Bailey.Glen at 21:35, 4 December 2023

2023-12-04T21:35:29Z

← Older revision		Revision as of 16:35, 4 December 2023
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	==Links==		==Links==

	[[~~Testicular~~ Follicular ~~Lymphoma~~]]		[[HAEM5:Follicular lymphoma]]

	[[In ~~Situ Follicular Neoplasia~~]]		[[HAEM5:In situ follicular B-cell neoplasm]]

	[[Duodenal-~~Type Follicular Lymphoma~~]]		[[HAEM5:Duodenal-type follicular lymphoma]]

	[Https://progenetix.org/subsets/list%3Ffilters%3DNCIT:C3209%26datasetIds%3Dprogenetix Progenetix.org Follicular Lymphoma CNV plot] your links here (use "Link" icon at top of page)		[Https://progenetix.org/subsets/list%3Ffilters%3DNCIT:C3209%26datasetIds%3Dprogenetix Progenetix.org Follicular Lymphoma CNV plot] your links here (use "Link" icon at top of page)

Bailey.Glen at 18:52, 3 November 2023

2023-11-03T18:52:10Z

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 {{Under Construction}}
 ==Primary Author(s)*==
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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.

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital Rachel D. Burnside, PhD, MBA, FACMG, University of Florida TOC =..."

2023-11-03T18:14:30Z

Created page with "{{Under Construction}} ==Primary Author(s)*== Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital Rachel D. Burnside, PhD, MBA, FACMG, University of Florida __TOC__ =..."

New page

{{Under Construction}}
==Primary Author(s)*==

Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital

Rachel D. Burnside, PhD, MBA, FACMG, University of Florida

__TOC__

==Cancer Category/Type==

Mature B Cell Neoplasm

==Cancer Sub-Classification / Subtype==

Follicular Lymphoma

==Definition / Description of Disease==

*Follicular Lymphoma (FL) arises from germinal center B cells of the secondary lymphatic system (lymph nodes, spleen)
*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 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>
*For most patients, FL is a chronic, incurable disease with survival often measured in decades.
*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 [1, 2, 3, 4]==

*FL commonly presents as painless lymphadenopathy<ref name=":1" />
*May wax and wane over years before diagnosis
*Majority of cases have widespread involvement at diagnosis<ref name=":1" />
*Bone marrow involvement in 40-70% of cases at diagnosis
*May not require treatment depending staging and other parameters.

==Sites of Involvement [1, 2, 3, 4]==

Lymph Nodes / Lymphadenopathy; Spleen; Bone Marrow

==Morphologic Features [1, 2, 3, 4]==

Appearance of predominantly follicular pattern

Consists of both centrocytes and centroblasts, with the relative proportions of these cells informing grading

Grade I: 0-5 centroblasts/high power field (hpf)

Grade II: 6-15 centroblasts/hpf

Grade III: >15 centroblasts/hpf

Grade IIIa: centrocytes present

Grade IIIb: sheets of centroblasts

==Immunophenotype [1, 9, 10]==

Typical FL has CD10+, BL2+. Atypical FL subgroups CD10- and/or BCL2 - all FL are STMN+ - useful differentiator between atypical FL and MZL [9]

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||monotypic surface Ig (sIg)+, BCL2, CD10, CD19, CD20, CD79a, STMN+
|-
|Positive (subset)||atypical FL [CD10+/- and/or BCL2 +/-]
|-
|Negative (universal)||CD5-, CD23-, CD43-
|-
|Negative (subset)||
|}

==Chromosomal Rearrangements (Gene Fusions) [1, 2, 5, 7, 9, 11]==

BCL2 and BCL6 rearrangements appear mutually exclusive [9]

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
|-
|t(14;18)(q32;q21)
|''IGH-BCL2''
|der(14)||85-90%
|-
|t(3;14)(q27;q32)||''BCL6-IGH''||der(3)||10-15%
|}

==Characteristic Chromosomal Aberrations / Patterns [11]==

Put your text here

==Genomic Gain/Loss/LOH==

deletions in 1p36, 6q, 10q, 13p, 17p; gains of 1q, 2p, 7, 8, 12q, 18q
==Gene Mutations (SNV/INDEL)==

