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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 (WHO Classification, 5th ed.)]] | | [[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]] |
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| {{Under Construction}} | | {{Under Construction}} |
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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]]. | | <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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| |Subtype(s) | | |Subtype(s) |
| |KSHV/HHV8-associated multicentric Castleman disease | | |KSHV/HHV8-associated multicentric Castleman disease |
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| ==Definition / Description of Disease==
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| 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.
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| ==Synonyms / Terminology==
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| Angio follicular lymph-node hyperplasia
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| Giant node hyperplasia
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| ==Epidemiology / Prevalence==
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| 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.
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| ==Clinical Features==
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| <br />
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| {| class="wikitable"
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| |'''Signs and Symptoms'''
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| |Progressive lymphadenopathy
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| Splenomegaly or hepatosplenomegaly
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| Fever
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| Night sweats
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| Fatigue
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| Weight loss
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| Respiratory symptoms
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| Coincident Kaposi Sarcoma or HHV8-positive diffuse large B-cell lymphoma
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| Skin rash
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| |-
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| |'''Laboratory Findings'''
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| |Anemia
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| Thrombocytopenia
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| Hypoalbuminemia
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| Hypogammaglobinemia
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| Elevated C-reactive protein
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| |}
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| ==Sites of Involvement==
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| Multicentric Castleman Disease affects multiple lymph node sites, predominantly in the cervical region and commonly involves the spleen.<ref name=":2">Balakrishna J. Castleman disease. PathologyOutlines.com website.<nowiki>https://www.pathologyoutlines.com/topic/lymphnodescastleman.html</nowiki>. Accessed November 24th, 2021. </ref>
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| ==Morphologic Features==
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| HHV8-infected plasmablasts are the characteristic features of HHV8 Multicentric Castleman disease.<ref name=":2" /> Plasmablasts are present in the lymph node and spleen.<ref name=":0" /> 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.<ref name=":1" /> 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.<ref name=":1" /> 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.<ref name=":1" /> Sheets of mature plasma cells may be seen expanding the interfollicular region, some such cells may display cytoplasmic inclusions (Russell bodies) or crystalline forms.<ref name=":1" /> With disease progression, the plasmablasts increase in number and may coalesce to form clusters.<ref name=":1" /> 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.<ref name=":1" /> Plasmablastic aggregates that develop during disease progression may be oligoclonal or monoclonal.
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| ==Immunophenotype==
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| {| class="wikitable sortable"
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| !Finding!!Marker
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| |Positive (universal)||HHV 8 LANA 1, strong c IgM expression with lambda light chain restriction, CD20+/-, CD 79a -/+ <ref name=":1" />
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| |Positive (subset)||Viral IL-6 <ref name=":1" />
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| |Negative (universal)||CD 138, PAX 5, CD38-/+, CD27, EBV encoded small RNA <ref name=":1" />
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| |Negative (subset)||None
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| |} | | |} |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> |
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| No known recurrent abnormalities | | No known recurrent abnormalities |
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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.}}</blockquote> | | <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.}}</blockquote> |
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| No known recurrent abnormalities | | No known recurrent abnormalities |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Patterns|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Characteristic Chromosomal Patterns|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> |
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| No known recurrent abnormalities | | No known recurrent abnormalities |
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| |}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. | | |}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. |
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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.}}</blockquote> | | <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.}}</blockquote> |
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| No known recurrent abnormalities | | No known recurrent abnormalities |
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| <blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> | | <blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the previous version of the page. Please incorporate above.}}</blockquote> |
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| No known recurrent abnormalities | | No known recurrent abnormalities |
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| <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>. | | <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>. |
| [[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases K]] | | [[Category:HAEM5]] |
| | [[Category:DISEASE]] |
| | [[Category:Diseases K]] |
