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'''''To view the landing page of lymphoma, click [[Lymphoma|here]].'''''
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{{CMG}} {{AE}} {{AS}}
{{CMG}}; {{AE}} {{S.G.}}, {{AS}}; {{GRR}} {{Nat}}


{{SK}} Body cavity lymphoma; PEL
{{SK}} Body cavity lymphoma; PEL
   
   
==Overview==
==Overview==
Primary effusion lymphoma (PEL) is rare subtype of [[diffuse large B-cell lymphoma]] (DLBCL). Primary effusion lymphoma is a very fast-growing (aggressive) lymphoma usually confined to pleural, pericardial, peritoneal body cavities, presenting as serous effusions without detectable tumor masses, occurring primarily but not exclusively in HIV-infected patients. Lymphoma cells are found in the fluid in these body cavities. Primary effusion lymphoma is associated with [[human herpes virus 8]] (HHV8) infection and Epstein-Barr virus ([[EBV]]) infection. On microscopic histopathological analysis, neoplastic proliferation of large lymphoid cells with round to irregular nuclei, prominent nucleoli, and varying amounts of vacuolated cytoplasm are characteristic findings of primary effusion lymphoma. Primary effusion lymphoma is more commonly observed among young or middle aged patients. Males are more commonly affected with primary effusion lymphoma than females. Symptoms of primary effusion lymphoma may include [[fever]], [[fatigue]], [[weight loss]], [[night sweats]], painless swellings in the neck, axilla, groin, thorax, and abdomen, chest pain, abdomen pain, bones pain, and skin rash. A [[lymph node biopsy]] is diagnostic of primary effusion lymphoma. The mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].
 
Primary effusion lymphoma (PEL) is rare sub-type of [[diffuse large B-cell lymphoma]] ([[Diffuse large B cell lymphoma|DLBCL]]). Primary effusion lymphoma is a very fast-growing (aggressive) [[Lymphomas|lymphoma]] usually confined to [[Pleural cavity|pleural]], [[pericardial]], [[peritoneal]] [[Body cavity|body cavities]], presenting as [[serous]] effusions without [[Detectable warning|detectable]] [[tumor]] [[Mass|masses]]. It occurs primarily, but not exclusively, in [[Human Immunodeficiency Virus (HIV)|HIV-]][[infected]] [[Patient|patients]]. [[Lymphomas|Lymphoma]] [[Cell (biology)|cells]] are found in the fluid in these [[Human body|body]] [[Cavity|cavities]]. Primary effusion [[lymphoma]] is associated with [[human]] [[herpes]] [[virus]] [[human herpes virus 8|8]] ([[HHV-8|HHV8]]) [[infection]] and [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]]) [[infection]]. On [[microscopic]] [[histopathological]] [[analysis]], [[neoplastic]] [[proliferation]] of large [[lymphoid]] [[Cell (biology)|cells]] with round to irregular [[nuclei]], prominent [[nucleoli]], and varying amounts of vacuolated [[cytoplasm]] are characteristic findings of primary effusion lymphoma. Primary effusion lymphoma is more commonly observed among young or middle-aged patients and males are more commonly affected with PEL than females. [[Symptom|Symptoms]] may include [[fever]], [[fatigue]], [[weight loss]], [[night sweats]], [[pain]]<nowiki/>less [[Swelling (medical)|swellings]] in the neck, [[axilla]], [[groin]], [[Chest|thorax]], [[abdomen]], [[chest pain]], [[abdomen]] [[pain]], bone pain, and skin rash. A [[lymph node biopsy]] is generally used in diagnosis of primary effusion lymphoma and the mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].
==Historical Perspective==
* The association between [[AIDS]], [[Epstein Barr virus|Epstein-Barr virus]] ([[Epstein Barr virus|EBV]]) and primary effusion lymphoma (PEL) was described in 1989 by DM Knowles and his group.<ref name="pmid2537119">{{cite journal |vauthors=Knowles DM, Inghirami G, Ubriaco A, Dalla-Favera R |title=Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus |journal=Blood |volume=73 |issue=3 |pages=792–9 |date=February 1989 |pmid=2537119 |doi= |url=}}</ref>
* In 1995, Cesarman ''et al'' was the first scientist to identify the association between [[Kaposi's sarcoma-associated herpesvirus|KSHV]] [[DNA sequences]] within a distinct sub-type of [[AIDS]] and the development of primary effusion lymphoma (PEL).<ref name="pmid7700311">{{cite journal |vauthors=Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM |title=Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas |journal=N. Engl. J. Med. |volume=332 |issue=18 |pages=1186–91 |date=May 1995 |pmid=7700311 |doi=10.1056/NEJM199505043321802 |url=}}</ref>
* Primary effusion lymphoma (PEL) was designated  by Nador ''et al''  that is associated with [[HHV-8]]/[[KSHV]], in1996.<ref name="pmid8695812">{{cite journal |vauthors=Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, Knowles DM |title=Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus |journal=Blood |volume=88 |issue=2 |pages=645–56 |date=July 1996 |pmid=8695812 |doi= |url=}}</ref>
 
==Classification==
There is no established system for the classification of primary effusion lymphoma.


