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 (5th ed.)]]
 
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]


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


<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-30. 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: [[Nodular Sclerosis Classic Hodgkin Lymphoma]]
Other relevent pages include: [[HAEM4:Nodular Sclerosis Classic Hodgkin Lymphoma]]


Note: author needs to merge Nodular Sclerosis Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma, Mixed Cellularity Classic Hodgkin Lymphoma, Lymphocyte-Depleted Classic Hodgkin Lymphoma
Note: author needs to merge Nodular Sclerosis Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma, Mixed Cellularity Classic Hodgkin Lymphoma, Lymphocyte-Depleted Classic Hodgkin Lymphoma
}}</blockquote>
}}</blockquote>
==Primary Author(s)*==


Patricia V. Hernandez, M.D., Washington University School of Medicine
<span style="color:#0070C0">(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ <u>HGVS-based nomenclature for variants</u>], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>].)</span>


__TOC__
==Primary Author(s)*==


==Cancer Category / Type==
Xiaolin Hu, Ph.D., GeneDx
==WHO Classification of Disease==


Hodgkin's lymphoma
{| class="wikitable"
 
!Structure
==Cancer Sub-Classification / Subtype==
!Disease
 
|-
N/A
|Book
 
|Haematolymphoid Tumours (5th ed.)
==Definition / Description of Disease==
|-
 
|Category
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" />.
|B-cell lymphoid proliferations and lymphomas
 
|-
==Synonyms / Terminology==
|Family
|Hodgkin lymphoma
|-
|Type
|N/A
|-
|Subtype(s)
|Classic Hodgkin lymphoma
|}


N/A
==Related Terminology==


==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"
{| class="wikitable"
|'''Signs and Symptoms'''
|+
|Older in age
|Acceptable
Presentation at early stages are common
|N/A
 
Infrequent B symptoms (weight loss, fever, night sweats)
 
Infrequent mediastinal involvement and bulky disease
 
Usually good prognosis
|-
|-
|'''Laboratory Findings'''
|Not Recommended
|There is no characteristic finding in this condition. It can present with anemia, lymphocytopenia as a common condition of Hodgkin's lymphoma
|Hodgkin disease
|}
|}


==Sites of Involvement==
==Gene Rearrangements==
 
No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.
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"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!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
|-
|-
|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" />
|
|
|}
|}
==Chromosomal Rearrangements (Gene Fusions)==


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)
|-
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
|6q
EXAMPLE 30% (add reference)
|Loss
|Yes
|6q23-24
|TNFAIP3
|P
|No
|No
|Yes
|Loss of TNFAIP3 (A20) disrupts NF-κB regulation (PMID: 19380639)
|EXAMPLE
|}
 
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.  
Line 112: Line 123:
!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 175: Line 186:
|
|
|}
|}
==Characteristic Chromosomal 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 187: Line 233:
!Notes
!Notes
|-
|-
|EXAMPLE
|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
|Loss of MHC class I expression aids immune evasion (PMID: 21368758)
|-
|CIITA
|Inactivating mutations
|Tumor Suppressor Gene
|Rare (<5%)
|P
|No
|No
|Loss of MHC class II expression aids immune evasion (PMID: 21368758)
|-
|XPO1
|Missense mutations
|Oncogene
|Rare (<5%)
|Unknown
|No
|No
|EXAMPLE:
|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.
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
==Gene Mutations (SNV / INDEL)==


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 203: 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)
!Notes
!Notes
|-
|-
|EXAMPLE: TP53; Variable LOF mutations
|<span class="blue-text">EXAMPLE:</span> TP53; Variable LOF mutations


EXAMPLE:
<span class="blue-text">EXAMPLE:</span>


EGFR; Exon 20 mutations
EGFR; Exon 20 mutations


EXAMPLE: BRAF; Activating mutations
<span class="blue-text">EXAMPLE:</span> BRAF; Activating mutations
|EXAMPLE: TSG
|<span class="blue-text">EXAMPLE:</span> TSG
|EXAMPLE: 20% (COSMIC)
|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)


EXAMPLE: 30% (add Reference)
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
|EXAMPLE: IDH1 R123H
|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
|EXAMPLE: EGFR amplification
|<span class="blue-text">EXAMPLE:</span> EGFR amplification
|
|
|
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
|<span class="blue-text">EXAMPLE:</span> Excludes hairy cell leukemia (HCL) (add reference).
<br />
<br />
|}
|}
Line 232: 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 241: Line 341:
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|REL, TNFAIP3, NFKBIA, MAP3K14
|EXAMPLE: MAPK signaling
|NF-κB signaling
|EXAMPLE: Increased cell growth and proliferation
|Constitutive activation of classical and alternative NF-κB pathways promotes HRS cell survival (PMID: 19380639, 33686198)
|-
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|JAK2, STAT6, SOCS1
|EXAMPLE: Cell cycle regulation
|JAK/STAT signaling
|EXAMPLE: Unregulated cell division
|Dysregulation leads to proliferation and survival of HRS cells (PMID: 24531327, 29650799)
|-
|-
|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
|CD274 (PD-L1), PDCD1LG2 (PD-L2), B2M
|EXAMPLE:  Histone modification, chromatin remodeling
|Immune evasion
|EXAMPLE: Abnormal gene expression program
|Upregulation of PD-L1/PD-L2 and loss of MHC I/II expression enables immune escape (PMID: 20628145, 21368758)
|-
|-
|''REL'' (2p16), ''RELB'' (19q13), ''CD40'' (20q13) and ''MAP3K14'' (17q21)
|EBV LMP1, LMP2A
|nuclear factor (NF)-κB signalling
|Viral oncogenesis
|LMP1 mimics CD40 signaling, LMP2A mimics BCR signaling to promote HRS cell survival in EBV+ CHL (PMID: 9501091, 17682125)
|-
|
|
|
|-
|''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==
Line 275: Line 378:
==Links==
==Links==


