Nodal TFH cell lymphoma, angioimmunoblastic-type
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:Angioimmunoblastic T-cell Lymphoma.
(General Instructions – The focus of these pages is the clinically significant genetic alterations in each disease type. This is based on up-to-date knowledge from multiple resources such as PubMed and the WHO classification books. The CCGA is meant to be a supplemental resource to the WHO classification books; the CCGA captures in a continually updated wiki-stye manner the current genetics/genomics knowledge of each disease, which evolves more rapidly than books can be revised and published. If the same disease is described in multiple WHO classification books, the genetics-related information for that disease will be consolidated into a single main page that has this template (other pages would only contain a link to this main page). Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column in a table, click nearby within the table and select the > symbol that appears. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support.)
Primary Author(s)*
- Sara Akhavanfard, M.D., Ph.D.
- Ruthann Pfau, Ph.D., FACMG
WHO Classification of Disease
Structure | Disease |
---|---|
Book | Haematolymphoid Tumours (5th ed.) |
Category | T-cell and NK-cell lymphoid proliferations and lymphomas |
Family | Mature T-cell and NK-cell neoplasms |
Type | Nodal T-follicular helper (TFH) cell lymphoma |
Subtype(s) | Nodal TFH cell lymphoma, angioimmunoblastic-type |
WHO Essential and Desirable Genetic Diagnostic Criteria
(Instructions: The table will have the diagnostic criteria from the WHO book autocompleted; remove any non-genetics related criteria. If applicable, add text about other classification systems that define this entity and specify how the genetics-related criteria differ.)
WHO Essential Criteria (Genetics)* | |
WHO Desirable Criteria (Genetics)* | |
Other Classification |
*Note: These are only the genetic/genomic criteria. Additional diagnostic criteria can be found in the WHO Classification of Tumours.
Related Terminology
(Instructions: The table will have the related terminology from the WHO autocompleted.)
Acceptable | |
Not Recommended |
Gene Rearrangements
Put your text here and fill in the table (Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
---|---|---|---|---|---|---|---|
EXAMPLE: ABL1 | EXAMPLE: BCR::ABL1 | EXAMPLE: The pathogenic derivative is the der(22) resulting in fusion of 5’ BCR and 3’ABL1. | EXAMPLE: t(9;22)(q34;q11.2) | EXAMPLE: Common (CML) | EXAMPLE: D, P, T | EXAMPLE: Yes (WHO, NCCN) | EXAMPLE:
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference). BCR::ABL1 is generally favorable in CML (add reference). |
EXAMPLE: CIC | EXAMPLE: CIC::DUX4 | EXAMPLE: Typically, the last exon of CIC is fused to DUX4. The fusion breakpoint in CIC is usually intra-exonic and removes an inhibitory sequence, upregulating PEA3 genes downstream of CIC including ETV1, ETV4, and ETV5. | EXAMPLE: t(4;19)(q25;q13) | EXAMPLE: Common (CIC-rearranged sarcoma) | EXAMPLE: D | EXAMPLE:
DUX4 has many homologous genes; an alternate translocation in a minority of cases is t(10;19), but this is usually indistinguishable from t(4;19) by short-read sequencing (add references). | |
EXAMPLE: ALK | EXAMPLE: ELM4::ALK
|
EXAMPLE: Fusions result in constitutive activation of the ALK tyrosine kinase. The most common ALK fusion is EML4::ALK, with breakpoints in intron 19 of ALK. At the transcript level, a variable (5’) partner gene is fused to 3’ ALK at exon 20. Rarely, ALK fusions contain exon 19 due to breakpoints in intron 18. | EXAMPLE: N/A | EXAMPLE: Rare (Lung adenocarcinoma) | EXAMPLE: T | EXAMPLE:
Both balanced and unbalanced forms are observed by FISH (add references). | |
EXAMPLE: ABL1 | EXAMPLE: N/A | EXAMPLE: Intragenic deletion of exons 2–7 in EGFR removes the ligand-binding domain, resulting in a constitutively active tyrosine kinase with downstream activation of multiple oncogenic pathways. | EXAMPLE: N/A | EXAMPLE: Recurrent (IDH-wildtype Glioblastoma) | EXAMPLE: D, P, T | ||
editv4:Chromosomal Rearrangements (Gene Fusions)The content below was from the old template. Please incorporate above.
