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)*
- Hayk Simonyan, MD
- Ian King, PhD, 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 |
Related Terminology
| Acceptable | Angioimmunoblastic T-cell lymphoma; follicular helper T-cell lymphoma, angioimmunoblastic type |
| Not Recommended | Peripheral T-cell lymphoma; angioimmunoblastic lymphadenopathy with dysproteinaemia; immunoblastic lymphadenopathy; lymphogranulomatosis X |
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 |
|---|---|---|---|---|---|---|---|
| CD28 | CTLA4::CD28, ICOS::CD28 | Increase costimulatory signaling | chr2q33 | Rare | D, P | No | Cooperates with RHOA/TET2 (PMID: 27369867, 26405154, 26819049) |
| ITK | ITK::SYK | Aberrant kinase signaling | t(5;9) | Rare | D | No | Non-defining lesion (PMID: 16341044) |
| TCL1A | TRB::TCL1A; TRA/TRD::TCL1A | TCR-driven overexpression | t(7;14), inv(14) | Rare | D | No | Historical finding (PMID: 2284141, 2293883) |
Note: No defining fusion; disease driven by mutations (PMID: 31092896)
_Comment: We probably don't need the short table below
| 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)
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 |
|---|---|---|---|---|---|---|
| 3,5,21 | Trisomy | Whole chr | — | D | No | Secondary (PMID: 7919378) |
| X | Gain | Whole chr | — | D | No | Secondary (PMID: 7919378) |
| 6q | Loss | 6q | — | D,P | No | Non-specific (PMID: 7919378) |
| 22q | Gain | 22q | — | D | No | CGH finding (PMID: 17044049) |
| 19 | Gain | Whole chr | — | D | No | Secondary (PMID: 17044049) |
| 11q13 | Gain | 11q13 | — | D | No | Uncertain relevance (PMID: 17044049) |
| 13q | Loss | 13q | — | D | No | Non-specific (PMID: 17044049) |
editv4:Genomic Gain/Loss/LOHThe content below was from the old template. Please incorporate above.
_Comment: We probably don't need the short table below
| Chromosome Number | Gain/Loss/Amp/LOH | Reference |
|---|---|---|
| 3,5,21 | Trisomy | [7] |
| X | Gain | [7] |
| 6q | Loss | [7] |
| 22q | Gain | [8] |
| 19 | Gain | [8] |
| 11q13 | Gain | [8] |
| 13q | Loss | [8] |
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 |
|---|---|---|---|---|---|
| TR rearrangement | T-cell clonality | 75–90% | D | No | May be negative if low tumor (PMID: 17448026, 33567811) |
| IG rearrangement | EBV+ B-cell clones | 25–30% | D | No | Reflects B-cell proliferation (PMID: 16931587) |
| Clonal hematopoiesis | TET2/DNMT3A early mutations | Common | D,P | No | Shared across lineages (PMID: 25510268, 34230608) |
| Hypermethylation (IDH2) | 2-HG mediated epigenetic change | Subset | D,P | No | Clear-cell subset (PMID: 26268241, 30952970) |
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[9] [10][11]
- Clonal rearrangement in immunoglobulin genes in 25-30% of AITL cases[9][11]
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 |
|---|---|---|---|---|---|---|
| TET2 | LOF mutations | Epigenetic regulator | 50–80% | D | No | Early event (PMID: 22760778) |
| DNMT3A | LOF mutations | Epigenetic regulator | 20–30% | D,P | No | Clonal hematopoiesis (PMID: 24345752) |
| RHOA | G17V hotspot | Signaling | ~70% | D | No | Key diagnostic mutation (PMID: 24413737, 24584070) |
| IDH2 | R172 mutations | Oncogene | 20–30% | D,P | No | AITL-specific subset (PMID: 22215888, 26268241) |
| VAV1 | Activating mutations | Oncogene | <10% | D | No | TCR signaling (PMID: 27369867) |
| PLCG1 | Activating mutations | Oncogene | <10% | D | No | TCR signaling (PMID: 27369867) |
| FYN | Activating mutations | Oncogene | <10% | D | No | TCR signaling (PMID: 24413734) |
| CD28 | GOF mutations | Oncogene | <10% | D,P | No | Poor prognosis (PMID: 26719098) |
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.