==Pathophysiology==
==Pathophysiology==
* Primary effusion lymphoma is associated with [[human herpes virus 8]] (HHV8) infection and  Epstein-Barr virus ([[EBV]]) infection.<ref name="canadiancancer">Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref>
* Primary effusion lymphoma is associated with [[human]] [[herpes]] [[virus]] [[human herpes virus 8|8]] ([[HHV-8|HHV8]]) [[infection]] and  [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]]) [[infection]].<ref name="canadiancancer">Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref><ref name="pmid29384100">{{cite journal |vauthors=Gruffat H, Manet E |title=[EBV/KSHV co-infection: an effective partnership] |language=French |journal=Med Sci (Paris) |volume=34 |issue=1 |pages=79–82 |date=January 2018 |pmid=29384100 |doi=10.1051/medsci/20183401017 |url=}}</ref>
* Primary effusion lymphoma most often occurs in immunodeficient patients such as those with [[HIV/AIDS]]. It can sometimes occur in people who have had organ transplants.
* Among a very few of patients with [[human]] [[herpes]] [[virus]] 8 ([[HHV-8|HHV8]]) not associated with an effusion (a solid variant of PEL).<ref name="HashmiMurray2018">{{cite journal|last1=Hashmi|first1=Hamza|last2=Murray|first2=Drew|last3=Al-Quran|first3=Samer|last4=Tse|first4=William|title=Primary Effusion Lymphoma without an Effusion: A Rare Case of Solid Extracavitary Variant of Primary Effusion Lymphoma in an HIV-Positive Patient|journal=Case Reports in Hematology|volume=2018|year=2018|pages=1–5|issn=2090-6560|doi=10.1155/2018/9368451}}</ref>
* On microscopic histopathological analysis, neoplastic proliferation of large lymphoid cells with round to irregular nuclei, prominent nucleoli, and varying amounts of vacuolated cytoplasm are characteristic findings of primary effusion lymphoma.  
* Primary effusion lymphoma most often occurs in [[Immunodeficiency|immunodeficient]] patients such as those with [[HIV/AIDS]]. It can sometimes occur in people who have had [[Organ transplant|organ transplants]].<ref name="AhmedVeeraraghavan2016">{{cite journal|last1=Ahmed|first1=Omar|last2=Veeraraghavan|first2=Srihari|title=Primary Effusion Lymphoma in Solid Organ Transplant Recipient|journal=Chest|volume=150|issue=4|year=2016|pages=758A|issn=00123692|doi=10.1016/j.chest.2016.08.853}}</ref>
* There were immunoblastic, plasmablastic and anaplastic variants with bizarre, pleomorphic nuclei.<ref name="biomedcentral">Primary effusion lymphona. BioMed Central. http://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-60. Accessed on March 23, 2016 </ref>
* On [[microscopic]] [[histopathological]] [[analysis]], [[neoplastic]] [[proliferation]] of large [[Lymphoid cell|lymphoid cells]] with round to irregular [[nuclei]], prominent [[nucleoli]], and varying amounts of vacuolated [[cytoplasm]] are characteristic findings of primary effusion lymphoma.<ref name="pmid29988764">{{cite journal |vauthors=Narkhede M, Arora S, Ujjani C |title=Primary effusion lymphoma: current perspectives |journal=Onco Targets Ther |volume=11 |issue= |pages=3747–3754 |date=2018 |pmid=29988764 |pmc=6029609 |doi=10.2147/OTT.S167392 |url=}}</ref>
* There were immunoblastic, plasmablastic and [[Anaplasia|anaplastic]] variants with bizarre, [[pleomorphic]] [[nuclei]].<ref name="biomedcentral">Primary effusion lymphona. BioMed Central. http://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-60. Accessed on March 23, 2016 </ref>


==Causes==
==Causes==
* There are no established causes for primary effusion lymphoma.
* There are no established causes for primary effusion lymphoma.
* PEL is always associated with HHV-8, also known as Kaposi sarcoma-associated herpes.
* PEL is always associated with [[HHV-8]], also known as [[Kaposi's Sarcoma|Kaposi]] [[sarcoma]] associated [[Herpes B virus|herpes]].<ref name="canadiancancer" /><ref name="pmid29384100" /><ref name="pmid29988764" />
* PEL is most commonly present in immunodeficient patients, especially those with advanced AIDS.
* PEL is most commonly present in immunodeficient patients, especially those with advanced [[HIV AIDS|AIDS]].<ref name="canadiancancer" /><ref name="pmid29384100" /><ref name="pmid29988764" />
* An infection with Epstein-Barr virus (EBV) is also present in the majority of PEL cases.
* An [[infection]] with [[Epstein Barr virus|Epstein-Barr virus]] ([[EBV]]) is also present in the majority of primary effusion lymphoma (PEL) cases.<ref name="pmid25364646">{{cite journal |vauthors=Okada S, Goto H, Yotsumoto M |title=Current status of treatment for primary effusion lymphoma |journal=Intractable Rare Dis Res |volume=3 |issue=3 |pages=65–74 |date=August 2014 |pmid=25364646 |pmc=4214239 |doi=10.5582/irdr.2014.01010 |url=}}</ref>


