Difference between revisions of "HAEM5:KSHV/HHV8-associated multicentric Castleman disease"

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(Created page with "{{DISPLAYTITLE:KSHV/HHV8-associated multicentric Castleman disease}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote class='...")
 
 
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{{DISPLAYTITLE:KSHV/HHV8-associated multicentric Castleman disease}}
 
{{DISPLAYTITLE:KSHV/HHV8-associated multicentric Castleman disease}}
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
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[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]
  
 
{{Under Construction}}
 
{{Under Construction}}
  
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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Multicentric Castleman Disease]].
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<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:Multicentric Castleman Disease]].
 
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<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>
 +
 
==Primary Author(s)*==
 
==Primary Author(s)*==
  
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__TOC__
 
__TOC__
  
−
==Cancer Category/Type==
+
==WHO Classification of Disease==
  
−
Multicentric Castleman Disease
+
{| class="wikitable"
−
 
+
!Structure
−
==Cancer Sub-Classification / Subtype==
+
!Disease
−
 
+
|-
−
Put your text here
+
|Book
 +
|Haematolymphoid Tumours (5th ed.)
 +
|-
 +
|Category
 +
|B-cell lymphoid proliferations and lymphomas
 +
|-
 +
|Family
 +
|Tumour like lesions with B-cell predominance
 +
|-
 +
|Type
 +
|N/A
 +
|-
 +
|Subtype(s)
 +
|KSHV/HHV8-associated multicentric Castleman disease
 +
|}
  
 
==Definition / Description of Disease==
 
==Definition / Description of Disease==
  
−
Put your text here <span style="color:#0070C0">(''Instructions: Brief description of approximately one paragraph - include disease context relative to other WHO classification categories referring to the specific WHO book pages, diagnostic criteria if applicable, and differential diagnosis if applicable'') </span>
+
Castleman disease was initially described in 1956 by Castleman ''et al'', who reported on 13 cases of localized mediastinal lymphoid proliferations in asymptomatic patients.<ref>{{Cite journal|last=Castleman|first=Benjamin|last2=Iverson|first2=Lalla|last3=Menendez|first3=V. Pardo|date=1956-07|title=Localized mediastinal lymph-node hyperplasia resembling thymoma|url=http://dx.doi.org/10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4|journal=Cancer|volume=9|issue=4|pages=822–830|doi=10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4|issn=0008-543X}}</ref> It is now recognized that there are different morphologic variants (hyaline vascular, plasma cell/plasmablastic, and mixed or transitional) as well as clinical forms (unicentric and multicentric) classified under the broad clinicopathologic syndrome termed Castleman disease.<ref name=":0">{{Cite journal|last=Chadburn|first=Amy|last2=Said|first2=Jonathan|last3=Gratzinger|first3=Dita|last4=Chan|first4=John K. C.|last5=de Jong|first5=Daphne|last6=Jaffe|first6=Elaine S.|last7=Natkunam|first7=Yasodha|last8=Goodlad|first8=John R.|date=2017-02|title=HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms|url=https://academic.oup.com/ajcp/article-lookup/doi/10.1093/ajcp/aqw218|journal=American Journal of Clinical Pathology|language=en|volume=147|issue=2|pages=171–187|doi=10.1093/ajcp/aqw218|issn=0002-9173}}</ref> Multicentric Castleman Disease is a rare clinicopathologic entity encompassing a group of systemic polyclonal lymphoproliferative disorders. It belongs to the spectrum of HHV8-associated lymphoproliferative disorders in which there is a proliferation of morphologically benign lymphocytes, plasma cells, and vessels due to excessive production of cytokines, IL6 features prominently amongst these.<ref name=":1">{{Cite journal|last=Swerdlow|first=Steven H.|last2=Campo|first2=Elias|last3=Pileri|first3=Stefano A.|last4=Harris|first4=Nancy Lee|last5=Stein|first5=Harald|last6=Siebert|first6=Reiner|last7=Advani|first7=Ranjana|last8=Ghielmini|first8=Michele|last9=Salles|first9=Gilles A.|date=2016-05-19|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=http://dx.doi.org/10.1182/blood-2016-01-643569|journal=Blood|volume=127|issue=20|pages=2375–2390|doi=10.1182/blood-2016-01-643569|issn=0006-4971}}</ref>Multicentric Castleman disease is idiopathic in HIV-negative and HHV8-negative patients.
  
