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Lymphomas associated with HIV infection are a heterogeneous group of aggressive B-cell non-Hodgkin lymphomas that arise in individuals with active HIV infection. They are not currently assigned a separate International Classification of Diseases for Oncology Code, instead they are grouped with other morphologically or phenotypically similar hematological malignancies in the WHO guidelines. <ref name=":0">{{Cite journal|last=Yarchoan|first=Robert|last2=Uldrick|first2=Thomas S.|date=2018-03-15|title=HIV-Associated Cancers and Related Diseases|url=https://pubmed.ncbi.nlm.nih.gov/29539283|journal=The New England Journal of Medicine|volume=378|issue=11|pages=1029–1041|doi=10.1056/NEJMra1615896|issn=1533-4406|pmc=6890231|pmid=29539283}}</ref> These diseases include, but are not limited to, lymphoproliferative disorders associated with Epstein-Barr virus (EBV) infected tumor cells such as plasmablastic lymphoma and primary effusion lymphoma. <ref name=":0" /> Diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and primary central nervous system (CNS) lymphoma are stage 3 (i.e. acquired immunodeficiency syndrome (AIDS))-defining illnesses, in the context of preexisting HIV infection. <ref>{{Cite journal|last=Centers for Disease Control and Prevention (CDC)|date=2014-04-11|title=Revised surveillance case definition for HIV infection--United States, 2014|url=https://pubmed.ncbi.nlm.nih.gov/24717910|journal=MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports|volume=63|issue=RR-03|pages=1–10|issn=1545-8601|pmid=24717910}}</ref> Hodgkin lymphoma is not an AIDS-defining illness, but the incidence of Hodgkin lymphoma is significantly increased in the context of HIV infection. Lymphomas associated with HIV infection can be categorized into the following groups:

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*[[Diffuse Large B-cell Lymphoma, Not Otherwise Specified|Diffuse large B-cell lymphoma (DLBCL)]]

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*[[HAEM4:Diffuse Large B-cell Lymphoma, Not Otherwise Specified|Diffuse large B-cell lymphoma (DLBCL)]]

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*[[Burkitt ~~Lymphoma~~|Burkitt lymphoma]]

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*[[HAEM5:Burkitt lymphoma|Burkitt lymphoma]]

*Primary CNS lymphoma

*Primary effusion lymphoma

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*[[Plasmablastic ~~Lymphoma~~|Plasmablastic lymphoma]]

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*[[HAEM5:Plasmablastic lymphoma|Plasmablastic lymphoma]]

*KSHV-associated multicentric Castleman disease

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*[[Hodgkin Lymphomas|Hodgkin lymphoma]]

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*[[HAEM4:Hodgkin Lymphomas|Hodgkin lymphoma]]

==Synonyms / Terminology==

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|CD4 < 200/μL <ref name=":2" />

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|[[Burkitt ~~Lymphoma~~|Burkitt lymphoma]]

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|[[HAEM5:Burkitt lymphoma|Burkitt lymphoma]]

|The initial presentation is often due to symptoms associated with tumor expansion at sites of extra-nodal involvement (e.g. GI symptoms and cytopenias), although B symptoms (i.e. fever, night sweats, and weight loss) are also common. <ref name=":3">{{Cite journal|last=Atallah-Yunes|first=Suheil Albert|last2=Murphy|first2=Dermot J.|last3=Noy|first3=Ariela|date=2020-08|title=HIV-associated Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32735838|journal=The Lancet. Haematology|volume=7|issue=8|pages=e594–e600|doi=10.1016/S2352-3026(20)30126-5|issn=2352-3026|pmid=32735838}}</ref>

|CD4 > 200/μL<ref name=":3" /><ref name=":2" />

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|Decreased <ref>{{Cite journal|last=Shimada|first=Kazuyuki|last2=Hayakawa|first2=Fumihiko|last3=Kiyoi|first3=Hitoshi|date=2018-11-01|title=Biology and management of primary effusion lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/30154110|journal=Blood|volume=132|issue=18|pages=1879–1888|doi=10.1182/blood-2018-03-791426|issn=1528-0020|pmid=30154110}}</ref><ref>{{Cite journal|last=Chen|first=Yi-Bin|last2=Rahemtullah|first2=Aliyah|last3=Hochberg|first3=Ephraim|date=2007-05|title=Primary effusion lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17522245|journal=The Oncologist|volume=12|issue=5|pages=569–576|doi=10.1634/theoncologist.12-5-569|issn=1083-7159|pmid=17522245}}</ref>

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|[[Plasmablastic ~~Lymphoma~~|Plasmablastic lymphoma]]