==Differentiating primary effusion lymphoma from other Diseases==
==Differentiating primary effusion lymphoma from other Diseases==
* Primary effusion lymphoma must be differentiated from other diseases such as:
* Primary effusion lymphoma must be differentiated from other [[Disease|diseases]] such as:<ref name="pmid299887642">{{cite journal |vauthors=Narkhede M, Arora S, Ujjani C |title=Primary effusion lymphoma: current perspectives |journal=Onco Targets Ther |volume=11 |issue= |pages=3747–3754 |date=2018 |pmid=29988764 |pmc=6029609 |doi=10.2147/OTT.S167392 |url=}}</ref><ref name="PatelXiao2013">{{cite journal|last1=Patel|first1=Sanjay|last2=Xiao|first2=Philip|title=Primary Effusion Lymphoma|journal=Archives of Pathology & Laboratory Medicine|volume=137|issue=8|year=2013|pages=1152–1154|issn=0003-9985|doi=10.5858/arpa.2012-0294-RS}}</ref>
:* Plasmablastic lymphoma
:* Plasmablastic lymphoma (PBL)
:* [[Burkitt lymphoma]]
:* [[Burkitt lymphoma]]
:* Pyothorax associated lymphoma
:* [[Pyothorax]] associated lymphoma (PAL)
:* [[Anaplastic large cell lymphoma]]
:* [[Anaplastic large cell lymphoma]] ([[ALCL]])
:* [[Diffuse large B cell lymphoma|Diffuse large B-cell lymphoma]]
:* [[Diffuse large B cell lymphoma|Diffuse large B-cell lymphoma]] ([[Diffuse large B cell lymphoma|DLBCL]])


==Epidemiology and Demographics==
==Epidemiology and Demographics==
* Primary effusion lymphoma is usually diagnosed among HIV infection. <ref name="pmid11917248" />
* Primary effusion lymphoma usually has same age and race of HIV patients.<ref name="pmid11917248">{{cite journal |vauthors=Mbulaiteye SM, Biggar RJ, Goedert JJ, Engels EA |title=Pleural and peritoneal lymphoma among people with AIDS in the United States |journal=J. Acquir. Immune Defic. Syndr. |volume=29 |issue=4 |pages=418–21 |date=April 2002 |pmid=11917248 |doi= |url=}}</ref>
There is no racial predilection to Primary effusion lymphoma.
=== Incidence ===
* The prevalence of primary effusion lymphoma is unknown.
* Primary effusion lymphoma accounts for less than 1% of non-AIDS related [[lymphomas]] and 4% of [[lymphomas]] associated with [[AIDS]].<ref name="pmid299887642" />
===Age===
===Age===
* Primary effusion lymphoma is more commonly observed among young or middle aged patients.<ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>
* Primary effusion lymphoma is more commonly observed among young or middle-aged patients.<ref name="pmid299887642" /><ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>
===Gender===
===Gender===
* Males are more commonly affected with primary effusion lymphoma than females.<ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>
* Males are more commonly affected with primary effusion lymphoma than female (6:1).<ref name="pmid299887642" /><ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016 </ref>


==Risk Factors==
==Risk Factors==
*There are no established risk factors for primary effusion lymphoma.


== Natural History, Complications and Prognosis==
The most potent [[risk factor]] in the development of primary effusion lymphoma is [[human]] [[herpes virus]] (HHV) [[infection]]. Other risk factors include [[Epstein Barr virus|Epstein-Barr virus]] ([[Epstein Barr virus|EBV]]) [[infection]], immunodeficient patients, and  [[HHV-8]] infection.
* Primary effusion lymphoma is a very fast-growing (aggressive) lymphoma usually confined to pleural, pericardial, peritoneal body cavities, presenting as serous effusions without detectable tumor masses, occurring primarily but not exclusively in HIV-infected patients.  
 
* Prognosis is generally poor.
Less common risk factors in the development of  primary effusion lymphoma include:<ref name="pmid299887642" /><ref name="pmid246087342">{{cite journal |vauthors=Antar A, El Hajj H, Jabbour M, Khalifeh I, El-Merhi F, Mahfouz R, Bazarbachi A |title=Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature |journal=Blood Cancer J |volume=4 |issue= |pages=e190 |date=March 2014 |pmid=24608734 |pmc=3972705 |doi=10.1038/bcj.2014.6 |url=}}</ref><ref name="MohammadSiddique2014">{{cite journal|last1=Mohammad|first1=Farhan|last2=Siddique|first2=Muhammad Neaman|last3=Siddiqui|first3=Faraz|last4=Popalzai|first4=M.|last5=Asgari|first5=Masoud|last6=Odaimi|first6=Marcel|title=A Unique Case of Malignant Pleuropericardial Effusion: HHV-8-Unrelated PEL-Like Lymphoma—A Case Report and Review of the Literature|journal=Case Reports in Oncological Medicine|volume=2014|year=2014|pages=1–5|issn=2090-6706|doi=10.1155/2014/436821}}</ref><ref name="pmid17071811">{{cite journal |vauthors=Inoue S, Miyamoto T, Yoshino T, Yamadori I, Hagari Y, Yamamoto O |title=Primary effusion lymphoma with skin involvement |journal=J. Clin. Pathol. |volume=59 |issue=11 |pages=1221–2 |date=November 2006 |pmid=17071811 |pmc=1860519 |doi=10.1136/jcp.2005.031807 |url=}}</ref>
** Male
** Age > 60 years
** [[Systemic]] [[disease]]
** Smoking
** [[Radiation (medicine)|Radiation]] and industrial [[Chemical|chemicals]]
** [[Chemotherapy]]
 
== Screening==
There is insufficient evidence to recommend routine screening for primary effusion lymphoma.
 
