HAEM5:In situ follicular B-cell neoplasm: Difference between revisions

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|Subtype(s)
|Subtype(s)
|In situ follicular B-cell neoplasm
|In situ follicular B-cell neoplasm
|}
==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 <span style="color:#0070C0">(''Instruction: Can include references in the table. Do not delete table.'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|<span class="blue-text">EXAMPLE:</span> Asymptomatic (incidental finding on complete blood counts)
<span class="blue-text">EXAMPLE:</span> B-symptoms (weight loss, fever, night sweats)
<span class="blue-text">EXAMPLE:</span> Fatigue
<span class="blue-text">EXAMPLE:</span> Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|<span class="blue-text">EXAMPLE:</span> Cytopenias
<span class="blue-text">EXAMPLE:</span> 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 name=":1">{{Cite journal|last=Jegalian|first=Armin G.|last2=Eberle|first2=Franziska C.|last3=Pack|first3=Svetlana D.|last4=Mirvis|first4=Mariya|last5=Raffeld|first5=Mark|last6=Pittaluga|first6=Stefania|last7=Jaffe|first7=Elaine S.|date=2011-09-15|title=Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21768298|journal=Blood|volume=118|issue=11|pages=2976–2984|doi=10.1182/blood-2011-05-355255|issn=1528-0020|pmc=3175777|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-
|}
|}


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|No
|No
|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 name=":1" /><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>
|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 name=":1">{{Cite journal|last=Jegalian|first=Armin G.|last2=Eberle|first2=Franziska C.|last3=Pack|first3=Svetlana D.|last4=Mirvis|first4=Mariya|last5=Raffeld|first5=Mark|last6=Pittaluga|first6=Stefania|last7=Jaffe|first7=Elaine S.|date=2011-09-15|title=Follicular lymphoma in situ: clinical implications and comparisons with partial involvement by follicular lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/21768298|journal=Blood|volume=118|issue=11|pages=2976–2984|doi=10.1182/blood-2011-05-355255|issn=1528-0020|pmc=3175777|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>
|}
|}


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==Additional Information==
==Additional Information==


Put your text here
This disease is <u>defined/characterized</u> as detailed below:
 
* ''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.<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>
 
The <u>epidemiology/prevalence</u> of this disease is detailed below:
 
* 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>
 
The <u>sites of involvement</u> of this disease are detailed below:
 
* Abnormal B-cells are confined to the germinal centers in otherwise reactive lymph nodes and do not infiltrate the interfollucular regions.
 
The <u>morphologic features</u> of this disease are detailed below:
 
* 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 name=":1" />:
**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)
 
The <u>immunophenotype</u> of this disease is detailed below:
 
* Low Ki67 index
 
* Positive (universal) - BCL2+ (strong), CD10+ (strong)
 
* Negative (universal) - IGD-, CD3-


==Links==
==Links==