Bailey.Glen: Created page with "32.6%{{Under Construction}} ==Primary Author(s)*== Rachel D. Burnside, PhD, MBA, FACMGG TOC ==Cancer Category/Type== Mature B-cell neoplasm ==Cancer Sub-Classificatio..."

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Created page with "32.6%{{Under Construction}} ==Primary Author(s)*== Rachel D. Burnside, PhD, MBA, FACMGG __TOC__ ==Cancer Category/Type== Mature B-cell neoplasm ==Cancer Sub-Classificatio..."

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==Primary Author(s)*==

Rachel D. Burnside, PhD, MBA, FACMGG

__TOC__

==Cancer Category/Type==

Mature B-cell neoplasm

==Cancer Sub-Classification / Subtype==

''In situ'' follicular B-cell neoplasm (ISFN)

==Definition / Description of Disease==

''In situ'' FL is a proliferation of abnormal B-cells within the germinal center or follicles of secondary lymphoid tissues. The neoplastic cells do not infiltrate beyond the follicular dendritic cell barrier and remain confined to the follicles.

==Synonyms / Terminology==

Intrafollicular neoplasia, ''in situ'' follicular neoplasia (ISFN), FL ''in situ'' (FLIS), lymphoma-like B-cells of uncertain/undetermined significance, FL B-cells of undetermined significance, ''in situ'' localization of FL, incipient FL, FL of compartmentalized follicular center cells<ref>{{Cite journal|last=Carbone|first=Antonino|last2=Gloghini|first2=Annunziata|date=2014-03|title=Emerging issues after the recognition of in situ follicular lymphoma|url=http://www.tandfonline.com/doi/full/10.3109/10428194.2013.807926|journal=Leukemia & Lymphoma|language=en|volume=55|issue=3|pages=482–490|doi=10.3109/10428194.2013.807926|issn=1042-8194}}</ref>

==Epidemiology / Prevalence==

The prevalence of in situ FL is unknown but is found in 2-3% of reactive lymph nodes. Fewer than 5% of cases progress to overt FL.<ref>{{Cite journal|last=Tamber|first=Gurdip S|last2=Chévarie‐Davis|first2=Myriam|last3=Warner|first3=Margaret|last4=Séguin|first4=Chantal|last5=Caron|first5=Carole|last6=Michel|first6=René P|date=2021-12|title=In‐situ follicular neoplasia: a clinicopathological spectrum|url=https://onlinelibrary.wiley.com/doi/10.1111/his.14535|journal=Histopathology|language=en|volume=79|issue=6|pages=1072–1086|doi=10.1111/his.14535|issn=0309-0167}}</ref>

==Clinical Features==

Put your text here and fill in the table
{| 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)
|}

==Sites of Involvement==

Abnormal B-cells are confined to the germinal centers in otherwise reactive lymph nodes and do not infiltrate the interfollucular regions.

==Morphologic Features==

Morphology is insufficient to diagnose ''in situ'' FL; immunhistochemistry and genetic testing for t(14;18) are necessary. GCs show monotonous morphology and lack tingible body macrophages. By IHC, cells show strong and uniform staining for BCL2 and CD10 and a low Ki67 index.<ref>{{Cite journal|last=Vogelsberg|first=Antonio|last2=Steinhilber|first2=Julia|last3=Mankel|first3=Barbara|last4=Federmann|first4=Birgit|last5=Schmidt|first5=Janine|last6=Montes-Mojarro|first6=Ivonne A.|last7=Hüttl|first7=Katrin|last8=Rodriguez-Pinilla|first8=Maria|last9=Baskaran|first9=Praveen|date=2021|title=Genetic evolution of in situ follicular neoplasia to aggressive B-cell lymphoma of germinal center subtype|url=https://haematologica.org/article/view/9914|journal=Haematologica|language=en|volume=106|issue=10|pages=2673–2681|doi=10.3324/haematol.2020.254854|issn=1592-8721|pmc=PMC8485666|pmid=32855278}}</ref>

The following description of ISFN is derived from Jegalian et al<ref>{{Cite journal|url=https://ashpublications.org/blood/article/118/11/2976/28482/Follicular-lymphoma-in-situ-clinical-implications|doi=10.1182/blood-2011-05-355255|pmc=PMC3175777|pmid=21768298}}</ref>:

*Unlike early-stage or partial involvement of FL, ''in situ'' FL retains follicular architecture with normal-sized follicles;
*Involved follicles are dispersed throughout the lymph node, as opposed to being clustered together;
*There is an intact cuff with distinct edges to the GC;
*Very strong and uniform expression of BCL2 and CD10 within the follicle;
*Atypical cells are confined to the GC and are almost completely [https://www.sciencedirect.com/topics/immunology-and-microbiology/centrocyte centrocytes] (B-cells which have undergone somatic hypermutation of the B-cell receptor but not yet undergone anitbody affinity maturation)

<br />

==Immunophenotype==

Low Ki67 index

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||BCL2+ (strong)
|-
|Positive (universal)||CD10+ (strong)
|-
|Negative (universal)||IGD-
|-
|Negative (universal)||CD3-
|}