== Natural History, Complications, and Prognosis==
* Primary effusion lymphoma is a very fast-growing (aggressive) [[Lymphomas|lymphoma]].<ref name="AntarEl Hajj2014">{{cite journal|last1=Antar|first1=A|last2=El Hajj|first2=H|last3=Jabbour|first3=M|last4=Khalifeh|first4=I|last5=EL-Merhi|first5=F|last6=Mahfouz|first6=R|last7=Bazarbachi|first7=A|title=Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature|journal=Blood Cancer Journal|volume=4|issue=3|year=2014|pages=e190–e190|issn=2044-5385|doi=10.1038/bcj.2014.6}}</ref>
* They are usually confined to [[Pleural effusion|pleural]], [[Pericardial effusion|pericardial]], [[Peritoneal cavity|peritoneal]] [[Cavity|cavities]], presenting as serous effusions without detectable [[tumor]] [[Mass|masses]].<ref name="pmid299887642" />
* [[Prognosis]] is generally poor with average life expectancy of 3-4 months after [[diagnosis]].<ref>{{Cite journal
| author = [[Neeraj Saini]], [[Ephraim P. Hochberg]], [[Erica A. Linden]], [[Smita Jha]], [[Heinz K. Grohs]] & [[Aliyah R. Sohani]]
| title = HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature
| journal = [[Case reports in oncological medicine]]
| volume = 2013
| pages = 292301
| year = 2013
| month =
| doi = 10.1155/2013/292301
| pmid = 23401819
}}</ref>
 
== Diagnosis ==
== Diagnosis ==
* Among the patients who present with [[Medical sign|clinical signs]] of  PEL usually have [[Human Immunodeficiency Virus (HIV)|HIV]] [[infection]] or [[Kaposi's sarcoma-associated herpesvirus|Kaposi's sarcoma]] or [[Castleman's disease]].<ref name="ChenRahemtullah2007" />
* Primary effusion lymphoma [[Diagnosis|diagnosed]] by [[Pathology (disambiguation)|pathological]] [[analysis]] of involved [[Tissue (biology)|tissue]] .<ref name="ChenRahemtullah2007" />
* [[World Health Organization|WHO]] describe primary effusion lymphoma (PEL) cells bridge those of large cell immunoblastic [[Lymphoma, large-cell|lymphoma]], cells with [[basophilic]] [[cytoplasm]], large round to irregular [[nuclei]], prominent [[nucleoli]].
* [[CD]] [[Marker|Markers]] that found [[CD45]] but not usually lymphocyte markers such as [[CD19]], [[CD20]], [[CD79a]], [[CD3 (immunology)|CD3]], [[CD4]], or [[CD8]]. <ref name="pmid299887642" /><ref name="pmid191694062">{{cite journal |vauthors=Nemunaitis MC, Schussler JM, Shiller SM, Sloan LM, Mennel RG |title=Primary effusion lymphoma diagnosed by pericardiocentesis |journal=Proc (Bayl Univ Med Cent) |volume=22 |issue=1 |pages=77–80 |date=January 2009 |pmid=19169406 |pmc=2626366 |doi= |url=}}</ref>
===Diagnostic Study of Choice===
There are no established criteria for the diagnosis of Primary effusion lymphoma.
===Staging===
===Staging===
Staging for primary effusion lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>
Staging for primary effusion lymphoma is provided in the following table:<ref>{{Cite journal| doi = 10.1200/JCO.2013.54.8800| issn = 1527-7755| volume = 32| issue = 27| pages = 3059–3068| last1 = Cheson| first1 = Bruce D.| last2 = Fisher| first2 = Richard I.| last3 = Barrington| first3 = Sally F.| last4 = Cavalli| first4 = Franco| last5 = Schwartz| first5 = Lawrence H.| last6 = Zucca| first6 = Emanuele| last7 = Lister| first7 = T. Andrew| last8 = Alliance, Australasian Leukaemia and Lymphoma Group| last9 = Eastern Cooperative Oncology Group| last10 = European Mantle Cell Lymphoma Consortium| last11 = Italian Lymphoma Foundation| last12 = European Organisation for Research| last13 = Treatment of Cancer/Dutch Hemato-Oncology Group| last14 = Grupo Español de Médula Ósea| last15 = German High-Grade Lymphoma Study Group| last16 = German Hodgkin's Study Group| last17 = Japanese Lymphorra Study Group| last18 = Lymphoma Study Association| last19 = NCIC Clinical Trials Group| last20 = Nordic Lymphoma Study Group| last21 = Southwest Oncology Group| last22 = United Kingdom National Cancer Research Institute| title = Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification| journal = Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology| date = 2014-09-20| pmid = 25113753}}</ref>
Line 55: Line 107:
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I
| style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
| style="padding: 5px 5px; background: #F5F5F5;" | One node or a group of adjacent nodes
| style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal lesions without nodal involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Single extranodal [[Lesion|lesions]] without [[Nodal (protein)|nodal]] involvement
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II
| style="padding: 5px 5px; background: #F5F5F5;" | Stage II
| style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the diaphragm
| style="padding: 5px 5px; background: #F5F5F5;" | Two or more nodal groups on the same side of the [[Diaphragm (anatomy)|diaphragm]]
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Stage I or II by nodal extent with limited contiguous extranodal involvement
|-
|-
Line 68: Line 120:
|-
|-
| style="padding: 5px 5px; background: #F5F5F5;" | Stage III
| style="padding: 5px 5px; background: #F5F5F5;" | Stage III
| style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Nodes on both sides of the [[diaphragm]]; nodes above the [[Thoracic diaphragm|diaphragm]] with [[spleen]] involvement
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
| style="padding: 5px 5px; background: #F5F5F5;" | Not applicable
|-
|-
Line 76: Line 128:
|}
|}
   