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|[[HAEM5:Plasmablastic lymphoma|Plasmablastic lymphoma]]

|Involvement of oral cavity and mandibular lesions are common. However, both nodal and extra-nodal manifestations may occur. <ref name=":0" />

|CD4 < 200/μL <ref name=":2" />

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|No correlation with CD4 count <ref name=":2" />

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|[[Hodgkin Lymphomas|Hodgkin lymphoma]]

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|[[HAEM4:Hodgkin Lymphomas|Hodgkin lymphoma]]

|Associated with advanced age. B symptoms are more common than in HIV-negative patients. <ref name=":0" /> Additionally, unusual presentations with extranodal symptoms may occur. <ref name=":0" />

|CD4 > 200/μL <ref name=":2" />

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- Non-germinal B-cell (mainly represented by activated/immunoblastic and plasmablastic variant): large blastic cells with a small basophilic cytoplasm and large nuclei. It presents Ki67-index higher than 80%. <ref name=":8" />

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|[[Burkitt ~~Lymphoma~~|Burkitt lymphoma]]

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|[[HAEM5:Burkitt lymphoma|Burkitt lymphoma]]

|Similar to endemic and sporadic Burkitt lymphoma; classical starry-sky appearance, with small cells with abundant basophilic cytoplasm, round nuclei with two to four nucleoli. Tumors display high mitotic activity, with Ki67-index of 95% or higher. Can display plasmacytoid differentiation. <ref name=":5" /><ref name=":3" /><ref name=":8" />

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|Monoclonal B-cell population, with mixed characteristics of anaplastic large-cell and plasmablastic lymphomas. <ref>{{Cite journal|last=Carbone|first=Antonino|last2=Cesarman|first2=Ethel|last3=Spina|first3=Michele|last4=Gloghini|first4=Annunziata|last5=Schulz|first5=Thomas F.|date=2009-02-05|title=HIV-associated lymphomas and gamma-herpesviruses|url=https://pubmed.ncbi.nlm.nih.gov/18955561|journal=Blood|volume=113|issue=6|pages=1213–1224|doi=10.1182/blood-2008-09-180315|issn=1528-0020|pmid=18955561}}</ref> Cytoplasm is abundant and basophilic, with a large nucleus and prominent nucleoli. <ref name=":13">{{Cite journal|last=Carbone|first=Antonino|last2=Gloghini|first2=Annunziata|date=2005-09|title=AIDS-related lymphomas: from pathogenesis to pathology|url=https://pubmed.ncbi.nlm.nih.gov/16115121|journal=British Journal of Haematology|volume=130|issue=5|pages=662–670|doi=10.1111/j.1365-2141.2005.05613.x|issn=0007-1048|pmid=16115121}}</ref>

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|[[Plasmablastic ~~Lymphoma~~|Plasmablastic lymphoma]]

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|[[HAEM5:Plasmablastic lymphoma|Plasmablastic lymphoma]]

|Features similar to activated B-cell DLBCL, a starry-sky pattern and/or high mitotic activity with Ki67-index > 80% may be seen. Malignant cells may be distinctive large plasmablasts with abundant basophilic cytoplasm and large nuclei. <ref name=":5" /><ref name=":13" />

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|Significant vascular proliferation and hyalinization is seen in lymph nodes, with germinal centers surrounded by lymphocytes arranged in onion-skin appearance. <ref name=":16" />

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|[[Hodgkin Lymphomas|Hodgkin lymphoma]]

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|[[HAEM4:Hodgkin Lymphomas|Hodgkin lymphoma]]

|Histologic features vary depending on CD4 count. In more severely immunocompromised individuals, there is a predominance of unfavorable histologic features (mixed cellularity and lymphocyte depletion), with unusually large proportions of Reed-Sternberg cells generally seen with EBV-coinfection. <ref name=":0" /><ref name=":14">{{Cite journal|last=Carbone|first=Antonino|last2=Gloghini|first2=Annunziata|last3=Serraino|first3=Diego|last4=Spina|first4=Michele|date=2009-01|title=HIV-associated Hodgkin lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19339934|journal=Current opinion in HIV and AIDS|volume=4|issue=1|pages=3–10|doi=10.1097/COH.0b013e32831a722b|issn=1746-6318|pmid=19339934}}</ref> Nodular sclerosis subtype is mostly seen in patients with higher CD4 count. <ref name=":14" />

|}

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|[[Diffuse large B-cell lymphoma|DLBCL]]||CD10+ <ref>{{Cite journal|last=Dunleavy|first=Kieron|last2=Wilson|first2=Wyndham H.|date=2012-04-05|title=How I treat HIV-associated lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22337719|journal=Blood|volume=119|issue=14|pages=3245–3255|doi=10.1182/blood-2011-08-373738|issn=1528-0020|pmc=3321851|pmid=22337719}}</ref>, CD20+ <ref name=":0" />, CD45+ <ref name=":15" />, CD30+, EBV+ <ref name=":15" />, LMP1+ <ref name=":15" />, BCL2+ <ref name=":15" />, BCL6+/- <ref name=":15" />, MUM1/IRF4+/- <ref name=":15" />, CD138+/- <ref name=":15" />