Put your text here and/or fill in the tables

{| class="wikitable sortable"
|-
!Gene!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|''KMT2D''|| ||epigenetic modification||EXAMPLE LOF||70-80%
|-
|''CREBBP''
|
|epigenetic modification
|
|70%
|-
|''EP300''
|
|epigenetic modification
|
|15%
|-
|''TNFRSF14''
|
|epigenetic modification
|
|40%
|-
|Histone H1, H2B families
|
|epigenetic modification
|
|
|}

===Other Mutations===
{| class="wikitable sortable"
|-
!Type!!Gene/Region/Other
|-
|Concomitant Mutations||EXAMPLE IDH1 R123H
|-
|Secondary Mutations||EXAMPLE Trisomy 7
|-
|Mutually Exclusive||BCL2, BCL6 rearrangement
|}

==Epigenomics (Methylation)==

''KMT2D,'' H3K4 methyltransferase, ''CREBBP'' Histone acetyltransferase (HAT) enzyme, and ''EZH2'' SET domain histone methyltransferase mutations

==Genes and Main Pathways Involved==

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

==Diagnostic Testing Methods==

Surgical excision preferred; FISH or PCR for ''BCL2'' rearrangement; preserve frozen tissue for further molecular testing

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

Most common: Risk stratification using Follicular Lymphoma International Prognostic Index (FLIPI) is based on clinical indicators.

(m7-FLIPI adds performance status plus mutational status of ''EZH2'', ''ARID1A'', ''MEF2B'', ''EP300'', ''FOXO1'', ''CREBBP'' and ''CARD11'' - utility not confirmed [7])

==Familial Forms==

SNPs within HLA class I or II genes [8] or homozygosity of HLA class II genes [9]

==Other Information==
Progenetix.org Follicular Lymphoma CNV plot: <nowiki>https://progenetix.org/subsets/list?filters=NCIT:C3209&datasetIds=progenetix</nowiki>

Precursor B cells typically mature in the marrow, where they may become mature naïve B cells or may apoptose. Following antigen exposure, mature B cells may become short lived plasma cells, or may enter the germinal center and undergo somatic hypermutation and heavy chain class switching.

==Links==

[[Testicular Follicular Lymphoma]]

[[In Situ Follicular Neoplasia]]

[[Duodenal-Type Follicular Lymphoma]]

[Https://progenetix.org/subsets/list%3Ffilters%3DNCIT:C3209%26datasetIds%3Dprogenetix Progenetix.org Follicular Lymphoma CNV plot] your links here (use "Link" icon at top of page)