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==References==
==References==
<references />
<references />
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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]]

Latest revision as of 08:19, 12 July 2025


Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent 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

Note: author needs to merge Nodular Sclerosis Classic Hodgkin Lymphoma, Lymphocyte-Rich Classic Hodgkin Lymphoma, Mixed Cellularity Classic Hodgkin Lymphoma, Lymphocyte-Depleted Classic Hodgkin Lymphoma

(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)

Primary Author(s)*

Xiaolin Hu, Ph.D., GeneDx

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Hodgkin lymphoma
Type N/A
Subtype(s) Classic Hodgkin lymphoma

Related Terminology

Acceptable N/A
Not Recommended Hodgkin disease

Gene Rearrangements

No characteristic chromosomal rearrangements have been reported for lymphocyte-rich classical Hodgkin's lymphoma.

Driver Gene Fusion(s) and Common Partner Genes Molecular Pathogenesis Typical Chromosomal Alteration(s) 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

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 (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.)

Chr # Gain, Loss, Amp, LOH Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] Relevant Gene(s) Diagnostic, Prognostic, and Therapeutic Significance - D, P, T Established Clinical Significance Per Guidelines - Yes or No (Source) Clinical Relevance Details/Other 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)
6q Loss 6q23-24 TNFAIP3 P No Loss of TNFAIP3 (A20) disrupts NF-κB regulation (PMID: 19380639)

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.

Chr # Gain / Loss / Amp / LOH Minimal Region Genomic Coordinates [Genome Build] Minimal Region Cytoband Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
2p [1][2] Gain chr2 Unknown Unknown Unknown It can result in REL (2p16), CD40 (20q13) [1]
9p [1][2] Gain chr9 Unknown Unknown Unknown It can result in JAK2, CD274 (PDL1) and PDCD1LG2 (PDL2) mutations. The amplification of 9p24.1 is critical to CD274/PDCD1LG2 gain of function[1]
17q [1][2] Gain chr17 Unknown Unknown Unknown it can result in MAP3K14 (17q21) mutation[1]
19q [1][2] Gain chr19 Unknown Unknown Unknown It can result in RELB (19q13) mutation[1]
20q [1][2] Gain chr20 Unknown Unknown Unknown CD40 is the lesion of 20q13[1]
6q [1][2] Loss chr6 Unknown Unknown Unknown
13q [1][2] Loss chr13 Unknown Unknown Unknown

Characteristic Chromosomal or Other Global Mutational Patterns

Put your text here and fill in the table (Instructions: 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.)

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
EXAMPLE:

Co-deletion of 1p and 18q

EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). EXAMPLE: Common (Oligodendroglioma) EXAMPLE: D, P
EXAMPLE:

Microsatellite instability - hypermutated

EXAMPLE: Common (Endometrial carcinoma) EXAMPLE: P, T

No characteristic chromosomal patterns have been reported for lymphocyte-rich classical Hodgkin's lymphoma.

Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
Aneuploidy, hypertetraploidy No unkonwn unknown Common in HRS cells; contributes to genomic instability (PMID: 7632954)

Gene Mutations (SNV/INDEL)

Put your text here and fill in the table (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.)

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 Loss of MHC class I expression aids immune evasion (PMID: 21368758)
CIITA Inactivating mutations Tumor Suppressor Gene Rare (<5%) P No Loss of MHC class II expression aids immune evasion (PMID: 21368758)
XPO1 Missense mutations 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 cBioportal, COSMIC, 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.

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) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

EGFR; Exon 20 mutations

EXAMPLE: BRAF; Activating mutations

EXAMPLE: TSG EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add Reference)

EXAMPLE: IDH1 R123H EXAMPLE: EGFR amplification EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).


Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

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

N/A

Gene; Genetic Alteration Pathway Pathophysiologic Outcome
REL, TNFAIP3, NFKBIA, MAP3K14 NF-κB signaling 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)
CD274 (PD-L1), PDCD1LG2 (PD-L2), B2M Immune evasion Upregulation of PD-L1/PD-L2 and loss of MHC I/II expression enables immune escape (PMID: 20628145, 21368758)
EBV LMP1, LMP2A Viral oncogenesis LMP1 mimics CD40 signaling, LMP2A mimics BCR signaling to promote HRS cell survival in EBV+ CHL (PMID: 9501091, 17682125)

Genetic Diagnostic Testing Methods

  • 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 aggregation and monozygotic twin concordance suggest genetic predisposition (PMID: 26311361, 34208754)

Additional Information

N/A

Links

Put a link here or anywhere appropriate in this page (Instructions: Highlight the text to which you want to add a link in this section or elsewhere, select the "Link" icon at the top of the wiki page, and search the name of the internal page to which you want to link this text, or enter an external internet address by including the "http://www." portion.)

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Wang, Hao-Wei; et al. (2019-01). "Diagnosis of Hodgkin lymphoma in the modern era". British Journal of Haematology. 184 (1): 45–59. doi:10.1111/bjh.15614. ISSN 1365-2141. PMC 6310079. PMID 30407610. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Steidl, Christian; et al. (2010-07-22). "Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome". Blood. 116 (3): 418–427. doi:10.1182/blood-2009-12-257345. ISSN 1528-0020. PMID 20339089.

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Notes

*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.


*Citation of this Page: “Classic Hodgkin lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 07/12/2025, https://ccga.io/index.php/HAEM5:Classic_Hodgkin_lymphoma.

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