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|[[Burkitt ~~Lymphoma~~|Burkitt lymphoma]]||CD20+ <ref name=":0" />, CD10+ <ref name=":0" />, BCL6+ <ref name=":3" />, EBV+/- <ref name=":3" />, BCL2- <ref name=":3" />, CD30- <ref name=":15" />

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|[[HAEM5:Burkitt lymphoma|Burkitt lymphoma]]||CD20+ <ref name=":0" />, CD10+ <ref name=":0" />, BCL6+ <ref name=":3" />, EBV+/- <ref name=":3" />, BCL2- <ref name=":3" />, CD30- <ref name=":15" />

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|AIDS-related primary CNS lymphoma||CD10+ <ref name=":4" />, CD20+ <ref name=":0" />, BCL6+ <ref name=":4" />, MUM-1+ <ref name=":4" />, EBV+ <ref name=":0" />

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|Primary effusion lymphoma||CD45+ <ref name=":13" />, CD30+ <ref name=":13" />, CD38+ <ref name=":13" />, CD138+ <ref name=":15" />, IL-2 R beta <ref name=":13" />, EMA+ <ref name=":13" />, EBV+ <ref name=":0" />, HHV-8 <ref name=":0" />, CD19- <ref name=":13" />, CD20- <ref name=":0" />, CD79a- <ref name=":13" />, BCL6- <ref name=":15" />

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|[[Plasmablastic ~~Lymphoma~~|Plasmablastic lymphoma]]

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|[[HAEM5:Plasmablastic lymphoma|Plasmablastic lymphoma]]

|EBV+ <ref name=":0" />, CD38+ <ref name=":2" />, CD138+ <ref name=":2" />, MUM/IRF41+ <ref name=":2" />, EMA+,CD20- <ref name=":0" />, CD79a- <ref name=":13" />, PAX5- <ref name=":15" />, CD45 - <ref name=":13" />

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|HHV-8+ <ref name=":0" />, OCT2+ <ref name=":16" />, BLIMP1+ <ref name=":16" />, IRF4/MUM1+ <ref name=":16" /><ref name=":17">{{Cite journal|last=Carbone|first=Antonino|last2=Borok|first2=Margaret|last3=Damania|first3=Blossom|last4=Gloghini|first4=Annunziata|last5=Polizzotto|first5=Mark N.|last6=Jayanthan|first6=Raj K.|last7=Fajgenbaum|first7=David C.|last8=Bower|first8=Mark|date=2021-11-25|title=Castleman disease|url=https://pubmed.ncbi.nlm.nih.gov/34824298|journal=Nature Reviews. Disease Primers|volume=7|issue=1|pages=84|doi=10.1038/s41572-021-00317-7|issn=2056-676X|pmid=34824298}}</ref>, BCL6-<ref name=":17" />, CD138+/- <ref name=":17" />, CD79a- <ref name=":17" />, EBV-, PAX- <ref name=":16" />, BCL-6<ref name=":16" />

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|[[Hodgkin Lymphomas|Hodgkin lymphoma]]

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|[[HAEM4:Hodgkin Lymphomas|Hodgkin lymphoma]]

|CD138+, LMP1+ <ref name=":14" />, MUM1 IRF4+ <ref name=":14" />, BCL6- <ref name=":14" />, EBV+ <ref name=":0" /><ref name=":14" />

|}

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==Links==

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[[Diffuse Large B-cell Lymphoma, Not Otherwise Specified]]

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[[HAEM4:Diffuse Large B-cell Lymphoma, Not Otherwise Specified]]

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[[Burkitt ~~Lymphoma~~]]

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[[HAEM5:Burkitt lymphoma]]

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[[Plasmablastic ~~Lymphoma~~]]

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[[HAEM5:Plasmablastic lymphoma]]

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[[Hodgkin Lymphomas]]

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[[HAEM4:Hodgkin Lymphomas]]

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[[Primary ~~Diffuse Large~~ B-cell ~~Lymphoma~~ of ~~the CNS~~|Primary Diffuse Large B-Cell Lymphoma of the CNS]]

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[[HAEM5:Primary large B-cell lymphoma of immune-privileged sites|Primary Diffuse Large B-Cell Lymphoma of the CNS]]

==References==

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HAEM4:Lymphomas Associated with HIV Infection (view source)

Revision as of 16:42, 4 December 2023