Compendium of Cancer Genome Aberrations

HAEM5:Follicular lymphoma: Difference between revisions

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<blockquote class='blockedit'>{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Follicular Lymphoma]].
<blockquote class="blockedit">{{Box-round|title=Content Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification|This page was converted to the new template on 2023-12-07. The original page can be found at [[HAEM4:Follicular Lymphoma]].
Other relevent pages include: [[HAEM4:Testicular Follicular Lymphoma]]
Other relevent pages include: [[HAEM4:Testicular Follicular Lymphoma]]


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Rachel D. Burnside, PhD, MBA, FACMG, University of Florida
Rachel D. Burnside, PhD, MBA, FACMG, University of Florida
__TOC__
==WHO Classification of Disease==
==WHO Classification of Disease==


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|Follicular lymphoma
|Follicular lymphoma
|}
|}
==Related Terminology==


==Definition / Description of Disease==
{| class="wikitable"
 
|+
*Follicular Lymphoma (FL) arises from germinal center B cells of the secondary lymphatic system (lymph nodes, spleen)
|Acceptable
*WHO 5th edition classifies FL into four variants:  ''in situ'' FL, duodenal-type FL, pediatric FL, and Follicular Lymphoma<ref name=":0">{{Cite journal|last=Alaggio|first=Rita|last2=Amador|first2=Catalina|last3=Anagnostopoulos|first3=Ioannis|last4=Attygalle|first4=Ayoma D.|last5=Araujo|first5=Iguaracyra Barreto de Oliveira|last6=Berti|first6=Emilio|last7=Bhagat|first7=Govind|last8=Borges|first8=Anita Maria|last9=Boyer|first9=Daniel|date=2022|title=The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9214472/|journal=Leukemia|volume=36|issue=7|pages=1720–1748|doi=10.1038/s41375-022-01620-2|issn=0887-6924|pmc=9214472|pmid=35732829}}</ref>.
|FL grades 1, 2, 3A, and 3B; BCL2-R–negative CD23-positive follicle centre lymphoma (for some cases of FL with dominant diffuse growth pattern only)
**FL is further classified as Classic FL (cFL), characterized by t(14;18), follicular large B-cell lymphoma (FLBL), and FL with uncommon features (uFL)<ref name=":0" />
|-
**There is emerging evidence that FL may arise from ''in situ'' FL or as a primary <ref>{{Cite journal|last=Carbone|first=Antonino|last2=Gloghini|first2=Annunziata|last3=Santoro|first3=Armando|date=2012-03|title=In situ follicular lymphoma: pathologic characteristics and diagnostic features: In situ follicular lymphoma|url=https://onlinelibrary.wiley.com/doi/10.1002/hon.993|journal=Hematological Oncology|language=en|volume=30|issue=1|pages=1–7|doi=10.1002/hon.993}}</ref>
|Not Recommended
*For most patients, FL is a chronic, incurable disease with survival often measured in decades.
|N/A
*Histologic transformation to more aggressive disease with potentially fatal outcome may occur
|}
 
==Synonyms / Terminology==
 
Follicular Center Lymphoma; Follicle-related B-cell Lymphoma
 
==Epidemiology / Prevalence==
 
Slight male predominance (male-to-female ratio of 1.2:1)
 
Median age at diagnosis is 60-65 years;
 
Progressive increase in incidence between ages 35-70
 
FL is extremely rare in children; considered a separate entity from adult FL
 
~5% of all hematological neoplasms are FL
 
~20% of all non-Hodgkin lymphomas are FL<ref name=":1">{{Cite journal|last=Ferry|first=Judith A.|date=2010-12-01|title=Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ|url=https://www.sciencedirect.com/science/article/pii/S1875918110001133|journal=Surgical Pathology Clinics|series=Current Concepts in Hematopathology|volume=3|issue=4|pages=877–906|doi=10.1016/j.path.2010.08.002|issn=1875-9181}}</ref>
 
Highest incidence in developed/high income countries
 
Second most common lymphoma in the USA and western Europe
 
Most common lymphoma among non-Hispanic white population [2]
 
Environmental exposures to pesticides and herbicides as risk factors are disputed; Hair dye use prior to 1980 is associated with increased risk (meta RR = 1.66) [3, 4].
 
Genetic risk factors may include SNPs within HLA class I or II genes [8] or homozygosity of HLA class II genes [9]; these features have been identified within a few familial cases of FL.
----
 
==Clinical Features==
 
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
 
*FL commonly presents as painless lymphadenopathy<ref name=":12" />
*May wax and wane over years before diagnosis
*Majority of cases have widespread involvement at diagnosis<ref name=":12" />
*Bone marrow involvement in 40-70% of cases at diagnosis
*May not require treatment depending staging and other parameters.
 
 
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==Sites of Involvement==
 
 
Lymph Nodes / Lymphadenopathy; Spleen; Bone Marrow  
 
 
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</blockquote>
==Morphologic Features==
 
 
Appearance of predominantly follicular pattern
 
Consists of both centrocytes and centroblasts, with the relative proportions of these cells informing grading
 
Grade 1:   0-5 centroblasts/high power field (hpf)
 
Grade 2:  6-15 centroblasts/hpf
 
Grade III: >15 centroblasts/hpf
 
       Grade IIIa:  centrocytes present
 
Grade IIIb:  sheets of centroblasts
 
 
==Immunophenotype==
 
 
Typically, FL is CD10+, BL2+.  Atypical FL subgroups CD10- and/or BCL2 - all FL are STMN+ - useful differentiator between atypical FL and MZL [9]


