HAEM5:Follicular lymphoma
Haematolymphoid Tumours (WHO Classification, 5th ed.)
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editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition ClassificationThis 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
Note: autho needs to correlate with Testicular Follicular Lymphoma
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Primary Author(s)*
Ruthann Pfau, PhD, FACMG, Nationwide Children's Hospital
Rachel D. Burnside, PhD, MBA, FACMG, University of Florida
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | B-cell lymphoid proliferations and lymphomas |
| Family | Mature B-cell neoplasms |
| Type | N/A |
| Subtype(s) | 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[1].
- 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[3]
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
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- FL commonly presents as painless lymphadenopathy[4]
- May wax and wane over years before diagnosis
- Majority of cases have widespread involvement at diagnosis[4]
- Bone marrow involvement in 40-70% of cases at diagnosis
- May not require treatment depending staging and other parameters.
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editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.[1, 2, 3, 4]
Sites of Involvement
Lymph Nodes / Lymphadenopathy; Spleen; Bone Marrow
editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.[1, 2, 3, 4]
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]
| 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)
| 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) | 5' IGH / 3' BCL2 | der(18) | 80%~90% | No | No | No | Rarely, BCL2 rearrangement may also be observed with IGK at 2p11.2 or IGL at 22q11.22. Additional info and example karyotypes can be found here. |
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.
BCL2 and BCL6 rearrangements appear mutually exclusive [9]
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%
editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.[1, 2, 5, 7, 9, 11]
editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).Please incorporate this section into the relevant tables found in:
- Chromosomal Rearrangements (Gene Fusions)
- Individual Region Genomic Gain/Loss/LOH
- Characteristic Chromosomal Patterns
- Gene Mutations (SNV/INDEL)
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])
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). |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.deletions in 1p36, 6q, 10q, 13p, 17p; gains of 1q, 2p, 7, 8, 12q, 18q
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. Do not delete table.)
| 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). |
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
Put your text here
editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.[11]
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 |
|---|---|---|---|---|---|---|---|---|
| EXAMPLE: TP53; Variable LOF mutations
EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations |
EXAMPLE: TSG | EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference) |
EXAMPLE: IDH1 R123H | EXAMPLE: EGFR amplification | EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
|
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.
editv4:Gene Mutations (SNV/INDEL)The content below was from the old template. Please incorporate above.Put your text here and/or fill in the tables
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
Type Gene/Region/Other Concomitant Mutations EXAMPLE: IDH1 R123H Secondary Mutations EXAMPLE: Trisomy 7 Mutually Exclusive BCL2, BCL6 rearrangement
Epigenomic Alterations
KMT2D, H3K4 methyltransferase, CREBBP Histone acetyltransferase (HAT) enzyme, and EZH2 SET domain histone methyltransferase mutations
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 |
editv4:Genes and Main Pathways InvolvedThe content below was from the old template. Please incorporate above.BCR-NFκB, JAK/STAT; mTORC signaling
Genetic Diagnostic Testing Methods
Surgical excision preferred; FISH or PCR for BCL2 rearrangement; preserve frozen tissue for further molecular testing
Familial Forms
SNPs within HLA class I or II genes [8] or homozygosity of HLA class II genes [9]
Additional Information
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
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)
- ↑ 1.0 1.1 Alaggio, Rita; et al. (2022). "The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms". Leukemia. 36 (7): 1720–1748. doi:10.1038/s41375-022-01620-2. ISSN 0887-6924. PMC 9214472 Check
|pmc=value (help). PMID 35732829 Check|pmid=value (help). - ↑ Carbone, Antonino; et al. (2012-03). "In situ follicular lymphoma: pathologic characteristics and diagnostic features: In situ follicular lymphoma". Hematological Oncology. 30 (1): 1–7. doi:10.1002/hon.993. Check date values in:
|date=(help) - ↑ Ferry, Judith A. (2010-12-01). "Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ". Surgical Pathology Clinics. Current Concepts in Hematopathology. 3 (4): 877–906. doi:10.1016/j.path.2010.08.002. ISSN 1875-9181.
- ↑ 4.0 4.1 Cite error: Invalid
<ref>tag; no text was provided for refs named:12
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: “Follicular lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Follicular_lymphoma.