HAEM5:High-grade B-cell lymphoma, NOS: Difference between revisions

Patients with HGBL, NOS typically present with clinically aggressive, advanced-stage disease, characterized by a high International Prognostic Index (IPI), and short survival. Both extranodal involvement and increased serum lactate dehydrogenase are common<ref name=":1" /><ref name=":2">{{Cite journal|last=Li|first=Shaoying|last2=Seegmiller|first2=Adam C.|last3=Lin|first3=Pei|last4=Wang|first4=Xuan J.|last5=Miranda|first5=Roberto N.|last6=Bhagavathi|first6=Sharathkumar|last7=Medeiros|first7=L. Jeffrey|date=2015-02|title=B-cell lymphomas with concurrent MYC and BCL2 abnormalities other than translocations behave similarly to MYC/BCL2 double-hit lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/25103070|journal=Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc|volume=28|issue=2|pages=208–217|doi=10.1038/modpathol.2014.95|issn=1530-0285|pmid=25103070}}</ref><ref name=":3">{{Cite journal|last=Perry|first=Anamarija M.|last2=Crockett|first2=David|last3=Dave|first3=Bhavana J.|last4=Althof|first4=Pamela|last5=Winkler|first5=Lisa|last6=Smith|first6=Lynette M.|last7=Aoun|first7=Patricia|last8=Chan|first8=Wing C.|last9=Fu|first9=Kai|date=2013-07|title=B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and burkitt lymphoma: study of 39 cases|url=https://pubmed.ncbi.nlm.nih.gov/23600716|journal=British Journal of Haematology|volume=162|issue=1|pages=40–49|doi=10.1111/bjh.12343|issn=1365-2141|pmid=23600716}}</ref>. Clinical signs can include unexplained fever, lymphadenopathy, night sweats, decreased body mass, abdominal pain, and abdominal distension<ref name=":1" />.

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==Sites of Involvement==

There are no recurrent chromosomal rearrangements associated with HGBL, NOS.

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

HGBL, NOS is associated with an aggressive clinical course with poor prognosis. Some studies suggest that despite the poor prognosis, clinical outcomes may be slightly better than those of HGBL with ''MYC'' and ''BCL2'' and/or ''BCL6'' rearrangements<ref name=":3" /><ref>{{Cite journal|last=Lin|first=Pei|last2=Dickason|first2=Timothy J.|last3=Fayad|first3=Luis E.|last4=Lennon|first4=Patrick A.|last5=Hu|first5=Peter|last6=Garcia|first6=Mar|last7=Routbort|first7=Mark J.|last8=Miranda|first8=Roberto|last9=Wang|first9=Xumei|date=2012-03-15|title=Prognostic value of MYC rearrangement in cases of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21882178|journal=Cancer|volume=118|issue=6|pages=1566–1573|doi=10.1002/cncr.26433|issn=1097-0142|pmid=21882178}}</ref><ref>{{Cite journal|last=Cook|first=James R.|last2=Goldman|first2=Bryan|last3=Tubbs|first3=Raymond R.|last4=Rimsza|first4=Lisa|last5=Leblanc|first5=Michael|last6=Stiff|first6=Patrick|last7=Fisher|first7=Richard|date=2014-04|title=Clinical significance of MYC expression and/or "high-grade" morphology in non-Burkitt, diffuse aggressive B-cell lymphomas: a SWOG S9704 correlative study|url=https://pubmed.ncbi.nlm.nih.gov/24625415|journal=The American Journal of Surgical Pathology|volume=38|issue=4|pages=494–501|doi=10.1097/PAS.0000000000000147|issn=1532-0979|pmc=3955880|pmid=24625415}}</ref>. Patients with double-expressor lymphoma (DHL) or a ''MYC'' rearrangement (SHL) have shown inferior overall survival than those without them in this entity<ref name=":1" />. A prognostic significance of various factors such as morphology of the tumor cells, types of genetic abnormalities and ''MYC'' translocation partner remains not fully understood since subgroup analysis is very limited and studies on this aspect have been conducted mainly in DLBCL cases<ref name=":0" /><ref>{{Cite journal|last=Rosenwald|first=Andreas|last2=Bens|first2=Susanne|last3=Advani|first3=Ranjana|last4=Barrans|first4=Sharon|last5=Copie-Bergman|first5=Christiane|last6=Elsensohn|first6=Mad-Helenie|last7=Natkunam|first7=Yaso|last8=Calaminici|first8=Maria|last9=Sander|first9=Birgitta|date=2019-12-10|title=Prognostic Significance of MYC Rearrangement and Translocation Partner in Diffuse Large B-Cell Lymphoma: A Study by the Lunenburg Lymphoma Biomarker Consortium|url=https://pubmed.ncbi.nlm.nih.gov/31498031|journal=Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology|volume=37|issue=35|pages=3359–3368|doi=10.1200/JCO.19.00743|issn=1527-7755|pmid=31498031}}</ref>.