Chromosomal Rearrangement | Genes in Fusion (5’ or 3’ Segments) | Pathogenic Derivative | Reference |
---|---|---|---|
t(5;9)(q33;q22) | ITK/SYK | der(5); der(9) | [1][2] |
t(7;14)(q35;q32.1) | TRB/TCL1A | der(7); der(14) | [3] |
t(14;14)(q11;q32.1) / inv(14)(q11q32.1) | TRA-TRD/TCL1A | der(14) | [4][5] |
chr(2)(q33.2) | CTLA4/CD28 | der(2) | [6] |
End of V4 Section
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)
- Overall prognosis is poor[7][8]
- Median survival < 3 years, even with aggressive treatment[7][8]
- Male sex, mediastinal lymphadenopathy, and anemia adversely affect the survival[7]
Suggested Treatment Regimens based on NCCN Guideline Version 1.2020 (TCEL-B 3 of 5)
Second-line therapy (with intention to transplant) and subsequent therapy:
- Clinical Trial preferred
- Preferred regimens
- Single Agents (alphabetical order)
- Belinostat
- Brentuximab Vedotin for CD30+ AITL
- Romidepsin
- Combination Regimens
- DHAP(Dexamethasone, Cisplatin, Cytarabine)
- ESHAP (Etoposide, Methylprednisolone, Citarabine, Cisplatin)
- GDP (Gemcitabine, Dexamethasone, Cisplatin)
- GemOx (Gemcitabine, Oxaliplatin)
- ICE (Ifosfamide, Carboplatin, Etoposide)
- Single Agents (alphabetical order)
- Other recommended regimens
- Single Agents (alphabetical order)
- Bendamustine
- Gemcitabine
- Lenalidomide
- Pralatrexate
- Single Agents (alphabetical order)
Second-line or initial palliative intent therapy (no intention to transplant) and subsequent therapy:
- Clinical Trial preferred
- Preferred regimens
- Single Agents (alphabetical order)
- Belinostat
- Brentuximab Vedotin for CD30+ AITL
- Romidepsin
- Single Agents (alphabetical order)
- Other recommended regimen (alphabetical order)
- Alemtuzumab
- Bendamustine
- Bertezomib (categort 2B)
- Cyclophosphamide and/or Etoposide (IV or PO)
- Cyclosporine
- Gemcitabine
- Lenalidomide
- Pralatrexate
- Radiation therapy
End of V4 Section
Individual Region Genomic Gain/Loss/LOH
Put your text here and fill in the table (Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.)
Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
---|---|---|---|---|---|---|
EXAMPLE:
7 |
EXAMPLE: Loss | EXAMPLE:
chr7 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE: 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 references). |
EXAMPLE:
8 |
EXAMPLE: Gain | EXAMPLE:
chr8 |
EXAMPLE:
Unknown |
EXAMPLE: D, P | EXAMPLE:
Common recurrent secondary finding for t(8;21) (add references). | |
EXAMPLE:
17 |
EXAMPLE: Amp | EXAMPLE:
17q12; chr17:39,700,064-39,728,658 [hg38; 28.6 kb] |
EXAMPLE:
ERBB2 |
EXAMPLE: D, P, T | EXAMPLE:
Amplification of ERBB2 is associated with HER2 overexpression in HER2 positive breast cancer (add references). Add criteria for how amplification is defined. | |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.