 
==Synonyms / Terminology==
 
==Synonyms / Terminology==
  
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Put your text here <span style="color:#0070C0">(''Instructions: Include currently used terms and major historical ones, adding “(historical)” after the latter.'') </span>
+
Angio follicular lymph-node hyperplasia
 +
 
 +
Giant node hyperplasia
  
 
==Epidemiology / Prevalence==
 
==Epidemiology / Prevalence==
  
−
Put your text here
+
HHV8 Positive Multicentric Castleman Disease occurs in immunosuppressed patients across all ethnic groups, particularly in association with HIV/AIDS. <ref name=":1" /> Immunocompetent individuals may be affected with the disease in HHV8 endemic areas such as sub-Saharan Africa and Mediterranean countries. In cases where HIV was acquired via sexual transmission, there is a strong association with the development of HHV8-positive MCD, men are predominantly affected.
  
 
==Clinical Features==
 
==Clinical Features==
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
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|<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)
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EXAMPLE 30% (add reference)
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<span class="blue-text">EXAMPLE:</span> 30% (add reference)
 
|Yes
 
|Yes
 
|No
 
|No
 
|Yes
 
|Yes
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|EXAMPLE
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|<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).
 
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).
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No known recurrent abnormalities  
 
No known recurrent abnormalities  
 
</blockquote>
 
</blockquote>
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==Individual Region Genomic Gain/Loss/LOH==
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==Individual Region Genomic Gain / Loss / LOH==
  
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
7
 
7
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|EXAMPLE Loss
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|<span class="blue-text">EXAMPLE:</span> Loss
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr7:1- 159,335,973 [hg38]
 
chr7:1- 159,335,973 [hg38]
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chr7
 
chr7
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|Yes
 
|Yes
 
|No
 
|No
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
 
|-
 
|-
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
8
 
8
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|EXAMPLE Gain
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|<span class="blue-text">EXAMPLE:</span> Gain
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr8:1-145,138,636 [hg38]
 
chr8:1-145,138,636 [hg38]
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|<span class="blue-text">EXAMPLE:</span>
  
 
chr8
 
chr8
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|No
 
|No
 
|No
 
|No
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
Common recurrent secondary finding for t(8;21) (add reference).
 
Common recurrent secondary finding for t(8;21) (add reference).
 
|}
 
|}
  
−
<blockquote class='blockedit'>{{Box-round|title=v4:Individual Region Genomic Gain/Loss/LOH|The content below was from the previous version of the page. Please incorporate above.}}
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<blockquote class='blockedit'>{{Box-round|title=v4:Individual Region Genomic Gain / Loss / LOH|The content below was from the previous version of the page. Please incorporate above.}}
  
 
No known recurrent abnormalities  
 
No known recurrent abnormalities  
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==Characteristic Chromosomal Patterns==
 
==Characteristic Chromosomal Patterns==
  
−
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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'')</span>
+
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: 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. Do not delete table.'')</span>
  
 
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE
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|<span class="blue-text">EXAMPLE:</span>
  
 
Co-deletion of 1p and 18q
 
Co-deletion of 1p and 18q
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|No
 
|No
 
|No
 
|No
−
|EXAMPLE:
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|<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).
 
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
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No known recurrent abnormalities  
 
No known recurrent abnormalities  
 
</blockquote>
 
</blockquote>
−
==Gene Mutations (SNV/INDEL)==
+
==Gene Mutations (SNV / INDEL)==
  
−
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 and common as well either disease defining and/or clinically significant. Can include references 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.'') </span>
+
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 and common as well as either disease defining and/or clinically significant. Can include references 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. Do not delete table.'') </span>
  
 
{| class="wikitable sortable"
 
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!Notes
 
!Notes
 
|-
 
|-
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|EXAMPLE: TP53; Variable LOF mutations
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|<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)
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|<span class="blue-text">EXAMPLE:</span> 20% (COSMIC)
  
−
EXAMPLE: 30% (add Reference)
+
<span class="blue-text">EXAMPLE:</span> 30% (add Reference)
−
|EXAMPLE: IDH1 R123H
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|<span class="blue-text">EXAMPLE:</span> IDH1 R123H
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|EXAMPLE: EGFR amplification
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|<span class="blue-text">EXAMPLE:</span> EGFR amplification
 
|
 
|
 
|
 
|
 
|
 
|
−
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
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|<span class="blue-text">EXAMPLE:</span>  Excludes hairy cell leukemia (HCL) (add reference).
 