   
=== Symptoms ===
=== History and Symptoms ===
*Symptoms of primary effusion lymphoma may include the following:<ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 22, 2016 </ref>
*Symptoms of primary effusion lymphoma may include the following:<ref name="pmid299887642" /><ref name="seer.cancer.gov">Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 22, 2016 </ref><ref>{{Cite journal
:* [[Fever]]
| author = [[Neeraj Saini]], [[Ephraim P. Hochberg]], [[Erica A. Linden]], [[Smita Jha]], [[Heinz K. Grohs]] & [[Aliyah R. Sohani]]
| title = HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature
| journal = [[Case reports in oncological medicine]]
| volume = 2013
| pages = 292301
| year = 2013
| month =
| doi = 10.1155/2013/292301
| pmid = 23401819
}}</ref>
:* [[Fever]]  
:* [[Fatigue]]
:* [[Fatigue]]
:* [[Weight loss]]
:* [[Weight loss]]
:* [[Night sweats]]
:* [[Night sweats]]
:* Painless swellings in the neck, axilla, groin, thorax, and abdomen
:* Painless [[Swelling (medical)|swellings]] in the [[neck]], [[axilla]], [[groin]], [[thorax]], and [[abdomen]]
:* Pain in the chest, abdomen, or bones
:* [[Pain]] in the [[chest]], [[abdomen]], or [[Bone|bones]]
:* Skin rash
:* [[Skin]] [[rash]]


=== Physical Examination ===
=== Physical Examination ===
*Physical examination of primary effusion lymphoma may be remarkable for:
*[[Physical examination]] of primary effusion lymphoma may be remarkable for:<ref name="pmid299887642" />
:* [[Fever]]
:* [[Fever]]
:* Skin rash  
:* [[Skin]] [[rash]]
:* [[Tachypnea]] 
:* [[Lymphadenopathy|Cervical lymphadenopathy]]
:* [[Lymphadenopathy|Cervical lymphadenopathy]]
:* Thoracic masses suggestive of [[Lymphadenopathy|central lymphadenopathy]]
:* [[Thoracic]] [[Mass|masses]] suggestive of central lymphadenopathy
:* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
:* [[Abdominal mass]]es suggestive of [[Lymphadenopathy|central lymphadenopathy]]
:* [[Lymphadenopathy|Peripheral lymphadenopathy]]
:* [[Lymphadenopathy|Peripheral lymphadenopathy]]
:* [[Lower extremity edema]]


=== Laboratory Findings ===
=== Laboratory Findings ===
*There are no specific laboratory findings associated with primary effusion lymphoma.
*There are no specific laboratory findings associated with primary effusion lymphoma.
*A lymph node biopsy is diagnostic of primary effusion lymphoma.
*PEL cells typically express a hematolymphoid [[marker]], [[CD45]].<ref name="pmid299887642" /><ref>{{Cite journal
*Other laboratory findings consistent with the diagnosis of primary effusion lymphoma include [[complete blood count]], blood chemistry studies, cytogenetic analysis, [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].
| author = [[Emmanuelle Boulanger]], [[Veronique Meignin]] & [[Eric Oksenhendler]]
| title = Bortezomib (PS-341) in patients with human herpesvirus 8-associated primary effusion lymphoma
| journal = [[British journal of haematology]]
| volume = 141
| issue = 4
| pages = 559–561
| year = 2008
| month = May
| doi = 10.1111/j.1365-2141.2008.07057.x
| pmid = 18341641
}}</ref><ref>{{Cite journal
| author = [[Neeraj Saini]], [[Ephraim P. Hochberg]], [[Erica A. Linden]], [[Smita Jha]], [[Heinz K. Grohs]] & [[Aliyah R. Sohani]]
| title = HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature
| journal = [[Case reports in oncological medicine]]
| volume = 2013
| pages = 292301
| year = 2013
| month =
| doi = 10.1155/2013/292301
| pmid = 23401819
}}</ref><ref name="ChenRahemtullah2007">{{cite journal|last1=Chen|first1=Y.-B.|last2=Rahemtullah|first2=A.|last3=Hochberg|first3=E.|title=Primary Effusion Lymphoma|journal=The Oncologist|volume=12|issue=5|year=2007|pages=569–576|issn=1083-7159|doi=10.1634/theoncologist.12-5-569}}</ref>


===Imaging Findings===
*A [[lymph node]] [[biopsy]] is [[diagnostic]] of primary effusion lymphoma.<ref name="pmid19169406">{{cite journal |vauthors=Nemunaitis MC, Schussler JM, Shiller SM, Sloan LM, Mennel RG |title=Primary effusion lymphoma diagnosed by pericardiocentesis |journal=Proc (Bayl Univ Med Cent) |volume=22 |issue=1 |pages=77–80 |date=January 2009 |pmid=19169406 |pmc=2626366 |doi= |url=}}</ref>
*Other [[Medical laboratory|laboratory]] findings consistent with the diagnosis of primary effusion lymphoma include [[complete blood count]], [[blood]] [[chemistry]] studies, [[Cytogenetics|cytogenetic]] [[analysis]], [[flow cytometry]], [[immunohistochemistry]], and [[immunophenotyping]].
 
===Electrocardiogram===
There are no ECG findings associated with Primary effusion lymphoma.
 
=== X-ray ===
There are no x-ray findings associated with Primary effusion lymphoma.
 
=== Echocardiography or Ultrasound ===
There are no echocardiography/ultrasound findings associated with Primary effusion lymphoma.
 
=== CT scan ===
There are no CT scan findings associated with Primary effusion lymphoma.
 
=== MRI ===
There are no MRI findings associated with Primary effusion lymphoma.
 