==Gene Rearrangements==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Finding!!Marker
!Driver Gene!!Fusion(s) and Common Partner Genes!!Molecular Pathogenesis!!Typical Chromosomal Alteration(s)
!Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!Clinical Relevance Details/Other Notes
|-
|-
|Positive (universal)||monotypic surface Ig (sIg)+, BCL2, CD10, CD19, CD20, CD79a, STMN+
|<span class="blue-text">EXAMPLE:</span> ''ABL1''||<span class="blue-text">EXAMPLE:</span> ''BCR::ABL1''||<span class="blue-text">EXAMPLE:</span> The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1.||<span class="blue-text">EXAMPLE:</span> t(9;22)(q34;q11.2)
|<span class="blue-text">EXAMPLE:</span> Common (CML)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|<span class="blue-text">EXAMPLE:</span> Yes (WHO, NCCN)
|<span class="blue-text">EXAMPLE:</span>
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). BCR::ABL1 is generally favorable in CML (add reference).
|-
|-
|Positive (subset)||atypical FL [CD10+/- and/or BCL2 +/-]
|<span class="blue-text">EXAMPLE:</span> ''CIC''
|<span class="blue-text">EXAMPLE:</span> ''CIC::DUX4''
|<span class="blue-text">EXAMPLE:</span> Typically, the last exon of ''CIC'' is fused to ''DUX4''. The fusion breakpoint in ''CIC'' is usually intra-exonic and removes an inhibitory sequence, upregulating ''PEA3'' genes downstream of ''CIC'' including ''ETV1'', ''ETV4'', and ''ETV5''.
|<span class="blue-text">EXAMPLE:</span> t(4;19)(q25;q13)
|<span class="blue-text">EXAMPLE:</span> Common (CIC-rearranged sarcoma)
|<span class="blue-text">EXAMPLE:</span> D
|
|<span class="blue-text">EXAMPLE:</span>
 
''DUX4'' has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references).
|-
|-
|Negative (universal)||CD5-, CD23-, CD43-
|<span class="blue-text">EXAMPLE:</span> ''ALK''
|-
|<span class="blue-text">EXAMPLE:</span> ''ELM4::ALK''
|Negative (subset)||
|}




==WHO Essential and Desirable Genetic Diagnostic Criteria==
Other fusion partners include ''KIF5B, NPM1, STRN, TFG, TPM3, CLTC, KLC1''
<span style="color:#0070C0">(''Instructions: The table will have the diagnostic criteria from the WHO book <u>autocompleted</u>; remove any <u>non</u>-genetics related criteria. If applicable, add text about other classification'' ''systems that define this entity and specify how the genetics-related criteria differ.'')</span>
|<span class="blue-text">EXAMPLE:</span> Fusions result in constitutive activation of the ''ALK'' tyrosine kinase. The most common ''ALK'' fusion is ''EML4::ALK'', with breakpoints in intron 19 of ''ALK''. At the transcript level, a variable (5’) partner gene is fused to 3’ ''ALK'' at exon 20. Rarely, ''ALK'' fusions contain exon 19 due to breakpoints in intron 18.
{| class="wikitable"
|<span class="blue-text">EXAMPLE:</span> N/A
|+
|<span class="blue-text">EXAMPLE:</span> Rare (Lung adenocarcinoma)
|WHO Essential Criteria (Genetics)*
|<span class="blue-text">EXAMPLE:</span> T
|
|
|<span class="blue-text">EXAMPLE:</span>
Both balanced and unbalanced forms are observed by FISH (add references).
|-
|-
|WHO Desirable Criteria (Genetics)*
|<span class="blue-text">EXAMPLE:</span> ''ABL1''
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Intragenic deletion of exons 2–7 in ''EGFR'' removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways.
|<span class="blue-text">EXAMPLE:</span> N/A
|<span class="blue-text">EXAMPLE:</span> Recurrent (IDH-wildtype Glioblastoma)
|<span class="blue-text">EXAMPLE:</span> D, P, T
|
|
|
|-
|-
|Other Classification
|
|
|}
<nowiki>*</nowiki>Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the [https://tumourclassification.iarc.who.int/home <u>WHO Classification of Tumours</u>].
==Related Terminology==
<span style="color:#0070C0">(''Instructions: The table will have the related terminology from the WHO <u>autocompleted</u>.)''</span>
{| class="wikitable"
|+
|Acceptable
|
|
|-
|
|Not Recommended
|
|
|
|
|
|
|}
|}
==Gene Rearrangements==


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


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''
!Chr #!!Gain, Loss, Amp, LOH!!Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]!!Relevant Gene(s)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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|}


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deletions in 1p36, 6q, 10q, 13p, 17p; gains of 1q, 2p, 7, 8, 12q, 18q
deletions in 1p36, 6q, 10q, 13p, 17p; gains of 1q, 2p, 7, 8, 12q, 18q
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!Chromosomal Pattern
!Chromosomal Pattern
!Molecular Pathogenesis
!Molecular Pathogenesis
!'''Prevalence -'''
!Prevalence -  
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>
|<span class="blue-text">EXAMPLE:</span>
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|}
|}


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{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''
!Gene!!Genetic Alteration!!Tumor Suppressor Gene, Oncogene, Other!!Prevalence -
'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''
Common >20%, Recurrent 5-20% or Rare <5% (Disease)
!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''
!Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  
!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''
!Established Clinical Significance Per Guidelines - Yes or No (Source)
!'''Clinical Relevance Details/Other Notes'''
!Clinical Relevance Details/Other Notes
|-
|-
|<span class="blue-text">EXAMPLE:</span>''EGFR''
|<span class="blue-text">EXAMPLE:</span>''EGFR''
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|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.


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''BCR-NFκB'', ''JAK/STAT''; ''mTORC'' signaling
''BCR-NFκB'', ''JAK/STAT''; ''mTORC'' signaling
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