Chromosome Number | Gain/Loss/Amp/LOH | Reference |
---|---|---|
3,5,21 | Trisomy | [9] |
X | Gain | [9] |
6q | Loss | [9] |
22q | Gain | [10] |
19 | Gain | [10] |
11q13 | Gain | [10] |
13q | Loss | [10] |
End of V4 Section
Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: Included in this category are alterations such as 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; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
---|---|---|---|---|---|
EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | EXAMPLE: Common (Oligodendroglioma) | EXAMPLE: D, P | ||
EXAMPLE:
Microsatellite instability - hypermutated |
EXAMPLE: Common (Endometrial carcinoma) | EXAMPLE: P, T | |||
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
- Clonal rearrangement in T-Cell receptor gene in 75-90% of AITL cases[11] [12][13]
- Clonal rearrangement in immunoglobulin genes in 25-30% of AITL cases[11][13]
End of V4 Section
Gene Mutations (SNV/INDEL)
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
---|---|---|---|---|---|---|
EXAMPLE:EGFR
|
EXAMPLE: Exon 18-21 activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (lung cancer) | EXAMPLE: T | EXAMPLE: Yes (NCCN) | EXAMPLE: Exons 18, 19, and 21 mutations are targetable for therapy. Exon 20 T790M variants cause resistance to first generation TKI therapy and are targetable by second and third generation TKIs (add references). |
EXAMPLE: TP53; Variable LOF mutations
|
EXAMPLE: Variable LOF mutations | EXAMPLE: Tumor Supressor Gene | EXAMPLE: Common (breast cancer) | EXAMPLE: P | EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |
EXAMPLE: BRAF; Activating mutations | EXAMPLE: Activating mutations | EXAMPLE: Oncogene | EXAMPLE: Common (melanoma) | EXAMPLE: T | ||
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, 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.
Gene | Mutation‡ | Oncogene/Tumor Suppressor/Other | Presumed Mechanism
(LOF/GOF/Other; Driver/Passenger) |
Prevalence
(COSMIC/TCGA/Other) |
---|---|---|---|---|
IDH2 | R172S; R172G;R172K | Tumor Suppressor ONCOGENE | LOF GOF | 20-30%[14][2][15][16] |
TET2 | Widely distributed | Tumor Suppressor | LOF | 50-80%[17][15] |
DNMT3A | W305* | Tumor Suppressor | LOF | 20-30%[2][15] |
RHOA | G17V; G17E; C16R; T19I; D120Y | Tumor Suppressor ONCOGENE | LOF GOF | 60-70%[18][19][20] |
FYN | L174R; R176C; Y531H | Oncogene | GOF | up to 5-10%[21][20] |
PLCG1 | S345F; G869E | Oncogene | GOF | up to 5-10%[21][2] |
CD28 | D124V; D124E; T195P | Oncogene | GOF | up to 5-10%[21][22] |
TNFRSF21 | S428fs*S1 | Tumor Suppressor | LOF | [2] |
CCND3 | Q280* | Tumor Suppressor | LOF | [2] |
SAMSN1 | R153* | Tumor Suppressor | LOF | [2] |
‡More comprehensive account of specific mutations in these genes can be found in cBioPortal and COSMIC.
End of V4 Section
Epigenomic Alterations
- Frequent mutation in epigenetic modifiers like: [2][15][16][17]
- IDH2 (20-30%)
- TET2 (50-80%)
- DNMT3A (20-30%)
Genes and Main Pathways Involved
Put your text here and fill in the table (Instructions: Please include references throughout the table. Do not delete the table.)
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.
Molecular Features | Pathway | Pathophysiologic Outcome |
---|---|---|
FYN, PLCG1, and CD28 mutations | T-cell receptor signaling pathway[2][20][21][22] | Increased proliferation and survival |
IDH2, TET2, and DNMT3A mutations | Histone modification and chromatin remodeling[2][15][16][17] | Abnormal gene expression program |
End of V4 Section
Genetic Diagnostic Testing Methods
- Clinical, morphological, and immunophenotypic findings are generally sufficient for diagnosis
- IDH2 R172 mutations are specific to AITL
- T-Cell receptor and immunoglobulin genes rearrangement detection by karyotyping and FISH analysis
Familial Forms
Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)
Additional Information
N/A
Links
References
(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. 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. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted.)
