=":3">{{Cite journal|last=Diehl|first=V.|last2=Sextro|first2=M.|last3=Franklin|first3=J.|last4=Hansmann|first4=M. L.|last5=Harris|first5=N.|last6=Jaffe|first6=E.|last7=Poppema|first7=S.|last8=Harris|first8=M.|last9=Franssila|first9=K.|date=1999-03|title=Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease|url=https://pubmed.ncbi.nlm.nih.gov/10071266|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=17|issue=3|pages=776–783|doi=10.1200/JCO.1999.17.3.776|issn=0732-183X|pmid=10071266}}</ref><ref name=":0" /><ref>{{Cite journal|last=Shimabukuro-Vornhagen|first=Alexander|last2=Haverkamp|first2=Heinz|last3=Engert|first3=Andreas|last4=Balleisen|first4=Leopold|last5=Majunke|first5=Peter|last6=Heil|first6=Günther|last7=Eich|first7=Hans Theodor|last8=Stein|first8=Harald|last9=Diehl|first9=Volker|date=2005-08-20|title=Lymphocyte-rich classical Hodgkin's lymphoma: clinical presentation and treatment outcome in 100 patients treated within German Hodgkin's Study Group trials|url=https://pubmed.ncbi.nlm.nih.gov/16009944|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=23|issue=24|pages=5739–5745|doi=10.1200/JCO.2005.17.970|issn=0732-183X|pmid=16009944}}</ref>.
{| class="wikitable"
|'''Signs and Symptoms'''
|Older in age
Presentation at early stages are common
 
Infrequent B symptoms (weight loss, fever, night sweats)
 
Infrequent mediastinal involvement and bulky disease
 
Usually good prognosis
|-
|'''Laboratory Findings'''
|There is no characteristic finding in this condition. It can present with anemia, lymphocytopenia as a common condition of Hodgkin's lymphoma
|}


==Sites of Involvement==
Nodal disease with involvement of cervical lymph nodes. Mediastinal mass are rarely seen.
==Morphologic Features==
Lymphocyte-rich subtype presents intermediate characteristics between those of classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma <ref name=":2" /><ref name=":1" />. The main feature is the predominance of small-lymphocytes in the background resembling nodular sclerosis classical Hodgkin Lymphoma,<ref name=":4">{{Cite journal|last=Wang|first=Hao-Wei|last2=Balakrishna|first2=Jayalakshmi P.|last3=Pittaluga|first3=Stefania|last4=Jaffe|first4=Elaine S.|date=2019-01|title=Diagnosis of Hodgkin lymphoma in the modern era|url=https://pubmed.ncbi.nlm.nih.gov/30407610|journal=British Journal of Haematology|volume=184|issue=1|pages=45–59|doi=10.1111/bjh.15614|issn=1365-2141|pmc=6310079|pmid=30407610}}</ref> but with T-cell populations surrounding the germinal centers <ref name=":2" />. Classic Reed Sternberg cells are found adjacent to germinal centers in approximately 89.5% of cases although they account for only a small fraction of the cells <ref name=":0">{{Cite journal|last=Anagnostopoulos|first=I.|last2=Hansmann|first2=M. L.|last3=Franssila|first3=K.|last4=Harris|first4=M.|last5=Harris|first5=N. L.|last6=Jaffe|first6=E. S.|last7=Han|first7=J.|last8=van Krieken|first8=J. M.|last9=Poppema|first9=S.|date=2000-09-01|title=European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals 2 types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes|url=https://pubmed.ncbi.nlm.nih.gov/10961891|journal=Blood|volume=96|issue=5|pages=1889–1899|issn=0006-4971|pmid=10961891}}</ref>. There are three growth patterns, the most frequent is the nodular pattern, with intact or atrophic germinal centers composed of small lymphoid cells displaying round nuclei <ref name=":0" /> . Other growth patterns are interfollicular, composed of neoplastic cells forming small nodules with expansion to interfollicular areas and infiltration to adjacent mantle zones, and more rarely a diffuse growth pattern in which a germinal center is not seen <ref name=":0" />.
==Immunophenotype==
Immunophenotype of lymphoma-rich classical Hodgkin lymphoma is shown in the table below <ref name=":2" /><ref name=":0" />.
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD30 <ref name=":2" />, MUM-1 <ref name=":2" />, TRA-1 <ref name=":2" />
|-
|Positive (subset)||CD15 (56%) <ref name=":2" />, EBER (31%) <ref name=":2" />, CD20 (31%) <ref name=":2" />, CD79a (13%) <ref name=":0" />, OCT.1 (50%) <ref name=":2" />, OCT.2 (56%) <ref name=":2" />, BOB.1 (62%) <ref name=":2" />, Pax-5 (94%) <ref name=":2" />, KLHL6 (69%) <ref name=":2" />, P-50 (73%) <ref name=":2" />
|-
|Negative (universal)||GCET-1 <ref name=":2" />, J-chain <ref name=":0" />
|-
|Negative (subset)||CD20 (68%) <ref name=":0" />, EBER (53%) <ref name=":0" />, BCL6 (64%) <ref name=":2" />, C-REL (75%) <ref name=":2" />, REL-B (88%) <ref name=":2" />, IgD (94%) <ref name=":2" />, Blimp-1 (25%) <ref name=":2" />
|}
==WHO Essential and Desirable Genetic Diagnostic Criteria==
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
{| class="wikitable"
|+
|WHO Essential Criteria (Genetics)*
|
|-
|WHO Desirable Criteria (Genetics)*
|
|-
|Other Classification
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
{| class="wikitable"
|+
|+
|Acceptable
|Acceptable
|
|N/A
|-
|-
|Not Recommended
|Not Recommended
|
|Hodgkin disease
|}
|}


