View source for HAEM5:Diffuse large B-cell lymphoma, NOS

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

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<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Diffuse Large B-cell Lymphoma, Not Otherwise Specified]].
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<span style="color:#0070C0">(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use [https://www.genenames.org/ <u>HUGO-approved gene names and symbols</u>] (italicized when appropriate), [https://varnomen.hgvs.org/ HGVS-based nomenclature for variants], as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples). Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see </span><u>[[Author_Instructions]]</u><span style="color:#0070C0"> and [[Frequently Asked Questions (FAQs)|<u>FAQs</u>]] as well as contact your [[Leadership|<u>Associate Editor</u>]] or [mailto:CCGA@cancergenomics.org <u>Technical Support</u>])</span>

==Primary Author(s)*==

Ashwini Yenamandra, PhD FACMG, Vanderbilt University Medical Center

__TOC__

==Cancer Category / Type==

Diffuse Large B-Cell Lymphoma (DLBCL): Not Otherwise Specified (NOS)

==Cancer Sub-Classification / Subtype==

Not Otherwise Specified (NOS)

==Definition / Description of Disease==

Non-Hodgkin lymphoma (NHL) is one of the most frequently diagnosed cancer types representing approximately 4% of cancers Worldwide. The most common type of NHL is Diffuse Large B-Cell Lymphoma, Not Otherwise Specified (DLBCL, NOS) accounting for 30% of all NHL cases. 
==Synonyms / Terminology==

DLBCL, NOS

==Epidemiology / Prevalence==

DLBCL, NOS constitutes close to 30% of NHL. It is more common in the elderly with an average age of 60 years, but it is also seen in all age groups. Put your text here

==Clinical Features==

Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)

EXAMPLE B-symptoms (weight loss, fever, night sweats)

EXAMPLE Fatigue

EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias

EXAMPLE Lymphocytosis (low level)
|}


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

The primary site of lymphoma, either the lymph node or extra nodal site, is important in assessing clinical features, treatment options and outcome of the disease. Clinical presentation of DLBCL can be variable, usually depends on the site of disease involvement, rapid growth rate, enlarged lymph nodes, extra nodal mass infiltrating into tissues or obstructing organs. The enlarged lymphomatous mass may also exert severe pain. Patients usually experience fever, drenching night sweats, weight loss, anorexia, pedal edema (due to extensive pelvic lymphadenopathy), fatigue, chest discomfort or shortness of breath due to mediastinal lymphadenopathy. Put your text here

</blockquote>
==Sites of Involvement==

Lymph node or extra nodal site, enlarged lymph nodes, extra nodal mass infiltrating into tissues or obstructing organs. The enlarged lymphomatous mass may also exert severe pain. 

==Morphologic Features==

Clinical presentation of DLBCL can be variable, usually depends on the site of disease involvement, rapid growth rate, enlarged lymph nodes, extra nodal mass infiltrating into tissues or obstructing organs. The enlarged lymphoma mass may also exert severe pain. Patients usually experience fever, drenching night sweats, weight loss, anorexia, pedal edema (due to extensive pelvic lymphadenopathy), fatigue, chest discomfort or shortness of breath due to mediastinal lymphadenopathy.

==Immunophenotype==

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

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||EXAMPLE CD1
|-
|Positive (subset)||EXAMPLE CD2
|-
|Negative (universal)||EXAMPLE CD3
|-
|Negative (subset)||EXAMPLE CD4
|}

==Chromosomal Rearrangements (Gene Fusions)==

Put your text here and fill in the table

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE

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).
|}		
			


<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}

'''Prognosis:'''  Diagnosis this disease may allow appropriate prophylactic measures, including H1 and H2 blockers, proton pump inhibitors and steroids, to be initiated to minimize its protean complications.


'''Therapeutic Implications:''' 

</blockquote>
==Individual Region Genomic Gain / Loss / LOH==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>

{| class="wikitable sortable"
|-
!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

7
|EXAMPLE Loss
|EXAMPLE

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

chr7
|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

8
|EXAMPLE Gain
|EXAMPLE

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

chr8
|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.}}

'''AMPLIFICATION''': BCL2, REL, CD274, PDCD1LG2, JAK2, KRAs, TBL1XR1, RB1

'''DELETION''': CDKN2A, TNFAIP3, CDKN2B, TNFRSF14, CD70, CD58, PTEN
{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
|-
|EXAMPLE 8||EXAMPLE Gain||EXAMPLE chr8:0-1000000
|-
|EXAMPLE 7||EXAMPLE Loss||EXAMPLE chr7:0-1000000
|}	
		
</blockquote>
==Characteristic Chromosomal Patterns==

Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>

{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE

Co-deletion of 1p and 18q
|Yes
|No
|No
|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.}}

Due to the clinicopathologic, biological and genetic diversity, DLBCL is sub divided into morphological variants and molecular subtypes. Initial workup and evaluation of DLBCL has become increasingly complex partly due to the genetic abnormalities that are targets for specific therapy and play an important role in monitoring residual disease. Genomic studies help in clinical management, risk stratification, enrolling patients onto treatment protocols, clinical trials, and detection of therapeutic targets. GS, If IHC is positive for GCB like DLBCL, FISH and Cytogenetics for MYC, BCL2 or BCL6 gene rearrangement are recommended to rule out double and triple hit lymphoma. 

</blockquote>
==Gene Mutations (SNV / INDEL)==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>

{| class="wikitable sortable"
|-
!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
|
|
|
|EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
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.}}

'''SNV''' : MLL2, TP53, MYD88, B2M, CREBBP, TNFAIP3, PIM1, BCL2, EZH2, TNFRSF14, CD79B

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|EXAMPLE TP53||EXAMPLE R273H||EXAMPLE Tumor Suppressor||EXAMPLE LOF||EXAMPLE 20%
|}	
		
===Other Mutations===
{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|Mutually Exclusive||EXAMPLE EGFR Amplification
|}

</blockquote>
==Epigenomic Alterations==

Ø  Epigenetic Modification : Recurrent mutations in genes that encode for histone/chromatin modifiers that include methyltransferases, acetyltransferases, and histones.

Ø  Gain of function -EZH2-mutations in 22% GCB

Ø  Loss of Functiom-MLL2(KMT2D, methyl transferase, truncating)/MLL3 -mutations-35% in GCB and ABC

Ø  Loss of unction F-CREBBP(25%)/EP300 (5%)-inactivation of the acetyltransferase genes, mutations, and deletions, 30% in GCB and 15% in ABC

==Genes and Main Pathways Involved==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|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.}}

B-Cell differentiation, TP53 pathway, NF-kB pathway, Apoptosis, Cell migration, Immune response,BCR-MYD88 signaling, PI3K-AKT-mTCR pathway

</blockquote>
==Genetic Diagnostic Testing Methods==

NGS, If IHC is positive for GCB like DLBCL, FISH and Cytogenetics for MYC, BCL2 or BCL6 gene rearrangement are recommended to rule out double and triple hit lymphoma.

==Familial Forms==

Not Available

==Additional Information==

Not Available

==Links==

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==References==
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'''

==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.
<nowiki>*</nowiki>''Citation of this Page'': “Diffuse large B-cell lymphoma, NOS”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Diffuse_large_B-cell_lymphoma,_NOS</nowiki>.
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