Bailey.Glen: Created page with " ==Primary Author(s)*== Mark Evans, MD (University of California, Irvine) Fabiola Quintero-Rivera, MD (University of California, Irvine) TOC ==Cancer Category/Type==..."

2023-11-03T17:46:01Z

Created page with " ==Primary Author(s)*== Mark Evans, MD (University of California, Irvine) Fabiola Quintero-Rivera, MD (University of California, Irvine) __TOC__ ==Cancer Category/Type==..."

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==Primary Author(s)*==

Mark Evans, MD (University of California, Irvine)

Fabiola Quintero-Rivera, MD (University of California, Irvine)

__TOC__

==Cancer Category/Type==

Mature B-cell neoplasm

==Cancer Sub-Classification / Subtype==

Plasma cell neoplasm

==Definition / Description of Disease==

In 1997, Delecluse et al. described a series of large B-cell lymphomas occurring within the jaw and oral cavities of HIV-positive individuals<ref>{{Cite journal|last=Delecluse|first=H. J.|last2=Anagnostopoulos|first2=I.|last3=Dallenbach|first3=F.|last4=Hummel|first4=M.|last5=Marafioti|first5=T.|last6=Schneider|first6=U.|last7=Huhn|first7=D.|last8=Schmidt-Westhausen|first8=A.|last9=Reichart|first9=P. A.|date=1997|title=Plasmablastic lymphomas of the oral cavity: a new entity associated with the human immunodeficiency virus infection|url=https://www.ncbi.nlm.nih.gov/pubmed/9028965|journal=Blood|volume=89|issue=4|pages=1413–1420|issn=0006-4971|pmid=9028965}}</ref>. The cells were blastic in appearance and did not express CD20, but did demonstrate plasmacytic antigens. Plasmablastic lymphoma (PBL) is recognized by the World Health Organization (WHO) as an aggressive proliferation of large B cells with immunoblastic or plasmablastic morphology and plasmacytic phenotype<ref name=":0">Campo, E.; et al. (2016). Plasmablastic lymphoma. in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Revised 4th edition. Swerdlow, S.H.; Campo, E.; Harris, N.L.; Jaffe, E.S.; et al. Editors. IARC Press: Lyon, France. p 321-322.</ref>. This entity is distinguished from other large B-cell lymphomas with similar immunoprofiles, such as ALK-positive large B-cell lymphoma and HHV-8-associated lymphoproliferative disorders.

==Synonyms / Terminology==

Monomorphic plasmablastic lymphoma; plasmablastic lymphoma with plasmacytic differentiation

==Epidemiology / Prevalence==

*Plasmablastic lymphoma typically occurs in adults with human immunodeficiency virus (HIV) infection (approximately 73% of cases)<ref name=":1">{{Cite journal|last=Castillo|first=Jorge J.|last2=Bibas|first2=Michele|last3=Miranda|first3=Roberto N.|date=2015|title=The biology and treatment of plasmablastic lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/25636338|journal=Blood|volume=125|issue=15|pages=2323–2330|doi=10.1182/blood-2014-10-567479|issn=1528-0020|pmid=25636338}}</ref>.

*It is also seen in the setting of iatrogenic immunosuppression (autoimmune disease or post-transplant)<ref>{{Cite journal|last=Borenstein|first=J.|last2=Pezzella|first2=F.|last3=Gatter|first3=K. C.|date=2007|title=Plasmablastic lymphomas may occur as post-transplant lymphoproliferative disorders|url=https://www.ncbi.nlm.nih.gov/pubmed/17944927|journal=Histopathology|volume=51|issue=6|pages=774–777|doi=10.1111/j.1365-2559.2007.02870.x|issn=0309-0167|pmid=17944927}}</ref>.

