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

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]

<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:High-Grade B-cell Lymphoma, Not Otherwise Specified (NOS)]].

 

==Cancer Category/Type==

 

 

==Cancer Sub-Classification / Subtype==

 

High-Grade B-cell Lymphoma, Not Otherwise Specified (NOS)

 

 

High-Grade B-cell Lymphoma, Not Otherwise Specified (HGBL, NOS) was a new entity in the 2016 WHO classification of Tumours of Haematopoietic and Lymphoid Tissues<ref name=":0">Kluin PM, et al., (2017). High-grade B-cell lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p340-341.</ref>, partially replacing ‘B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma and Burkitt lymphoma (BCLU)’, which was defined in the 2008 WHO edition. This entity consists of a heterogeneous group of aggressive mature B-cell lymphomas. HGBL, NOS lacks the combination of rearrangements required for categorization as ‘High-grade B-cell lymphoma with ''MYC'' and ''BCL2'' and/or ''BCL6'' rearrangements’, and does not meet the criteria for a diagnosis of diffuse large B-cell lymphoma (DLBCL), or Burkitt lymphoma (BL). Given this is a relatively newly defined entity, further refinement may occur over time as more data emerges.

 

 

 

HGBL, NOS is rare in the context of other aggressive lymphomas. The true incidence is unknown, since in the literature this entity has commonly been grouped together with HGBL with ''MYC'' and ''BCL2'' and/or ''BCL6'' rearrangements. In general, affected patients are older adults (≥60 years), with incidence increasing with age. Both males and females are affected<ref name=":0" />. A study of 41 cases showed the median age of onset was 41 (range of 12 to 79). This study also showed slightly higher incidence in males (63%) than females (37%)<ref name=":1">{{Cite journal|last=Li|first=Jiayin|last2=Liu|first2=Xiaoyin|last3=Yao|first3=Zhihua|last4=Zhang|first4=Mingzhi|date=2020|title=High-Grade B-Cell Lymphomas, Not Otherwise Specified: A Study of 41 Cases|url=https://pubmed.ncbi.nlm.nih.gov/32214848|journal=Cancer Management and Research|volume=12|pages=1903–1912|doi=10.2147/CMAR.S243753|issn=1179-1322|pmc=7082796|pmid=32214848}}</ref>.

==Clinical Features==

|'''Signs and Symptoms'''

|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

 

 

 

|'''Laboratory Findings'''

|EXAMPLE Cytopenias

 

!Finding!!Marker

|Positive (universal)||Pan B-cell markers such as CD19, CD20, and CD22

|Positive (subset)||CD10, Ki-67, MYC, BCL2, BCL6, IRF4/MUM1

|Negative (universal)||TdT, CD34, CCND1

|-

|Negative (subset)||CD10, Ki-67, MYC, BCL2, BCL6, IRF4/MUM1

Put your text here and fill in the table

!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)

|Yes

|No

|Yes

|EXAMPLE

 

<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}

<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:

* Gene Mutations (SNV/INDEL)}}

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>.

!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|EXAMPLE Loss

|EXAMPLE

 

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

 

|Yes

|Yes

|No

|EXAMPLE

 

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).

|EXAMPLE

 

|EXAMPLE Gain

|EXAMPLE

 

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

 

|No

|No

|No

|EXAMPLE

 

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

<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}

==Characteristic Chromosomal Patterns==

!Diagnostic Significance (Yes, No or Unknown)

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE

 

|Yes

|EXAMPLE:

 

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

<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}

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; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC /  TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''

!'''Diagnostic Significance (Yes, No or Unknown)'''

!Prognostic Significance (Yes, No or Unknown)

!Therapeutic Significance (Yes, No or Unknown)

!Notes

|EXAMPLE: TP53; Variable LOF mutations

EXAMPLE:

 

EGFR; Exon 20 mutations

 

EXAMPLE: BRAF; Activating mutations

|EXAMPLE: TSG

|EXAMPLE: 20% (COSMIC)

 

EXAMPLE: 30% (add Reference)

|EXAMPLE: IDH1 R123H

|EXAMPLE: EGFR amplification

|}

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

 

<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>

|EXAMPLE: BRAF and MAP2K1; Activating mutations

|EXAMPLE: MAPK signaling

|EXAMPLE: Increased cell growth and proliferation

|EXAMPLE: CDKN2A; Inactivating mutations

|EXAMPLE: Cell cycle regulation

|EXAMPLE: Unregulated cell division

|EXAMPLE:  KMT2C and ARID1A; Inactivating mutations

|EXAMPLE:  Histone modification, chromatin remodeling

|EXAMPLE:  Abnormal gene expression program

<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}

[[High-Grade B-cell Lymphoma]]

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <references />

<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.

[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases H]]