==Chromosomal Rearrangements (Gene Fusions)==

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{| 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
|-
|t(14;18)(q32;q21) or rarely, t(2;18)(p11;q21) or t(18;22)(q21;q11.2)||5' BCL2/3' IGH||der(18)||80-90% of all FL
|Yes, but not restricted to FL; may also be seen in DLBCL
|No
|No
|The translocation results in the juxtaposition of the BCL2 major or minor breakpoint cluster with the VDJ region of IGH during erroneous VDJ recombination<ref>{{Cite journal|url=https://ashpublications.org/blood/article/118/11/2976/28482/Follicular-lymphoma-in-situ-clinical-implications|doi=10.1182/blood-2011-05-355255|pmc=PMC3175777|pmid=21768298}}</ref><ref>{{Cite journal|last=Sotomayor|first=Edgar A.|last2=Shah|first2=Inangati M.|last3=Sanger|first3=Warren G.|last4=Mark|first4=Hon Fong L.|date=2007-10-01|title=In situ follicular lymphoma with a 14;18 translocation diagnosed by a multimodal approach|url=https://www.sciencedirect.com/science/article/pii/S001448000700038X|journal=Experimental and Molecular Pathology|volume=83|issue=2|pages=254–258|doi=10.1016/j.yexmp.2007.03.001|issn=0014-4800}}</ref>
|}

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

Put your text here and fill in the table

{| 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).
|}
==Characteristic Chromosomal Patterns==

Put your text here

{| 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).
|}
==Gene Mutations (SNV/INDEL)==

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{| 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
|-
|'''''CREBBP''''' inactivating missense variants (various); mutation hotspots in exons 24-28 and exon 30.
|TSG
|32.6%<ref name=":0">{{Cite journal|last=Pasqualucci|first=Laura|last2=Dominguez-Sola|first2=David|last3=Chiarenza|first3=Annalisa|last4=Fabbri|first4=Giulia|last5=Grunn|first5=Adina|last6=Trifonov|first6=Vladimir|last7=Kasper|first7=Lawryn H.|last8=Lerach|first8=Stephanie|last9=Tang|first9=Hongyan|date=2011-03|title=Inactivating mutations of acetyltransferase genes in B-cell lymphoma|url=https://www.nature.com/articles/nature09730|journal=Nature|language=en|volume=471|issue=7337|pages=189–195|doi=10.1038/nature09730|issn=1476-4687}}</ref>
|
|
|
|
|
|Inactivating mutations prevent acetylation of the protein and creates an environment permissive for accumulation of mutations<ref>{{Cite journal|last=Schmidt|first=Janine|last2=Ramis-Zaldivar|first2=Joan Enric|last3=Bonzheim|first3=Irina|last4=Steinhilber|first4=Julia|last5=Müller|first5=Inga|last6=Haake|first6=Andrea|last7=Yu|first7=Shan Chi|last8=Raffeld|first8=Mark|last9=Fend|first9=Falko|date=2018-12-20|title=CREBBP gene mutations are frequently detected in in situ follicular neoplasia|url=https://www.sciencedirect.com/science/article/pii/S0006497120429210|journal=Blood|volume=132|issue=25|pages=2687–2690|doi=10.1182/blood-2018-03-837039|issn=0006-4971}}</ref>. Mutations in ''CREBBP'' are thought to be early driver mutations and possibly necessary for transformation to FL, as they have been found in ISFN and paired FL samples<ref>{{Cite journal|last=Schmidt|first=Janine|last2=Ramis-Zaldivar|first2=Joan Enric|last3=Bonzheim|first3=Irina|last4=Steinhilber|first4=Julia|last5=Müller|first5=Inga|last6=Haake|first6=Andrea|last7=Yu|first7=Shan Chi|last8=Raffeld|first8=Mark|last9=Fend|first9=Falko|date=2018-12-20|title=CREBBP gene mutations are frequently detected in in situ follicular neoplasia|url=https://www.sciencedirect.com/science/article/pii/S0006497120429210|journal=Blood|volume=132|issue=25|pages=2687–2690|doi=10.1182/blood-2018-03-837039|issn=0006-4971}}</ref>.
<br />
|-
|'''''EZH2'''''
p.Y646, p.A682G, p.A692V
Gain of function variants. Y646 may have multiple amino acid replacements
|
|8.7%<ref name=":0" />
|
|
|
|
|
|
|}
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.

==Epigenomic Alterations==

Put your text here

==Genes and Main Pathways Involved==

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{| 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
|}
==Genetic Diagnostic Testing Methods==

Put your text here

==Familial Forms==

Put your text here

==Additional Information==

Put your text here

==Links==

Put your text placeholder here (use "Link" icon at top of page)

==References==
<references />
(use "Cite" icon at top of page)
===EXAMPLE Book===

#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p129-171.

==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.

HAEM4Backup:In Situ Follicular Neoplasia - Revision history

Bailey.Glen: Created page with "32.6%{{Under Construction}} ==Primary Author(s)*== Rachel D. Burnside, PhD, MBA, FACMGG __TOC__ ==Cancer Category/Type== Mature B-cell neoplasm ==Cancer Sub-Classificatio..."

Bailey.Glen: Created page with "32.6%{{Under Construction}} ==Primary Author(s)*== Rachel D. Burnside, PhD, MBA, FACMGG TOC ==Cancer Category/Type== Mature B-cell neoplasm ==Cancer Sub-Classificatio..."