*PBL has been observed in older immunocompetent adults and in children, typically with HIV or immunodeficiency<ref name=":2">{{Cite journal|last=Colomo|first=Lluís|last2=Loong|first2=Florence|last3=Rives|first3=Susana|last4=Pittaluga|first4=Stefania|last5=Martínez|first5=Antonio|last6=López-Guillermo|first6=Armando|last7=Ojanguren|first7=Jesús|last8=Romagosa|first8=Vicens|last9=Jaffe|first9=Elaine S.|date=2004|title=Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities|url=https://www.ncbi.nlm.nih.gov/pubmed/15166665|journal=The American Journal of Surgical Pathology|volume=28|issue=6|pages=736–747|doi=10.1097/01.pas.0000126781.87158.e3|issn=0147-5185|pmid=15166665}}</ref><ref>{{Cite journal|last=Liu|first=Fang|last2=Asano|first2=Naoko|last3=Tatematsu|first3=Akiko|last4=Oyama|first4=Takashi|last5=Kitamura|first5=Kunio|last6=Suzuki|first6=Kotaro|last7=Yamamoto|first7=Kazuhito|last8=Sakamoto|first8=Natsumi|last9=Taniwaki|first9=Masafumi|date=2012|title=Plasmablastic lymphoma of the elderly: a clinicopathological comparison with age-related Epstein-Barr virus-associated B cell lymphoproliferative disorder|url=https://www.ncbi.nlm.nih.gov/pubmed/22958176|journal=Histopathology|volume=61|issue=6|pages=1183–1197|doi=10.1111/j.1365-2559.2012.04339.x|issn=1365-2559|pmid=22958176}}</ref>.

==Clinical Features==

An extranodal mass is the most typical presentation, and nodal disease is more common in post-transplant PBL<ref name=":1" />. Paraproteins may be detected in some cases<ref name=":3">{{Cite journal|last=Taddesse-Heath|first=Lekidelu|last2=Meloni-Ehrig|first2=Aurelia|last3=Scheerle|first3=Jay|last4=Kelly|first4=JoAnn C.|last5=Jaffe|first5=Elaine S.|date=2010|title=Plasmablastic lymphoma with MYC translocation: evidence for a common pathway in the generation of plasmablastic features|url=https://www.ncbi.nlm.nih.gov/pubmed/20348882|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=23|issue=7|pages=991–999|doi=10.1038/modpathol.2010.72|issn=1530-0285|pmc=6344124|pmid=20348882}}</ref>. Greater than 50% of cases associated with some form of immunodeficiency present with stage III/IV disease with bone marrow involvement<ref name=":1" /><ref name=":2" />.

==Sites of Involvement==

Typically head and neck regions, particularly the oral cavity. Other less commonly involved sites include the gastrointestinal tract, skin, soft tissue, lung, bone, and rarely lymph nodes<ref name=":4">Campo, E. (2017). Plasmablastic neoplasms other than plasma cell myeloma. in Hematopathology. 2nd edition. Jaffe, E.S.; Arber, D.A.; Campo, E.; et al. Editors. Elsevier: Philadelphia. p 465-472.</ref>.
[[File:Plasmablastic lymphoma (H&E stain).jpg|thumb|(PBL, monomorphic variant; image courtesy of Mark Evans, MD)]]

==Morphologic Features==

Two histologic variants have been described:

*The monomorphic variant features large immunoblast-like cells with fine nuclear chromatin, prominent nucleoli, and little or no plasmacytic differentiation; a starry sky pattern is common.

*The variant with plasmacytic differentiation is composed of cells with course nuclear chromatin, basophilic cytoplasm, eccentric nuclei, and paranuclear hof.

*Some cases demonstrate features of both variants<ref name=":0" />.