===Other Imaging Findings===
*There are no specific imaging study associated with primary effusion lymphoma.
*There are no specific imaging study associated with primary effusion lymphoma.
*[[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of primary effusion lymphoma.
*[[CT]], [[MRI]], and [[PET]] scan may be helpful in the diagnosis of primary effusion lymphoma.<ref name="pmid23284262">{{cite journal |vauthors=Buchpiguel CA |title=Current status of PET/CT in the diagnosis and follow up of lymphomas |journal=Rev Bras Hematol Hemoter |volume=33 |issue=2 |pages=140–7 |date=2011 |pmid=23284262 |pmc=3520639 |doi=10.5581/1516-8484.20110035 |url=}}</ref>


=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===
*Primary effusion lymphoma may also be diagnosed using [[bone marrow aspiraton]] and [[biopsy]].
*Primary effusion lymphoma may also be diagnosed using [[bone marrow]] aspiration and [[biopsy]].<ref name="AntonangeloVargas2005">{{cite journal|last1=Antonangelo|first1=Leila|last2=Vargas|first2=Francisco S|last3=Teixeira|first3=Lisete Ribeiro|last4=Vaz|first4=Marcelo A C|last5=Sales|first5=Maria Mirtes|last6=Moreira|first6=Luis C|last7=Sales|first7=Roberta Karla Barbosa de|title=Linfoma primário de cavidade pleural em paciente imunocompetente|journal=Jornal Brasileiro de Pneumologia|volume=31|issue=6|year=2005|pages=563–566|issn=1806-3713|doi=10.1590/S1806-37132005000600017}}</ref>


== Treatment ==
== Treatment ==
=== Medical Therapy ===
=== Medical Therapy ===
* The mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].<ref name="canadiancancer">Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref>
* The mainstay of therapy for primary effusion lymphoma is [[chemotherapy]] and [[antiretroviral therapy]].<ref name="canadiancancer">Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016 </ref><ref name="OkadaGoto2014">{{cite journal|last1=Okada|first1=Seiji|last2=Goto|first2=Hiroki|last3=Yotsumoto|first3=Mihoko|title=Current status of treatment for primary effusion lymphoma|journal=Intractable & Rare Diseases Research|volume=3|issue=3|year=2014|pages=65–74|issn=2186-3644|doi=10.5582/irdr.2014.01010}}</ref>
* Drug regimen: CHOP – [[Cyclophosphamide]] {{and}} [[Doxorubicin]] {{and}} [[Vincristine]] {{and}} [[Prednisone]]
* Drug regimen: CHOP – [[Cyclophosphamide]] {{and}} [[Doxorubicin]] {{and}} [[Vincristine]] {{and}} [[Prednisone]]
===Surgery===
Surgical intervention is not recommended for the management of primary effusion lymphoma.
=== Primary Prevention ===
There are no established measures for the primary prevention of primary effusion lymphoma.
=== Secondary Prevention ===
There are no established measures for the secondary prevention of primary effusion lymphoma.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 23:49, 29 July 2020


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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sogand Goudarzi, MD [2], Sowminya Arikapudi, M.B,B.S. [3]; Grammar Reviewer: Natalie Harpenau, B.S.[4]

Synonyms and keywords: Body cavity lymphoma; PEL

Overview

Primary effusion lymphoma (PEL) is rare sub-type of diffuse large B-cell lymphoma (DLBCL). Primary effusion lymphoma is a very fast-growing (aggressive) lymphoma usually confined to pleural, pericardial, peritoneal body cavities, presenting as serous effusions without detectable tumor masses. It occurs primarily, but not exclusively, in HIV-infected patients. Lymphoma cells are found in the fluid in these body cavities. Primary effusion lymphoma is associated with human herpes virus 8 (HHV8) infection and Epstein-Barr virus (EBV) infection. On microscopic histopathological analysis, neoplastic proliferation of large lymphoid cells with round to irregular nuclei, prominent nucleoli, and varying amounts of vacuolated cytoplasm are characteristic findings of primary effusion lymphoma. Primary effusion lymphoma is more commonly observed among young or middle-aged patients and males are more commonly affected with PEL than females. Symptoms may include fever, fatigue, weight loss, night sweats, painless swellings in the neck, axilla, groin, thorax, abdomen, chest pain, abdomen pain, bone pain, and skin rash. A lymph node biopsy is generally used in diagnosis of primary effusion lymphoma and the mainstay of therapy for primary effusion lymphoma is chemotherapy and antiretroviral therapy.

Historical Perspective

  • The association between AIDS, Epstein-Barr virus (EBV) and primary effusion lymphoma (PEL) was described in 1989 by DM Knowles and his group.[1]
  • In 1995, Cesarman et al was the first scientist to identify the association between KSHV DNA sequences within a distinct sub-type of AIDS and the development of primary effusion lymphoma (PEL).[2]
  • Primary effusion lymphoma (PEL) was designated by Nador et al that is associated with HHV-8/KSHV, in1996.[3]

Classification

There is no established system for the classification of primary effusion lymphoma.

Pathophysiology

Causes

Differentiating primary effusion lymphoma from other Diseases

  • Primary effusion lymphoma must be differentiated from other diseases such as:[11][12]

Epidemiology and Demographics

  • Primary effusion lymphoma is usually diagnosed among HIV infection. [13]
  • Primary effusion lymphoma usually has same age and race of HIV patients.[13]

There is no racial predilection to Primary effusion lymphoma.

Incidence

  • The prevalence of primary effusion lymphoma is unknown.

Age

  • Primary effusion lymphoma is more commonly observed among young or middle-aged patients.[11][14]

Gender

  • Males are more commonly affected with primary effusion lymphoma than female (6:1).[11][14]

Risk Factors

The most potent risk factor in the development of primary effusion lymphoma is human herpes virus (HHV) infection. Other risk factors include Epstein-Barr virus (EBV) infection, immunodeficient patients, and HHV-8 infection.