==Gene Rearrangements==
==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
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!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference).
|-
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|<span class="blue-text">EXAMPLE:</span> T
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|-
|-
|
|
Line 183: Line 71:
No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.
No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.


==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!Diagnostic Significance (Yes, No or Unknown)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Prognostic Significance (Yes, No or Unknown)
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Therapeutic Significance (Yes, No or Unknown)
!Clinical Relevance Details/Other Notes
!Notes
|-
|2p
|gain
|2p13
|REL
|P
|No
|REL amplification promotes NF-κB signaling activation (PMID: 19380639)
|-
|9p
|Gain
|9p24.1
|CD274 (PD-L1), PDCD1LG2 (PD-L2), JAK2
|T, P
|Yes (PMID:20628145)
|9p24.1 amplification drives PD-L1/PD-L2 overexpression, relevant for immune checkpoint inhibitor therapy (PMID: 20628145, 27069084)
|-
|17p
|Gain
|17q21
|MAP3K14
|P
|No
|MAP3K14 (NIK) gain activates alternative NF-κB signaling (PMID: 19380639)
|-
|-
|<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)||<span class="blue-text">EXAMPLE:</span> 3'ABL1 / 5'BCR||<span class="blue-text">EXAMPLE:</span> der(22)||<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
|6q
<span class="blue-text">EXAMPLE:</span> 30% (add reference)
|Loss
|Yes
|6q23-24
|TNFAIP3
|P
|No
|No
|Yes
|Loss of TNFAIP3 (A20) disrupts NF-κB regulation (PMID: 19380639)
|<span class="blue-text">EXAMPLE:</span>
 
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
|}
==Individual Region Genomic Gain/Loss/LOH==