==Immunophenotype==
[[File:Plasmablastic lymphoma (CD138 immunohistochemistry).jpg|thumb|(PBL strongly positive for CD138 by immunohistochemistry; image courtesy of Mark Evans, MD)]]
The cells express plasmacytic antigens (CD138, VS38c, IRF4/MUM1, BLIMP1, XBP1, and CD38). CD45, PAX-5, and CD20 are typically negative or weakly positive. Cytoplasmic IgG, as well as kappa and lambda light chains are common. CD79a is present in approximately 40% of cases, and CD56 in about 25%. The cells are typically positive for Epstein-Barr virus-encoded RNA (EBER). Ki-67 proliferation index is usually >90%<ref name=":4" /><ref>{{Cite journal|last=Montes-Moreno|first=Santiago|last2=Gonzalez-Medina|first2=Ana-Rosa|last3=Rodriguez-Pinilla|first3=Socorro-María|last4=Maestre|first4=Lorena|last5=Sanchez-Verde|first5=Lydia|last6=Roncador|first6=Giovanna|last7=Mollejo|first7=Manuela|last8=García|first8=Juan F.|last9=Menarguez|first9=Javier|date=2010|title=Aggressive large B-cell lymphoma with plasma cell differentiation: immunohistochemical characterization of plasmablastic lymphoma and diffuse large B-cell lymphoma with partial plasmablastic phenotype|url=https://www.ncbi.nlm.nih.gov/pubmed/20418245|journal=Haematologica|volume=95|issue=8|pages=1342–1349|doi=10.3324/haematol.2009.016113|issn=1592-8721|pmc=2913083|pmid=20418245}}</ref>.

==Chromosomal Rearrangements (Gene Fusions)==

''MYC'' (8q24) up-regulation occurs via translocations, frequently between ''MYC'' and immunoglobulin (''IG)'' heavy chain [t(8;14)] and immunoglobulin light chain genes [t(2;8) or t(8;22)], which are also seen in Burkitt lymphoma. These translocations are more common in EBV-positive tumors (74%), and have been associated with poorer prognosis<ref>{{Cite journal|last=Bogusz|first=Agata M.|last2=Seegmiller|first2=Adam C.|last3=Garcia|first3=Rolando|last4=Shang|first4=Ping|last5=Ashfaq|first5=Raheela|last6=Chen|first6=Weina|date=2009|title=Plasmablastic lymphomas with MYC/IgH rearrangement: report of three cases and review of the literature|url=https://www.ncbi.nlm.nih.gov/pubmed/19762538|journal=American Journal of Clinical Pathology|volume=132|issue=4|pages=597–605|doi=10.1309/AJCPFUR1BK0UODTS|issn=1943-7722|pmid=19762538}}</ref><ref name=":5">{{Cite journal|last=Valera|first=Alexandra|last2=Balagué|first2=Olga|last3=Colomo|first3=Luis|last4=Martínez|first4=Antonio|last5=Delabie|first5=Jan|last6=Taddesse-Heath|first6=Lekidelu|last7=Jaffe|first7=Elaine S.|last8=Campo|first8=Elías|date=2010|title=IG/MYC rearrangements are the main cytogenetic alteration in plasmablastic lymphomas|url=https://www.ncbi.nlm.nih.gov/pubmed/20962620|journal=The American Journal of Surgical Pathology|volume=34|issue=11|pages=1686–1694|doi=10.1097/PAS.0b013e3181f3e29f|issn=1532-0979|pmc=2982261|pmid=20962620}}</ref>.
[[File:MYC FISH of plasmablastic lymphoma.png|thumb|(Rearrangement of MYC by FISH (yellow signals); image courtesy of Fabiola Quintero-Rivera, MD)]]
==Characteristic Chromosomal Aberrations / Patterns==

In addition to the ''MYC/IG'' rearrangements, complex karyotypes are also frequently observed. PBL often demonstrates chromosomal changes seen in plasma cell myeloma, including gain of 1q, loss of 1p, deletions 13q and/or 17p, and gains of odd-numbered chromosomes, such as +3, +5, +7, +9, +11, and/or +15<ref name=":3" /><ref>Meloni-Ehrig, Aurelia; et al. (2017). “Plasmablastic lymphoma (PBL)”. Atlas Genet Cytogenet Oncol Haematol. '''21''' (2): 67-70.</ref>.