Less common risk factors in the development of primary effusion lymphoma include:[11][15][16][17]

Screening

There is insufficient evidence to recommend routine screening for primary effusion lymphoma.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

There are no established criteria for the diagnosis of Primary effusion lymphoma.

Staging

Staging for primary effusion lymphoma is provided in the following table:[22]

Revised staging system for primary nodal lymphomas (Lugano classification)
Stage Involvement Extranodal (E) status
Limited
Stage I One node or a group of adjacent nodes Single extranodal lesions without nodal involvement
Stage II Two or more nodal groups on the same side of the diaphragm Stage I or II by nodal extent with limited contiguous extranodal involvement
Stage II bulky II as above with "bulky" disease Not applicable
Advanced
Stage III Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement Not applicable
Stage IV Additional noncontiguous extralymphatic involvement Not applicable

History and Symptoms

  • Symptoms of primary effusion lymphoma may include the following:[11][14][23]

Physical Examination

Laboratory Findings

  • There are no specific laboratory findings associated with primary effusion lymphoma.
  • PEL cells typically express a hematolymphoid marker, CD45.[11][24][25][20]

Electrocardiogram

There are no ECG findings associated with Primary effusion lymphoma.

X-ray

There are no x-ray findings associated with Primary effusion lymphoma.

Echocardiography or Ultrasound

There are no echocardiography/ultrasound findings associated with Primary effusion lymphoma.

CT scan

There are no CT scan findings associated with Primary effusion lymphoma.

MRI

There are no MRI findings associated with Primary effusion lymphoma.

Other Imaging Findings

  • There are no specific imaging study associated with primary effusion lymphoma.
  • CT, MRI, and PET scan may be helpful in the diagnosis of primary effusion lymphoma.[27]

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Surgical intervention is not recommended for the management of primary effusion lymphoma.

Primary Prevention

There are no established measures for the primary prevention of primary effusion lymphoma.

Secondary Prevention

There are no established measures for the secondary prevention of primary effusion lymphoma.