==References==
<references />
(use "Cite" icon at top of page)
<references group="Jaffe ES, et al.,(2017) Follicular Lymphoma, in Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, LeBeau MM, Orazi A, Siebert R. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, IARC, Lyon, p. 266-273" responsive="0" /><ref>{{Cite journal|last=Swerdlow|first=Steven H.|last2=Campo|first2=Elias|last3=Pileri|first3=Stefano A.|last4=Harris|first4=Nancy Lee|last5=Stein|first5=Harald|last6=Siebert|first6=Reiner|last7=Advani|first7=Ranjana|last8=Ghielmini|first8=Michele|last9=Salles|first9=Gilles A.|date=2016-05-19|title=The 2016 revision of the World Health Organization classification of lymphoid neoplasms|url=http://dx.doi.org/10.1182/blood-2016-01-643569|journal=Blood|volume=127|issue=20|pages=2375–2390|doi=10.1182/blood-2016-01-643569|issn=0006-4971}}</ref><ref>{{Cite journal|last=Cerhan|first=James R.|date=08 2020|title=Epidemiology of Follicular Lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/32586570|journal=Hematology/Oncology Clinics of North America|volume=34|issue=4|pages=631–646|doi=10.1016/j.hoc.2020.02.001|issn=1558-1977|pmc=7323888|pmid=32586570}}</ref><ref>{{Cite journal|last=Odutola|first=Michael K.|last2=Nnakelu|first2=Eriobu|last3=Giles|first3=Graham G.|last4=van Leeuwen|first4=Marina T.|last5=Vajdic|first5=Claire M.|date=2020-11|title=Lifestyle and risk of follicular lymphoma: a systematic review and meta-analysis of observational studies|url=https://pubmed.ncbi.nlm.nih.gov/32851495|journal=Cancer causes & control: CCC|volume=31|issue=11|pages=979–1000|doi=10.1007/s10552-020-01342-9|issn=1573-7225|pmid=32851495}}</ref><ref>{{Cite journal|last=Pickard|first=Lucy|last2=Palladino|first2=Giuseppe|last3=Okosun|first3=Jessica|date=10 2020|title=Follicular lymphoma genomics|url=https://pubmed.ncbi.nlm.nih.gov/32427008|journal=Leukemia & Lymphoma|volume=61|issue=10|pages=2313–2323|doi=10.1080/10428194.2020.1762883|issn=1029-2403|pmid=32427008}}</ref><ref>{{Cite journal|last=Krysiak|first=Kilannin|last2=Gomez|first2=Felicia|last3=White|first3=Brian S.|last4=Matlock|first4=Matthew|last5=Miller|first5=Christopher A.|last6=Trani|first6=Lee|last7=Fronick|first7=Catrina C.|last8=Fulton|first8=Robert S.|last9=Kreisel|first9=Friederike|date=01 26, 2017|title=Recurrent somatic mutations affecting B-cell receptor signaling pathway genes in follicular lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/28064239|journal=Blood|volume=129|issue=4|pages=473–483|doi=10.1182/blood-2016-07-729954|issn=1528-0020|pmc=5270390|pmid=28064239}}</ref><ref>{{Cite journal|last=Dreyling|first=M.|last2=Ghielmini|first2=M.|last3=Rule|first3=S.|last4=Salles|first4=G.|last5=Vitolo|first5=U.|last6=Ladetto|first6=M.|last7=ESMO Guidelines Committee|date=12 01, 2017|title=Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up|url=https://pubmed.ncbi.nlm.nih.gov/28327933|journal=Annals of Oncology: Official Journal of the European Society for Medical Oncology|volume=28|issue=12|pages=3109|doi=10.1093/annonc/mdx020|issn=1569-8041|pmid=28327933}}</ref><ref>{{Cite journal|last=McAulay|first=K. A.|last2=Jarrett|first2=R. F.|date=2015-08|title=Human leukocyte antigens and genetic susceptibility to lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26189878|journal=Tissue Antigens|volume=86|issue=2|pages=98–113|doi=10.1111/tan.12604|issn=1399-0039|pmid=26189878}}</ref><ref>{{Cite journal|last=Wang|first=Sophia S.|last2=Carrington|first2=Mary|last3=Berndt|first3=Sonja I.|last4=Slager|first4=Susan L.|last5=Bracci|first5=Paige M.|last6=Voutsinas|first6=Jenna|last7=Cerhan|first7=James R.|last8=Smedby|first8=Karin E.|last9=Hjalgrim|first9=Henrik|date=07 15, 2018|title=HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes|url=https://pubmed.ncbi.nlm.nih.gov/29735552|journal=Cancer Research|volume=78|issue=14|pages=4086–4096|doi=10.1158/0008-5472.CAN-17-2900|issn=1538-7445|pmc=6065509|pmid=29735552}}</ref><ref>{{Cite journal|last=Marafioti|first=Teresa|last2=Copie-Bergman|first2=Christiane|last3=Calaminici|first3=Maria|last4=Paterson|first4=Jennifer C.|last5=Shende|first5=Vishvesh H.|last6=Liu|first6=Hongxiang|last7=Baia|first7=Maryse|last8=Ramsay|first8=Alan D.|last9=Agostinelli|first9=Claudio|date=2013-05|title=Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups|url=https://pubmed.ncbi.nlm.nih.gov/23509938|journal=Histopathology|volume=62|issue=6|pages=860–875|doi=10.1111/his.12076|issn=1365-2559|pmid=23509938}}</ref>

==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.

HAEM4:Follicular Lymphoma - Revision history

Bailey.Glen at 21:35, 4 December 2023

Bailey.Glen at 18:52, 3 November 2023

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital Rachel D. Burnside, PhD, MBA, FACMG, University of Florida __TOC__ =..."

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital Rachel D. Burnside, PhD, MBA, FACMG, University of Florida TOC =..."