==Genomic Gain/Loss/LOH==

One study of 12 PBL cases showed recurrent gains of 1q31.1q44, 5p15.33p13.1, 7q11.2q11.23, 8q24.13q24.3, 11p and 11q terminal regions, 15q15q26.3, 19p13.3p13.12 and chromosomes 3, 7, 11, and 15, as well as losses of 1p36.33p35.1, 6q25.1q27, 8p23.3p22.14 and 18q21.32q23. Additionally, 54% of the cases had either deletion or copy neutral loss of heterozygosity (CN-LOH) involving the tumor suppressor gene ''CDKN2C'' at 1p32.3. Furthermore, recurrent copy number losses involving the immunoglobulin genes ''IGH'' and ''IGKV'' were documented<ref>{{Cite journal|last=Ji|first=Jianling|last2=Quintero-Rivera|first2=Fabiola|last3=Xian|first3=Rena|last4=Crane|first4=Genevieve|last5=Baden|first5=Kevin|last6=Moschiano|first6=Elizabeth|last7=Karunasiri|first7=Deepthi K.|last8=Duffield|first8=Amy Susan|last9=Rao|first9=Nagesh|date=2016-06|title=Genomic Profiling of Plasmablastic Lymphoma Reveals Recurrent Copy Number Alterations and MYC Rearrangement as Common Genetic Abnormalities|url=https://doi.org/10.1016/j.cancergen.2016.04.021|journal=Cancer Genetics|volume=209|issue=6|pages=290|doi=10.1016/j.cancergen.2016.04.021|issn=2210-7762}}</ref>.
[[File:MYC-IGH FISH of plasmablastic lymphoma.jpg|thumb|(Reciprocal translocation between the MYC and IGH loci by FISH (yellow signals); image courtesy of Fabiola Quintero-Rivera, MD) ]]
==Gene Mutations (SNV/INDEL)==

*''IGHV'' may be unmutated or demonstrate somatic hypermutation<ref>{{Cite journal|last=Gaidano|first=Gianluca|last2=Cerri|first2=Michaela|last3=Capello|first3=Daniela|last4=Berra|first4=Eva|last5=Deambrogi|first5=Clara|last6=Rossi|first6=Davide|last7=Larocca|first7=Luigi Maria|last8=Campo|first8=Elias|last9=Gloghini|first9=Annunziata|date=2002|title=Molecular histogenesis of plasmablastic lymphoma of the oral cavity|url=https://www.ncbi.nlm.nih.gov/pubmed/12437635|journal=British Journal of Haematology|volume=119|issue=3|pages=622–628|doi=10.1046/j.1365-2141.2002.03872.x|issn=0007-1048|pmid=12437635}}</ref>.

*Montes-Moreno et al. demonstrated somatic mutations in ''PRDM1(BLIMP1)'' in 50% of cases<ref>{{Cite journal|last=Montes-Moreno|first=Santiago|last2=Martinez-Magunacelaya|first2=Nerea|last3=Zecchini-Barrese|first3=Tomás|last4=Villambrosía|first4=Sonia Gonzalez de|last5=Linares|first5=Emma|last6=Ranchal|first6=Tamara|last7=Rodriguez-Pinilla|first7=María|last8=Batlle|first8=Ana|last9=Cereceda-Company|first9=Laura|date=2017|title=Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1|url=https://www.ncbi.nlm.nih.gov/pubmed/27687004|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=30|issue=1|pages=85–94|doi=10.1038/modpathol.2016.162|issn=1530-0285|pmid=27687004}}</ref>.

*The largest series of transplant-associated PBL analyzed by next-generation sequencing detected genetic aberrations of the ''RAS/MAPK'', ''TP53'', and ''NOTCH'' signaling pathways<ref>{{Cite journal|last=Bhagat|first=Govind|last2=Mansukhani|first2=Mahesh M.|last3=Alobeid|first3=Bachir|last4=Vundavalli|first4=Murty|last5=Hsiao|first5=Susan J.|last6=Raciti|first6=Patricia M.|last7=Leeman-Neill|first7=Rebecca J.|date=2017|title=Molecular Characterization of Post-Transplant Plasmablastic Lymphomas Implicates RAS, TP53, and NOTCH Mutations and MYC Deregulation in Disease Pathogenesis|url=https://ashpublications.org/blood/article/130/Supplement%201/4014/72609/Molecular-Characterization-of-Post-Transplant|journal=Blood|language=en|volume=130|issue=Supplement 1|pages=4014–4014|doi=10.1182/blood.V130.Suppl_1.4014.4014|issn=0006-4971}}</ref>.