References

  1. ↑ Knowles DM, Inghirami G, Ubriaco A, Dalla-Favera R (February 1989). "Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus". Blood. 73 (3): 792–9. PMID 2537119.
  2. ↑ Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM (May 1995). "Kaposi's sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas". N. Engl. J. Med. 332 (18): 1186–91. doi:10.1056/NEJM199505043321802. PMID 7700311.
  3. ↑ Nador RG, Cesarman E, Chadburn A, Dawson DB, Ansari MQ, Sald J, Knowles DM (July 1996). "Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus". Blood. 88 (2): 645–56. PMID 8695812.
  4. ↑ 4.0 4.1 4.2 4.3 Primary effusion lymphona. Canadian Cancer Society. http://www.cancer.ca/en/cancer-information/cancer-type/non-hodgkin-lymphoma/non-hodgkin-lymphoma/types-of-nhl/primary-effusion-lymphoma/?region=nb. Accessed on March 23, 2016
  5. ↑ 5.0 5.1 5.2 Gruffat H, Manet E (January 2018). "[EBV/KSHV co-infection: an effective partnership]". Med Sci (Paris) (in French). 34 (1): 79–82. doi:10.1051/medsci/20183401017. PMID 29384100.
  6. ↑ Hashmi, Hamza; Murray, Drew; Al-Quran, Samer; Tse, William (2018). "Primary Effusion Lymphoma without an Effusion: A Rare Case of Solid Extracavitary Variant of Primary Effusion Lymphoma in an HIV-Positive Patient". Case Reports in Hematology. 2018: 1–5. doi:10.1155/2018/9368451. ISSN 2090-6560.
  7. ↑ Ahmed, Omar; Veeraraghavan, Srihari (2016). "Primary Effusion Lymphoma in Solid Organ Transplant Recipient". Chest. 150 (4): 758A. doi:10.1016/j.chest.2016.08.853. ISSN 0012-3692.
  8. ↑ 8.0 8.1 8.2 Narkhede M, Arora S, Ujjani C (2018). "Primary effusion lymphoma: current perspectives". Onco Targets Ther. 11: 3747–3754. doi:10.2147/OTT.S167392. PMC 6029609. PMID 29988764.
  9. ↑ Primary effusion lymphona. BioMed Central. http://jmedicalcasereports.biomedcentral.com/articles/10.1186/1752-1947-5-60. Accessed on March 23, 2016
  10. ↑ Okada S, Goto H, Yotsumoto M (August 2014). "Current status of treatment for primary effusion lymphoma". Intractable Rare Dis Res. 3 (3): 65–74. doi:10.5582/irdr.2014.01010. PMC 4214239. PMID 25364646.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 11.5 11.6 11.7 11.8 11.9 Narkhede M, Arora S, Ujjani C (2018). "Primary effusion lymphoma: current perspectives". Onco Targets Ther. 11: 3747–3754. doi:10.2147/OTT.S167392. PMC 6029609. PMID 29988764.
  12. ↑ Patel, Sanjay; Xiao, Philip (2013). "Primary Effusion Lymphoma". Archives of Pathology & Laboratory Medicine. 137 (8): 1152–1154. doi:10.5858/arpa.2012-0294-RS. ISSN 0003-9985.
  13. ↑ 13.0 13.1 Mbulaiteye SM, Biggar RJ, Goedert JJ, Engels EA (April 2002). "Pleural and peritoneal lymphoma among people with AIDS in the United States". J. Acquir. Immune Defic. Syndr. 29 (4): 418–21. PMID 11917248.
  14. ↑ 14.0 14.1 14.2 Primary effusion lymphoma. Surveillance, Epidemiology, and End Results Program. http://seer.cancer.gov/seertools/hemelymph/51f6cf57e3e27c3994bd5378/. Accessed on March 23, 2016
  15. ↑ Antar A, El Hajj H, Jabbour M, Khalifeh I, El-Merhi F, Mahfouz R, Bazarbachi A (March 2014). "Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature". Blood Cancer J. 4: e190. doi:10.1038/bcj.2014.6. PMC 3972705. PMID 24608734.
  16. ↑ Mohammad, Farhan; Siddique, Muhammad Neaman; Siddiqui, Faraz; Popalzai, M.; Asgari, Masoud; Odaimi, Marcel (2014). "A Unique Case of Malignant Pleuropericardial Effusion: HHV-8-Unrelated PEL-Like Lymphoma—A Case Report and Review of the Literature". Case Reports in Oncological Medicine. 2014: 1–5. doi:10.1155/2014/436821. ISSN 2090-6706.
  17. ↑ Inoue S, Miyamoto T, Yoshino T, Yamadori I, Hagari Y, Yamamoto O (November 2006). "Primary effusion lymphoma with skin involvement". J. Clin. Pathol. 59 (11): 1221–2. doi:10.1136/jcp.2005.031807. PMC 1860519. PMID 17071811.
  18. ↑ Antar, A; El Hajj, H; Jabbour, M; Khalifeh, I; EL-Merhi, F; Mahfouz, R; Bazarbachi, A (2014). "Primary effusion lymphoma in an elderly patient effectively treated by lenalidomide: case report and review of literature". Blood Cancer Journal. 4 (3): e190–e190. doi:10.1038/bcj.2014.6. ISSN 2044-5385.
  19. ↑ Neeraj Saini, Ephraim P. Hochberg, Erica A. Linden, Smita Jha, Heinz K. Grohs & Aliyah R. Sohani (2013). "HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature". Case reports in oncological medicine. 2013: 292301. doi:10.1155/2013/292301. PMID 23401819.
  20. ↑ 20.0 20.1 20.2 Chen, Y.-B.; Rahemtullah, A.; Hochberg, E. (2007). "Primary Effusion Lymphoma". The Oncologist. 12 (5): 569–576. doi:10.1634/theoncologist.12-5-569. ISSN 1083-7159.
  21. ↑ Nemunaitis MC, Schussler JM, Shiller SM, Sloan LM, Mennel RG (January 2009). "Primary effusion lymphoma diagnosed by pericardiocentesis". Proc (Bayl Univ Med Cent). 22 (1): 77–80. PMC 2626366. PMID 19169406.
  22. ↑ Cheson, Bruce D.; Fisher, Richard I.; Barrington, Sally F.; Cavalli, Franco; Schwartz, Lawrence H.; Zucca, Emanuele; Lister, T. Andrew; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Español de Médula Ósea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute (2014-09-20). "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification". Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 32 (27): 3059–3068. doi:10.1200/JCO.2013.54.8800. ISSN 1527-7755. PMID 25113753.
  23. ↑ Neeraj Saini, Ephraim P. Hochberg, Erica A. Linden, Smita Jha, Heinz K. Grohs & Aliyah R. Sohani (2013). "HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature". Case reports in oncological medicine. 2013: 292301. doi:10.1155/2013/292301. PMID 23401819.
  24. ↑ Emmanuelle Boulanger, Veronique Meignin & Eric Oksenhendler (2008). "Bortezomib (PS-341) in patients with human herpesvirus 8-associated primary effusion lymphoma". British journal of haematology. 141 (4): 559–561. doi:10.1111/j.1365-2141.2008.07057.x. PMID 18341641. Unknown parameter |month= ignored (help)
  25. ↑ Neeraj Saini, Ephraim P. Hochberg, Erica A. Linden, Smita Jha, Heinz K. Grohs & Aliyah R. Sohani (2013). "HHV8-Negative Primary Effusion Lymphoma of B-Cell Lineage: Two Cases and a Comprehensive Review of the Literature". Case reports in oncological medicine. 2013: 292301. doi:10.1155/2013/292301. PMID 23401819.
  26. ↑ Nemunaitis MC, Schussler JM, Shiller SM, Sloan LM, Mennel RG (January 2009). "Primary effusion lymphoma diagnosed by pericardiocentesis". Proc (Bayl Univ Med Cent). 22 (1): 77–80. PMC 2626366. PMID 19169406.
  27. ↑ Buchpiguel CA (2011). "Current status of PET/CT in the diagnosis and follow up of lymphomas". Rev Bras Hematol Hemoter. 33 (2): 140–7. doi:10.5581/1516-8484.20110035. PMC 3520639. PMID 23284262.
  28. ↑ Antonangelo, Leila; Vargas, Francisco S; Teixeira, Lisete Ribeiro; Vaz, Marcelo A C; Sales, Maria Mirtes; Moreira, Luis C; Sales, Roberta Karla Barbosa de (2005). "Linfoma primário de cavidade pleural em paciente imunocompetente". Jornal Brasileiro de Pneumologia. 31 (6): 563–566. doi:10.1590/S1806-37132005000600017. ISSN 1806-3713.
  29. ↑ Okada, Seiji; Goto, Hiroki; Yotsumoto, Mihoko (2014). "Current status of treatment for primary effusion lymphoma". Intractable & Rare Diseases Research. 3 (3): 65–74. doi:10.5582/irdr.2014.01010. ISSN 2186-3644.
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