<br />
 
<br />
 
|}
 
|}
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<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the previous version of the page. Please incorporate above.}}
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<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV / INDEL)|The content below was from the previous version of the page. Please incorporate above.}}
  
 
No known recurrent abnormalities  
 
No known recurrent abnormalities  
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==Genes and Main Pathways Involved==
 
==Genes and Main Pathways Involved==
  
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
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Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table. Do not delete table.'')</span>
 
{| class="wikitable sortable"
 
{| class="wikitable sortable"
 
|-
 
|-
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
 
|-
 
|-
−
|EXAMPLE: BRAF and MAP2K1; Activating mutations
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|<span class="blue-text">EXAMPLE:</span> BRAF and MAP2K1; Activating mutations
−
|EXAMPLE: MAPK signaling
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|<span class="blue-text">EXAMPLE:</span> MAPK signaling
−
|EXAMPLE: Increased cell growth and proliferation
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|<span class="blue-text">EXAMPLE:</span> Increased cell growth and proliferation
 
|-
 
|-
−
|EXAMPLE: CDKN2A; Inactivating mutations
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|<span class="blue-text">EXAMPLE:</span> CDKN2A; Inactivating mutations
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|EXAMPLE: Cell cycle regulation
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|<span class="blue-text">EXAMPLE:</span> Cell cycle regulation
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|EXAMPLE: Unregulated cell division
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|<span class="blue-text">EXAMPLE:</span> Unregulated cell division
 
|-
 
|-
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|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations
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|<span class="blue-text">EXAMPLE:</span>  KMT2C and ARID1A; Inactivating mutations
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|EXAMPLE:  Histone modification, chromatin remodeling
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|<span class="blue-text">EXAMPLE:</span>  Histone modification, chromatin remodeling
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|EXAMPLE:  Abnormal gene expression program
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|<span class="blue-text">EXAMPLE:</span>  Abnormal gene expression program
 
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<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.
 
<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.
  
−
<nowiki>*</nowiki>''Citation of this Page'': “KSHV/HHV8-associated multicentric Castleman disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:KSHV/HHV8-associated_multicentric_Castleman_disease</nowiki>.==Other Sections==
+
<nowiki>*</nowiki>''Citation of this Page'': “KSHV/HHV8-associated multicentric Castleman disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:KSHV/HHV8-associated_multicentric_Castleman_disease</nowiki>.
−
Cancer Sub-Classification/Subtype
 
−
 
 
−
None
 
−
 
 
−
 
 
−
Definition/Description of Disease
 
−
 
 
−
 
 
−
Castleman disease was initially described in 1956 by Castleman ''et al'', who reported on 13 cases of localized mediastinal lymphoid proliferations in asymptomatic patients.<ref>{{Cite journal|last=Castleman|first=Benjamin|last2=Iverson|first2=Lalla|last3=Menendez|first3=V. Pardo|date=1956-07|title=Localized mediastinal lymph-node hyperplasia resembling thymoma|url=http://dx.doi.org/10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4|journal=Cancer|volume=9|issue=4|pages=822–830|doi=10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4|issn=0008-543X}}</ref> It is now recognized that there are different morphologic variants (hyaline vascular, plasma cell/plasmablastic, and mixed or transitional) as well as clinical forms (unicentric and multicentric) classified under the broad clinicopathologic syndrome termed Castleman disease.<ref name=":0">{{Cite journal|last=Chadburn|first=Amy|last2=Said|first2=Jonathan|last3=Gratzinger|first3=Dita|last4=Chan|first4=John K. C.|last5=de Jong|first5=Daphne|last6=Jaffe|first6=Elaine S.|last7=Natkunam|first7=Yasodha|last8=Goodlad|first8=John R.|date=2017-02|title=HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms|url=https://academic.oup.com/ajcp/article-lookup/doi/10.1093/ajcp/aqw218|journal=American Journal of Clinical Pathology|language=en|volume=147|issue=2|pages=171–187|doi=10.1093/ajcp/aqw218|issn=0002-9173}}</ref> Multicentric Castleman Disease is a rare clinicopathologic entity encompassing a group of systemic polyclonal lymphoproliferative disorders. It belongs to the spectrum of HHV8-associated lymphoproliferative disorders in which there is a proliferation of morphologically benign lymphocytes, plasma cells, and vessels due to excessive production of cytokines, IL6 features prominently amongst these.<ref name=":1">{{Cite journal|last=Swerdlow|first=Steven H.|last2=Campo|first2=Elias|last3=Pileri|first3=Stefano A.|last4=Harris|first4=Nancy Lee|last5=Stein|first5=Harald|last6=Siebert|first6=Reiner|last7=Advani|first7=Ranjana|last8=Ghielmini|first8=Michele|last9=Salles|first9=Gilles A.|date=2016-05-19|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=http://dx.doi.org/10.1182/blood-2016-01-643569|journal=Blood|volume=127|issue=20|pages=2375–2390|doi=10.1182/blood-2016-01-643569|issn=0006-4971}}</ref>Multicentric Castleman disease is idiopathic in HIV-negative and HHV8-negative patients.
 