==Epigenomics (Methylation)==

Hypermethylation of ''p16'' has been reported in a case of PBL<ref name=":6">{{Cite journal|last=Morscio|first=Julie|last2=Dierickx|first2=Daan|last3=Nijs|first3=Jan|last4=Verhoef|first4=Gregor|last5=Bittoun|first5=Emilie|last6=Vanoeteren|first6=Xanne|last7=Wlodarska|first7=Iwona|last8=Sagaert|first8=Xavier|last9=Tousseyn|first9=Thomas|date=2014|title=Clinicopathologic comparison of plasmablastic lymphoma in HIV-positive, immunocompetent, and posttransplant patients: single-center series of 25 cases and meta-analysis of 277 reported cases|url=https://www.ncbi.nlm.nih.gov/pubmed/24832164|journal=The American Journal of Surgical Pathology|volume=38|issue=7|pages=875–886|doi=10.1097/PAS.0000000000000234|issn=1532-0979|pmid=24832164}}</ref>.

==Genes and Main Pathways Involved==

*''MYC'' expression is suppressed by ''PRDM1 (''BLIMP1) in terminally differentiated B cells; ''BLIMP1'' encodes a transcriptional factor responsible for plasma cell differentiation<ref name=":5" />.

*The ''MYC'' activation present in PBL (by gene amplification or translocation) results in cellular proliferation and survival upon overcoming ''PRDM1 (''BLIMP1) repression.

==Diagnostic Testing Methods==

*Diagnosis is usually dependent on morphologic examination and immunohistochemistry demonstrating expression for plasmacytic antigens.

*Conventional cytogenetics has utility in detecting ''MYC'' rearrangement and amplification. Most common translocation involves ''MYC -IGH.''

*Next-generation sequencing is helpful for identifying single nucleotide variants of ''PRDM1'' and of genes in the of the ''RAS/MAPK'', ''TP53'', and ''NOTCH'' signaling pathways.

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

*The prognosis of PBL is very poor, with three quarters of patients dying with a median survival of 6-11 months<ref name=":1" /><ref name=":6" />.

*There is currently no standard therapy for PBL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) have been generally considered inadequate, and the National Comprehensive Cancer Network (NCCN) favors Hyper-CVAD-MA (hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone, and high-dose methotrexate and cytarabine), CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine), COMB (cyclophosphamide, Oncovin, methyl-CCNU, and bleomycin), and infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)<ref name=":5" /><ref>{{Cite journal|last=Zelenetz|first=Andrew D.|last2=Abramson|first2=Jeremy S.|last3=Advani|first3=Ranjana H.|last4=Andreadis|first4=C. Babis|last5=Bartlett|first5=Nancy|last6=Bellam|first6=Naresh|last7=Byrd|first7=John C.|last8=Czuczman|first8=Myron S.|last9=Fayad|first9=Luis E.|date=2011|title=Non-Hodgkin's lymphomas|url=https://www.ncbi.nlm.nih.gov/pubmed/21550968|journal=Journal of the National Comprehensive Cancer Network: JNCCN|volume=9|issue=5|pages=484–560|doi=10.6004/jnccn.2011.0046|issn=1540-1413|pmid=21550968}}</ref><ref>{{Cite journal|last=Koizumi|first=Yusuke|last2=Uehira|first2=Tomoko|last3=Ota|first3=Yasunori|last4=Ogawa|first4=Yoshihiko|last5=Yajima|first5=Keishiro|last6=Tanuma|first6=Junko|last7=Yotsumoto|first7=Mihoko|last8=Hagiwara|first8=Shotaro|last9=Ikegaya|first9=Satoshi|date=2016|title=Clinical and pathological aspects of human immunodeficiency virus-associated plasmablastic lymphoma: analysis of 24 cases|url=https://www.ncbi.nlm.nih.gov/pubmed/27604616|journal=International Journal of Hematology|volume=104|issue=6|pages=669–681|doi=10.1007/s12185-016-2082-3|issn=1865-3774|pmid=27604616}}</ref>.