There is no typical findings for lymphocyte-rich classical Hodgkin's lymphoma, the main features are also seen in other classical Hodgkin's lymphoma subtypes.  
There is no typical findings for lymphocyte-rich classical Hodgkin's lymphoma, the main features are also seen in other classical Hodgkin's lymphoma subtypes.  
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!Notes
!Notes
|-
|-
|2p <ref name=":4" /><ref name=":5">{{Cite journal|last=Steidl|first=Christian|last2=Telenius|first2=Adele|last3=Shah|first3=Sohrab P.|last4=Farinha|first4=Pedro|last5=Barclay|first5=Lorena|last6=Boyle|first6=Merrill|last7=Connors|first7=Joseph M.|last8=Horsman|first8=Douglas E.|last9=Gascoyne|first9=Randy D.|date=2010-07-22|title=Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome|url=https://pubmed.ncbi.nlm.nih.gov/20339089|journal=Blood|volume=116|issue=3|pages=418–427|doi=10.1182/blood-2009-12-257345|issn=1528-0020|pmid=20339089}}</ref>
|2p <ref name=":4">{{Cite journal|last=Wang|first=Hao-Wei|last2=Balakrishna|first2=Jayalakshmi P.|last3=Pittaluga|first3=Stefania|last4=Jaffe|first4=Elaine S.|date=2019-01|title=Diagnosis of Hodgkin lymphoma in the modern era|url=https://pubmed.ncbi.nlm.nih.gov/30407610|journal=British Journal of Haematology|volume=184|issue=1|pages=45–59|doi=10.1111/bjh.15614|issn=1365-2141|pmc=6310079|pmid=30407610}}</ref><ref name=":5">{{Cite journal|last=Steidl|first=Christian|last2=Telenius|first2=Adele|last3=Shah|first3=Sohrab P.|last4=Farinha|first4=Pedro|last5=Barclay|first5=Lorena|last6=Boyle|first6=Merrill|last7=Connors|first7=Joseph M.|last8=Horsman|first8=Douglas E.|last9=Gascoyne|first9=Randy D.|date=2010-07-22|title=Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome|url=https://pubmed.ncbi.nlm.nih.gov/20339089|journal=Blood|volume=116|issue=3|pages=418–427|doi=10.1182/blood-2009-12-257345|issn=1528-0020|pmid=20339089}}</ref>
|Gain
|Gain
|
|
Line 276: Line 186:
|
|
|}
|}
==Characteristic Chromosomal or Other Global Mutational Patterns==
==Characteristic Chromosomal or Other Global Mutational Patterns==
Put your text here and fill in the table <span style="color:#0070C0">(I''nstructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Molecular Pathogenesis
!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|<span class="blue-text">EXAMPLE:</span>
Co-deletion of 1p and 18q
|<span class="blue-text">EXAMPLE:</span> See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|<span class="blue-text">EXAMPLE:</span> Common (Oligodendroglioma)
|<span class="blue-text">EXAMPLE:</span> D, P
|
|
|-
|<span class="blue-text">EXAMPLE:</span>
Microsatellite instability - hypermutated
|
|<span class="blue-text">EXAMPLE:</span> Common (Endometrial carcinoma)
|<span class="blue-text">EXAMPLE:</span> P, T
|
|
|-
|
|
|
|
|
|
|}


No characteristic chromosomal patterns have been reported for lymphocyte-rich classical Hodgkin's lymphoma.
No characteristic chromosomal patterns have been reported for lymphocyte-rich classical Hodgkin's lymphoma.
Line 288: Line 233:
!Notes
!Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|Aneuploidy, hypertetraploidy
|No
|unkonwn
|unknown
|Common in HRS cells; contributes to genomic instability (PMID: 7632954)
|}


Co-deletion of 1p and 18q
==Gene Mutations (SNV/INDEL)==
|Yes
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
|-
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|TNFAIP3
|Inactivating mutation
|Tumor Suppressor Gene
|Recurrent (5-20%)
|P
|No
|Loss of function mutations disrupt NF-κB regulation (PMID: 19380639)
|-
|SOCS1
|Frameshift and nonsense mutations
|Tumor Suppressor Gene
|Recurrent (5-20%)
|P
|No
|SOCS1 mutations activate JAK/STAT signaling (PMID: 24531327)
|-
|STAT6
|Missense mutations
|Oncogene
|Recurrent (5-20%)
|P
|No
|STAT6 mutations drive cytokine signaling alterations (PMID: 24531327, 29650799)
|-
|B2M
|Inactivating mutations
|Tumor Suppressor Gene
|Rare (<5%)
|P
|No
|No
|Loss of MHC class I expression aids immune evasion (PMID: 21368758)
|-
|CIITA
|Inactivating mutations
|Tumor Suppressor Gene
|Rare (<5%)
|P
|No
|No
|<span class="blue-text">EXAMPLE:</span>
|Loss of MHC class II expression aids immune evasion (PMID: 21368758)
 
