HAEM5:Plasmablastic lymphoma: Difference between revisions

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" />.

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==Sites of Involvement==

[[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>.

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==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)]]

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

*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" />.

*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>.

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==Individual Region Genomic Gain / Loss / LOH==

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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) ]]

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==Characteristic Chromosomal Patterns==

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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>.

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==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>.

*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>.

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==Epigenomic Alterations==

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*''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.

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==Genetic Diagnostic Testing Methods==