*Patients with localized disease have a better prognosis, and these individuals can be managed by radiotherapy and doxorubicin-based chemotherapy with radiation therapy<ref>{{Cite journal|last=Phipps|first=C.|last2=Yeoh|first2=K. W.|last3=Lee|first3=Y. S.|last4=Nagarajan|first4=C.|last5=Gopalakrishnan|first5=S.|last6=Ho|first6=L. P.|last7=Hwang|first7=W. Y. K.|last8=Goh|first8=Y. T.|last9=Grigoropoulos|first9=N. F.|date=2017|title=Durable remission is achievable with localized treatment and reduction of immunosuppression in limited stage EBV-related plasmablastic lymphoma|url=https://www.ncbi.nlm.nih.gov/pubmed/28831541|journal=Annals of Hematology|volume=96|issue=11|pages=1959–1960|doi=10.1007/s00277-017-3109-4|issn=1432-0584|pmid=28831541}}</ref><ref>{{Cite journal|last=Pinnix|first=Chelsea C.|last2=Shah|first2=Jatin J.|last3=Chuang|first3=Hubert|last4=Costelloe|first4=Colleen M.|last5=Medeiros|first5=L. Jeffrey|last6=Wogan|first6=Christine F.|last7=Reed|first7=Valerie|last8=Smith|first8=Grace L.|last9=Milgrom|first9=Sarah|date=2016|title=Doxorubicin-Based Chemotherapy and Radiation Therapy Produces Favorable Outcomes in Limited-Stage Plasmablastic Lymphoma: A Single-Institution Review|url=https://www.ncbi.nlm.nih.gov/pubmed/26795083|journal=Clinical Lymphoma, Myeloma & Leukemia|volume=16|issue=3|pages=122–128|doi=10.1016/j.clml.2015.12.008|issn=2152-2669|pmid=26795083}}</ref>.

*Polychemotherapy is required for patients with disseminated disease; more than 50% achieve complete remissions (CRs), but approximately 70% die of progressive disease, with an event-free survival of 22 months, and an overall survival of 32 months<ref>{{Cite journal|last=Tchernonog|first=E.|last2=Faurie|first2=P.|last3=Coppo|first3=P.|last4=Monjanel|first4=H.|last5=Bonnet|first5=A.|last6=Algarte Génin|first6=M.|last7=Mercier|first7=M.|last8=Dupuis|first8=J.|last9=Bijou|first9=F.|date=2017|title=Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group|url=https://www.ncbi.nlm.nih.gov/pubmed/28031174|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=28|issue=4|pages=843–848|doi=10.1093/annonc/mdw684|issn=1569-8041|pmid=28031174}}</ref>.

==Familial Forms==

Not applicable.

==Links==

[[Lymphomas Associated with HIV Infection]]

''[[Myc|MYC]]'' in COSMIC (https://cancer.sanger.ac.uk/cell_lines/gene/analysis?ln=MYC)

==References==

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<references />

==Notes==
<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.

HAEM4Backup:Plasmablastic Lymphoma - Revision history

Bailey.Glen: Created page with " ==Primary Author(s)*== Mark Evans, MD (University of California, Irvine) Fabiola Quintero-Rivera, MD (University of California, Irvine) __TOC__ ==Cancer Category/Type==..."

Bailey.Glen: Created page with " ==Primary Author(s)*== Mark Evans, MD (University of California, Irvine) Fabiola Quintero-Rivera, MD (University of California, Irvine) TOC ==Cancer Category/Type==..."