|-
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|XPO1
|}
|Missense mutations
==Gene Mutations (SNV/INDEL)==
|Oncogene
|Rare (<5%)
|Unknown
|No
|Emerging evidence of role in CHL pathogenesis (PMID: 33686198)
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


No characteristic gene mutations have been reported for lymphocyte-rich classical Hodgkin's lymphoma.  
No characteristic gene mutations have been reported for lymphocyte-rich classical Hodgkin's lymphoma.  
Line 304: Line 303:
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!Gene; Genetic Alteration!!Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)!!Prevalence (COSMIC /  TCGA / Other)!!Concomitant Mutations!!Mutually Exclusive Mutations
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
Line 333: Line 332:
==Epigenomic Alterations==
==Epigenomic Alterations==


N/A
Global downregulation of B-cell transcription factors (OCT2, BOB1, PU.1) and epigenetic silencing of B-cell program genes (PMID: 19465900, 14694522)


==Genes and Main Pathways Involved==
==Genes and Main Pathways Involved==
Line 342: Line 341:
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
|REL, TNFAIP3, NFKBIA, MAP3K14
|<span class="blue-text">EXAMPLE:</span> MAPK signaling
|NF-κB signaling
|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
|Constitutive activation of classical and alternative NF-κB pathways promotes HRS cell survival (PMID: 19380639, 33686198)
|-
|JAK2, STAT6, SOCS1
|JAK/STAT signaling
|Dysregulation leads to proliferation and survival of HRS cells (PMID: 24531327, 29650799)
|-
|-
|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
|CD274 (PD-L1), PDCD1LG2 (PD-L2), B2M
|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
|Immune evasion
|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
|Upregulation of PD-L1/PD-L2 and loss of MHC I/II expression enables immune escape (PMID: 20628145, 21368758)
|-
|-
|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
|EBV LMP1, LMP2A
|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
|Viral oncogenesis
|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
|LMP1 mimics CD40 signaling, LMP2A mimics BCR signaling to promote HRS cell survival in EBV+ CHL (PMID: 9501091, 17682125)
|-
|-
|''REL'' (2p16), ''RELB'' (19q13), ''CD40'' (20q13) and ''MAP3K14'' (17q21)
|nuclear factor (NF)-κB signalling
|
|
|-
|
|''JAK2'' amplification
|PD-L1 protein expression/ JAK/STAT pathway
|
|
|}
|}
==Genetic Diagnostic Testing Methods==
==Genetic Diagnostic Testing Methods==


N/A
*Immunohistochemistry for CD30, CD15, PAX5, and EBV (EBER in situ hybridization) (PMID: 2477085, 6946981)
*9p24.1 copy number assessment (FISH or NGS) may be used in refractory/relapsed cases to evaluate PD-L1/PD-L2 amplification for potential immunotherapy (PMID: 29394125).
*TR clonality assays can help exclude T-cell lymphomas in challenging differential diagnoses (PMID: 24128129).
*Targeted NGS panels for NF-κB and JAK/STAT pathway mutations (PMID: 33686198)


==Familial Forms==
==Familial Forms==


N/A
Familial aggregation and monozygotic twin concordance suggest genetic predisposition (PMID: 26311361, 34208754)


==Additional Information==
==Additional Information==
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<nowiki>*</nowiki>''Citation of this Page'': “Classic Hodgkin lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Classic_Hodgkin_lymphoma</nowiki>.
<nowiki>*</nowiki>''Citation of this Page'': “Classic Hodgkin lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Classic_Hodgkin_lymphoma</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]
[[Category:HAEM5]]
[[Category:DISEASE]]
[[Category:Diseases C]]
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