There is no established standard therapy. In some studies patients treated with a high-intensity chemotherapy (DA-EPOCH-R, R-CODOX-M/IVAC, or R-Hyper-CVAD) have shown better clinical outcomes than those treated with R-CHOP, but further studies are needed to establish optimal treatment<ref name=":1" />.

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

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The 11q-gain/loss aberration has been reported in two cases of HGBL, NOS with ''MYC'' rearrangement<ref name=":5">{{Cite journal|last=Grygalewicz|first=Beata|last2=Woroniecka|first2=Renata|last3=Rymkiewicz|first3=Grzegorz|last4=Rygier|first4=Jolanta|last5=Borkowska|first5=Klaudia|last6=Kotyl|first6=Aleksandra|last7=Blachnio|first7=Katarzyna|last8=Bystydzienski|first8=Zbigniew|last9=Nowakowska|first9=Beata|date=2017-12-20|title=The 11q-Gain/Loss Aberration Occurs Recurrently in MYC-Negative Burkitt-like Lymphoma With 11q Aberration, as Well as MYC-Positive Burkitt Lymphoma and MYC-Positive High-Grade B-Cell Lymphoma, NOS|url=https://pubmed.ncbi.nlm.nih.gov/29272887|journal=American Journal of Clinical Pathology|volume=149|issue=1|pages=17–28|doi=10.1093/ajcp/aqx139|issn=1943-7722|pmc=5848380|pmid=29272887}}</ref>. The 11q gains in these cases were larger than 50 Mbp, with accompanying 10-18 Mbp terminal telomeric losses. Overlapping duplicated and deleted regions of these cases were shown in the table.  

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==Characteristic Chromosomal Patterns==

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This entity is genetically heterogeneous and the karyotype is often complex. By definition, concurrent ''MYC'' and ''BCL2'' or ''BCL6'' rearrangements are not seen. Isolated ''MYC'' rearrangement is common, being present in 20-35% of cases<ref name=":0" /><ref name=":1" /><ref name=":3" /><ref name=":4" />. Similarly, isolated rearrangements of ''BCL2'' or/and ''BCL6'' have been reported, occurring 14%-25% of reported cases. Copy number changes or amplification of ''MYC, BCL2'', or/and ''BCL6'' have been reported approximately in 20% of cases<ref name=":1" /><ref name=":3" /><ref name=":4" />. 27-29% of cases do not display any copy number or structural abnormalities involving ''MYC'', ''BCL2'', or ''BCL6''<ref name=":1" /><ref name=":3" />.

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==Gene Mutations (SNV / INDEL)==

There are few focused studies of sequence variation in HGBL, NOS. One study investigated nine cases, interrogating 13 genes that are frequently mutated in either BL or DLBCL. Variants in ''ID3, CCND3, MYC, BCL2'', ''CREBBP'', and ''SGK1'' were found in these cases, indicating their variant profiles overlap with those of BL and DLBCL. Although the sample size was small, it is noteworthy that ''ID3'' mutations were found in all eight cases with isolated ''MYC'' rearrangements<ref name=":6">{{Cite journal|last=Momose|first=S.|last2=Weißbach|first2=S.|last3=Pischimarov|first3=J.|last4=Nedeva|first4=T.|last5=Bach|first5=E.|last6=Rudelius|first6=M.|last7=Geissinger|first7=E.|last8=Staiger|first8=A. M.|last9=Ott|first9=G.|date=2015-08|title=The diagnostic gray zone between Burkitt lymphoma and diffuse large B-cell lymphoma is also a gray zone of the mutational spectrum|url=https://pubmed.ncbi.nlm.nih.gov/25673238|journal=Leukemia|volume=29|issue=8|pages=1789–1791|doi=10.1038/leu.2015.34|issn=1476-5551|pmid=25673238}}</ref>.

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==Epigenomic Alterations==

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''MYC''

''SGK1''  

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==Genetic Diagnostic Testing Methods==