−
 
 
−
 
 
−
Synonyms/Terminology
 
−
 
 
−
 
 
−
Angio follicular lymph-node hyperplasia
 
−
 
 
−
Giant node hyperplasia
 
−
 
 
−
 
 
−
Epidemiology/Prevalence
 
−
 
 
−
 
 
−
HHV8 Positive Multicentric Castleman Disease occurs in immunosuppressed patients across all ethnic groups, particularly in association with HIV/AIDS. <ref name=":1" /> Immunocompetent individuals may be affected with the disease in HHV8 endemic areas such as sub-Saharan Africa and Mediterranean countries. In cases where HIV was acquired via sexual transmission, there is a strong association with the development of HHV8-positive MCD, men are predominantly affected.
 
−
 
 
 
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases K]]
 
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases K]]

Latest revision as of 17:25, 6 September 2024

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:Multicentric Castleman Disease.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. 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 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 Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

Sudha Arumugam, MD

WHO Classification of Disease

Structure Disease
Book Haematolymphoid Tumours (5th ed.)
Category B-cell lymphoid proliferations and lymphomas
Family Tumour like lesions with B-cell predominance
Type N/A
Subtype(s) KSHV/HHV8-associated multicentric Castleman disease

Definition / Description of Disease

Castleman disease was initially described in 1956 by Castleman et al, who reported on 13 cases of localized mediastinal lymphoid proliferations in asymptomatic patients.[1] It is now recognized that there are different morphologic variants (hyaline vascular, plasma cell/plasmablastic, and mixed or transitional) as well as clinical forms (unicentric and multicentric) classified under the broad clinicopathologic syndrome termed Castleman disease.[2] Multicentric Castleman Disease is a rare clinicopathologic entity encompassing a group of systemic polyclonal lymphoproliferative disorders. It belongs to the spectrum of HHV8-associated lymphoproliferative disorders in which there is a proliferation of morphologically benign lymphocytes, plasma cells, and vessels due to excessive production of cytokines, IL6 features prominently amongst these.[3]Multicentric Castleman disease is idiopathic in HIV-negative and HHV8-negative patients.

Synonyms / Terminology

Angio follicular lymph-node hyperplasia

Giant node hyperplasia

Epidemiology / Prevalence

HHV8 Positive Multicentric Castleman Disease occurs in immunosuppressed patients across all ethnic groups, particularly in association with HIV/AIDS. [3] Immunocompetent individuals may be affected with the disease in HHV8 endemic areas such as sub-Saharan Africa and Mediterranean countries. In cases where HIV was acquired via sexual transmission, there is a strong association with the development of HHV8-positive MCD, men are predominantly affected.

Clinical Features


Signs and Symptoms Progressive lymphadenopathy

Splenomegaly or hepatosplenomegaly

Fever

Night sweats

Fatigue

Weight loss

Respiratory symptoms

Coincident Kaposi Sarcoma or HHV8-positive diffuse large B-cell lymphoma

Skin rash

Laboratory Findings Anemia

Thrombocytopenia

Hypoalbuminemia

Hypogammaglobinemia

Elevated C-reactive protein

Sites of Involvement

Multicentric Castleman Disease affects multiple lymph node sites, predominantly in the cervical region and commonly involves the spleen.[4]

