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

{{DISPLAYTITLE:High-grade B-cell lymphoma, NOS}}

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==Primary Author(s)*==

==Clinical Features==

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|'''Signs and Symptoms'''

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|'''Laboratory Findings'''

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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" />.

!Notes

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|Yes

|No

|Yes

The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

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

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

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

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!Notes

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7

chr7:1- 159,335,973 [hg38]

chr7

|Yes

|No

Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).

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8

chr8:1-145,138,636 [hg38]

chr8

|No

|No

Common recurrent secondary finding for t(8;21) (add reference).

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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.  

==Characteristic Chromosomal Patterns==

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!Notes

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Co-deletion of 1p and 18q

|No

|No

See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

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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" />.

==Gene Mutations (SNV / INDEL)==

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!Notes

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EGFR; Exon 20 mutations

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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>.

==Genes and Main Pathways Involved==

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!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

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''MYC''