- ↑ B, Streubel; et al. (2006). "Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma". PMID 16341044.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 M, Wang; et al. (2017). "Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling". doi:10.18632/oncotarget.14846. PMC 5392284. PMID 28148900.CS1 maint: PMC format (link)
- ↑ Mf, Cosimi; et al. (1990). "Rearrangements on chromosomes 7 and 14 with breakpoints at 7q35 and 14q11 in angioimmunoblastic lymphadenopathy and IBL-like T-cell lymphoma". PMID 2284141.
- ↑ B, Schlegelberger; et al. (1990). "Inv(14)(q11q32) in one of four different clones in a case of angioimmunoblastic lymphadenopathy". PMID 2293883.
- ↑ E, Leich; et al. (2007). "Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas". PMID 17582237.
- ↑ Hy, Yoo; et al. (2016). "Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma". doi:10.3324/haematol.2015.139253. PMC 5013939. PMID 26819049.CS1 maint: PMC format (link)
- ↑ 7.0 7.1 7.2 N, Mourad; et al. (2008). "Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials". doi:10.1182/blood-2007-08-105759. PMC 2343588. PMID 18292286.CS1 maint: PMC format (link)
- ↑ 8.0 8.1 J, Vose; et al. (2008). "International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes". PMID 18626005.
- ↑ 9.0 9.1 9.2 B, Schlegelberger; et al. (1994). "Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics". PMID 7919378.
- ↑ 10.0 10.1 10.2 10.3 C, Thorns; et al. (2007). "Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach". PMID 17044049.
- ↑ 11.0 11.1 Ad, Attygalle; et al. (2007). "Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics". PMID 17448026.
- ↑ L, de Leval; et al. (2010). "Advances in the understanding and management of angioimmunoblastic T-cell lymphoma". PMID 19961485.
- ↑ 13.0 13.1 Bt, Tan; et al. (2006). "The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations". doi:10.2353/jmoldx.2006.060016. PMC 1867616. PMID 16931587.CS1 maint: PMC format (link)
- ↑ Ra, Cairns; et al. (2012). "IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2011-11-391748. PMC 3293643. PMID 22215888.CS1 maint: PMC format (link)
- ↑ 15.0 15.1 15.2 15.3 15.4 O, Odejide; et al. (2014). "A targeted mutational landscape of angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2013-10-531509. PMC 4260974. PMID 24345752.CS1 maint: PMC format (link)
- ↑ 16.0 16.1 16.2 C, Wang; et al. (2015). "IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2015-05-644591. PMC 4600014. PMID 26268241.CS1 maint: PMC format (link)
- ↑ 17.0 17.1 17.2 F, Lemonnier; et al. (2012). "Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters". PMID 22760778.
- ↑ M, Sakata-Yanagimoto; et al. (2014). "Somatic RHOA mutation in angioimmunoblastic T cell lymphoma". PMID 24413737.
- ↑ Hy, Yoo; et al. (2014). "A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma". PMID 24584070.
- ↑ 20.0 20.1 20.2 T, Palomero; et al. (2014). "Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas". doi:10.1038/ng.2873. PMC 3963408. PMID 24413734.CS1 maint: PMC format (link)
- ↑ 21.0 21.1 21.2 21.3 Sh, Lee; et al. (2015). "A highly recurrent novel missense mutation in CD28 among angioimmunoblastic T-cell lymphoma patients". doi:10.3324/haematol.2015.133074. PMC 4666342. PMID 26405154.CS1 maint: PMC format (link)
- ↑ 22.0 22.1 J, Rohr; et al. (2016). "Recurrent activating mutations of CD28 in peripheral T-cell lymphomas". doi:10.1038/leu.2015.357. PMC 5688878. PMID 26719098.CS1 maint: PMC format (link)
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 Associate Editor or other CCGA representative. When pages have a major update, the new author will be acknowledged at the beginning of the page, and those who contributed previously will be acknowledged below as a prior author.
Prior Author(s):
*Citation of this Page: “Nodal TFH cell lymphoma, angioimmunoblastic-type”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/11/2025, https://ccga.io/index.php/HAEM5:Nodal_TFH_cell_lymphoma,_angioimmunoblastic-type.