HAEM5:Classic Hodgkin lymphoma: Difference between revisions

<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]].

<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ 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 to a table, click within the table and select the > symbol that appears to be given options. 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>

Patricia V. Hernandez, M.D., Washington University School of Medicine

 

==Cancer Category / Type==

 

Hodgkin's lymphoma

 

==Cancer Sub-Classification / Subtype==

|'''Signs and Symptoms'''

|Older in age

Infrequent B symptoms (weight loss, fever, night sweats)

 

Infrequent mediastinal involvement and bulky disease

 

|'''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==

 

 

==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 of lymphoma-rich classical Hodgkin lymphoma is shown in the table below <ref name=":2" /><ref name=":0" />.

!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" />

|}

 

==Chromosomal Rearrangements (Gene Fusions)==

 

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

 

{| class="wikitable sortable"

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

|<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)

|Yes

|Yes

|<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).

 

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.

|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>

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

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

Co-deletion of 1p and 18q

|Yes

|<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).

|}

==Gene Mutations (SNV / INDEL)==

!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)'''

|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations

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

|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation

|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation

|<span class="blue-text">EXAMPLE:</span> Unregulated cell division

|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations

|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling

|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program

|''REL'' (2p16), ''RELB'' (19q13), ''CD40'' (20q13) and ''MAP3K14'' (17q21)

|nuclear factor (NF)-κB signalling

N/A

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases C]]