Morphologic Features

HHV8-infected plasmablasts are the characteristic features of HHV8 Multicentric Castleman disease.[4] Plasmablasts are present in the lymph node and spleen.[2] The B cell follicles of lymph nodes shows varying degree of hyalinization and involution of germinal centers with prominent mantle zones that may intrude and efface the germinal centers.[3] Follicles may show onion skinning or widened concentric rings of mantle zone lymphocytes along with prominent penetrating venules, these findings are typical of Castleman disease.[3] Variable numbers of medium to large plasmablasts with amphophilic cytoplasm and eccentrically placed nuclei can be found among the mantle zone cells and adjacent interfollicular regions.[3] Sheets of mature plasma cells may be seen expanding the interfollicular region, some such cells may display cytoplasmic inclusions (Russell bodies) or crystalline forms.[3] With disease progression, the plasmablasts increase in number and may coalesce to form clusters.[3] If the disease proceeds to become HHV8-positive diffuse large B-cell lymphoma, NOS these clusters may expand clonally to form sheets of lymphoma cells that efface the normal follicular architecture.[3] Plasmablastic aggregates that develop during disease progression may be oligoclonal or monoclonal.

Immunophenotype

Finding Marker
Positive (universal) HHV 8 LANA 1, strong c IgM expression with lambda light chain restriction, CD20+/-, CD 79a -/+ [3]
Positive (subset) Viral IL-6 [3]
Negative (universal) CD 138, PAX 5, CD38-/+, CD27, EBV encoded small RNA [3]
Negative (subset) None

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE: t(9;22)(q34;q11.2) EXAMPLE: 3'ABL1 / 5'BCR EXAMPLE: der(22) EXAMPLE: 20% (COSMIC)

EXAMPLE: 30% (add reference)

Yes No Yes 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).


editv4:Chromosomal Rearrangements (Gene Fusions)
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No known recurrent abnormalities

Individual Region Genomic Gain / Loss / LOH

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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
EXAMPLE:

7

EXAMPLE: Loss EXAMPLE:

chr7:1- 159,335,973 [hg38]

EXAMPLE:

chr7

Yes Yes No EXAMPLE:

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

EXAMPLE:

8

EXAMPLE: Gain EXAMPLE:

chr8:1-145,138,636 [hg38]

EXAMPLE:

chr8

No No No EXAMPLE:

Common recurrent secondary finding for t(8;21) (add reference).

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No known recurrent abnormalities

Characteristic Chromosomal Patterns

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Chromosomal Pattern Diagnostic Significance (Yes, No or Unknown) Prognostic Significance (Yes, No or Unknown) Therapeutic Significance (Yes, No or Unknown) Notes
EXAMPLE:

Co-deletion of 1p and 18q

Yes No No EXAMPLE:

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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No known recurrent abnormalities

Gene Mutations (SNV / INDEL)

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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.


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No known recurrent abnormalities

Epigenomic Alterations

No known recurrent abnormalities

Genes and Main Pathways Involved

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Gene; Genetic Alteration Pathway Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations EXAMPLE: MAPK signaling EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations EXAMPLE: Cell cycle regulation EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations EXAMPLE:  Histone modification, chromatin remodeling EXAMPLE:  Abnormal gene expression program
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No known recurrent abnormalities

Genetic Diagnostic Testing Methods

No known recurrent abnormalities

Familial Forms

Given there are no recurrent genetic abnormalities associated with MCD, no method can be recommended at present.

Additional Information

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Links

None

References

  1. ↑ Castleman, Benjamin; et al. (1956-07). <822::aid-cncr2820090430>3.0.co;2-4 "Localized mediastinal lymph-node hyperplasia resembling thymoma". Cancer. 9 (4): 822–830. doi:10.1002/1097-0142(195607/08)9:4<822::aid-cncr2820090430>3.0.co;2-4. ISSN 0008-543X. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 Chadburn, Amy; et al. (2017-02). "HHV8/KSHV-Positive Lymphoproliferative Disorders and the Spectrum of Plasmablastic and Plasma Cell Neoplasms". American Journal of Clinical Pathology. 147 (2): 171–187. doi:10.1093/ajcp/aqw218. ISSN 0002-9173. Check date values in: |date= (help)
  3. ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Swerdlow, Steven H.; et al. (2016-05-19). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–2390. doi:10.1182/blood-2016-01-643569. ISSN 0006-4971.
  4. ↑ 4.0 4.1 Balakrishna J. Castleman disease. PathologyOutlines.com website.https://www.pathologyoutlines.com/topic/lymphnodescastleman.html. Accessed November 24th, 2021.

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: “KSHV/HHV8-associated multicentric Castleman disease”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:KSHV/HHV8-associated_multicentric_Castleman_disease.

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