In situ follicular B-cell neoplasm

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Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-11-30. The original page can be found at HAEM4:In Situ Follicular Neoplasia.

Primary Author(s)*

Rachel D. Burnside, PhD, MBA, FACMGG

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[1]

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.[2]

Clinical Features

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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.[3]

The following description of ISFN is derived from Jegalian et al[4]:

  • 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 centrocytes (B-cells which have undergone somatic hypermutation of the B-cell receptor but not yet undergone anitbody affinity maturation)


Immunophenotype

Low Ki67 index

Finding Marker
Positive (universal) BCL2+ (strong)
Positive (universal) CD10+ (strong)
Negative (universal) IGD-
Negative (universal) CD3-

Chromosomal Rearrangements (Gene Fusions)

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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[5][6]

Individual Region Genomic Gain / Loss / LOH

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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 (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)

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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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%[7] Inactivating mutations prevent acetylation of the protein and creates an environment permissive for accumulation of mutations[8]. 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[9].


EZH2

p.Y646, p.A682G, p.A692V Gain of function variants. Y646 may have multiple amino acid replacements

8.7%[7]

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

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Genes and Main Pathways Involved

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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

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Additional Information

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Links

Put your text placeholder here (or anywhere appropriate on the page) and use the "Link" icon at the top of the page (Instructions: Once you have a text placeholder entered to which you want to add a link, highlight that text, select the "Link" icon at the top of the page, and search the name of the internal page to which you want to link this text, or enter an external internet address including the "http://www." portion.)

References

  1. Carbone, Antonino; et al. (2014-03). "Emerging issues after the recognition of in situ follicular lymphoma". Leukemia & Lymphoma. 55 (3): 482–490. doi:10.3109/10428194.2013.807926. ISSN 1042-8194. Check date values in: |date= (help)
  2. Tamber, Gurdip S; et al. (2021-12). "In‐situ follicular neoplasia: a clinicopathological spectrum". Histopathology. 79 (6): 1072–1086. doi:10.1111/his.14535. ISSN 0309-0167. Check date values in: |date= (help)
  3. Vogelsberg, Antonio; et al. (2021). "Genetic evolution of in situ follicular neoplasia to aggressive B-cell lymphoma of germinal center subtype". Haematologica. 106 (10): 2673–2681. doi:10.3324/haematol.2020.254854. ISSN 1592-8721. PMC PMC8485666 Check |pmc= value (help). PMID 32855278 Check |pmid= value (help).CS1 maint: PMC format (link)
  4. . doi:10.1182/blood-2011-05-355255. PMC 3175777. PMID 21768298 https://ashpublications.org/blood/article/118/11/2976/28482/Follicular-lymphoma-in-situ-clinical-implications. Missing or empty |title= (help)CS1 maint: PMC format (link)
  5. . doi:10.1182/blood-2011-05-355255. PMC 3175777. PMID 21768298 https://ashpublications.org/blood/article/118/11/2976/28482/Follicular-lymphoma-in-situ-clinical-implications. Missing or empty |title= (help)CS1 maint: PMC format (link)
  6. Sotomayor, Edgar A.; et al. (2007-10-01). "In situ follicular lymphoma with a 14;18 translocation diagnosed by a multimodal approach". Experimental and Molecular Pathology. 83 (2): 254–258. doi:10.1016/j.yexmp.2007.03.001. ISSN 0014-4800.
  7. 7.0 7.1 Pasqualucci, Laura; et al. (2011-03). "Inactivating mutations of acetyltransferase genes in B-cell lymphoma". Nature. 471 (7337): 189–195. doi:10.1038/nature09730. ISSN 1476-4687. Check date values in: |date= (help)
  8. Schmidt, Janine; et al. (2018-12-20). "CREBBP gene mutations are frequently detected in in situ follicular neoplasia". Blood. 132 (25): 2687–2690. doi:10.1182/blood-2018-03-837039. ISSN 0006-4971.
  9. Schmidt, Janine; et al. (2018-12-20). "CREBBP gene mutations are frequently detected in in situ follicular neoplasia". Blood. 132 (25): 2687–2690. doi:10.1182/blood-2018-03-837039. ISSN 0006-4971.

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Notes

*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.


*Citation of this Page: “In situ follicular B-cell neoplasm”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/30/2023, https://ccga.io/index.php/HAEM5:In_situ_follicular_B-cell_neoplasm.