_Comment: We probably don't need the short table below
| 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%[12][2][13][14] |
| TET2 | Widely distributed | Tumor Suppressor | LOF | 50-80%[15][13] |
| DNMT3A | W305* | Tumor Suppressor | LOF | 20-30%[2][13] |
| RHOA | G17V; G17E; C16R; T19I; D120Y | Tumor Suppressor ONCOGENE | LOF GOF | 60-70%[16][17][18] |
| FYN | L174R; R176C; Y531H | Oncogene | GOF | up to 5-10%[19][18] |
| PLCG1 | S345F; G869E | Oncogene | GOF | up to 5-10%[19][2] |
| CD28 | D124V; D124E; T195P | Oncogene | GOF | up to 5-10%[19][20] |
| 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
| Gene | Alteration | Pathway | Outcome |
| TET2 | LOF | DNA demethylation | Dysregulated transcription (PMID: 25510268) |
| DNMT3A | LOF | DNA methylation | Abnormal differentiation (PMID: 25510268) |
| IDH2 | R172 | Oncometabolite | Hypermethylation (PMID: 27956631, 26268241) |
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 |
|---|---|---|
| TET2, DNMT3A, IDH2 | Epigenetic regulation | Aberrant gene expression (PMID: 25510268, 34230608) |
| RHOA, VAV1, PLCG1, FYN | TCR signaling | ↑ proliferation/survival (PMID: 28832024, 28062691) |
| CD28 alterations | Costimulation | Enhanced activation (PMID: 26405154, 26719098) |
| TFH program (PD1, ICOS, CXCL13) | TFH differentiation | B-cell interaction, immune dysregulation (PMID: 31117010) |
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][18][19][20] | Increased proliferation and survival |
| IDH2, TET2, and DNMT3A mutations | Histone modification and chromatin remodeling[2][13][14][15] | Abnormal gene expression program |
End of V4 Section
Genetic Diagnostic Testing Methods
- ≥2 TFH markers (PD1, ICOS, CD10, CXCL13) (PMID: 31283630)
- FDC expansion (CD21/CD23/CD35) (PMID: 24128129)
- RHOA G17V or IDH2 R172 supports diagnosis (PMID: 33567811)
- TR clonality testing supportive (PMID: 32476550)
- EBER ISH detects EBV+ B cells (PMID: 26045291)
- Flow cytometry: CD4+/PD1bright or CD10+ T cells (PMID: 27105079)
Familial Forms
None established. Sporadic disease associated with clonal hematopoiesis (PMID: 34230608).
Additional Information
Clinical:
Advanced stage, B symptoms, hepatosplenomegaly, immune dysregulation (PMID: 18292286)
Histology:
Polymorphous infiltrate, HEV proliferation, FDC expansion; patterns 1–3 (PMID: 11781247, 24128129)
Immunophenotype:
CD4+, TFH markers (PD1, ICOS, CD10, CXCL13) (PMID: 31283630)
Differential Diagnosis:
Reactive hyperplasia, PTCL-NOS, Hodgkin lymphoma mimics (PMID: 17448026)
Prognosis:
Poor; ~50% 3-year OS; worse with TET2/DNMT3A/IDH2 (PMID: 34292324, 33496747)
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; U, Vinatzer; M, Willheim; M, Raderer; A, Chott (2006). "Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma". PMID 16341044.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 M, Wang; S, Zhang; Ss, Chuang; M, Ashton-Key; E, Ochoa; N, Bolli; G, Vassiliou; Z, Gao; Mq, Du (2017). "Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling". doi:10.18632/oncotarget.14846. PMC 5392284. PMID 28148900.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ Mf, Cosimi; I, Casagranda; G, Ghiazza; G, Rossi; P, Galvani (1990). "Rearrangements on chromosomes 7 and 14 with breakpoints at 7q35 and 14q11 in angioimmunoblastic lymphadenopathy and IBL-like T-cell lymphoma". PMID 2284141.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ B, Schlegelberger; A, Feller; A, Himmler; W, Grote (1990). "Inv(14)(q11q32) in one of four different clones in a case of angioimmunoblastic lymphadenopathy". PMID 2293883.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ E, Leich; E, Haralambieva; A, Zettl; A, Chott; T, Rüdiger; S, Höller; Hk, Müller-Hermelink; G, Ott; A, Rosenwald (2007). "Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas". PMID 17582237.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ Hy, Yoo; P, Kim; Ws, Kim; Sh, Lee; S, Kim; Sy, Kang; Hy, Jang; Je, Lee; J, Kim (2016). "Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma". doi:10.3324/haematol.2015.139253. PMC 5013939. PMID 26819049.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 7.0 7.1 7.2 B, Schlegelberger; Y, Zhang; K, Weber-Matthiesen; W, Grote (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.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ 8.0 8.1 8.2 8.3 C, Thorns; B, Bastian; D, Pinkel; R, Roydasgupta; J, Fridlyand; H, Merz; M, Krokowski; Hw, Bernd; Ac, Feller (2007). "Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach". PMID 17044049.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ 9.0 9.1 Ad, Attygalle; Ss, Chuang; Tc, Diss; Mq, Du; Pg, Isaacson; A, Dogan (2007). "Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics". PMID 17448026.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ L, de Leval; C, Gisselbrecht; P, Gaulard (2010). "Advances in the understanding and management of angioimmunoblastic T-cell lymphoma". PMID 19961485.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ 11.0 11.1 Bt, Tan; Ra, Warnke; Da, Arber (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.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ Ra, Cairns; J, Iqbal; F, Lemonnier; C, Kucuk; L, de Leval; Jp, Jais; M, Parrens; A, Martin; L, Xerri (2012). "IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2011-11-391748. PMC 3293643. PMID 22215888.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 13.0 13.1 13.2 13.3 O, Odejide; O, Weigert; Aa, Lane; D, Toscano; Ma, Lunning; N, Kopp; S, Kim; D, van Bodegom; S, Bolla (2014). "A targeted mutational landscape of angioimmunoblastic T-cell lymphoma". doi:10.1182/blood-2013-10-531509. PMC 4260974. PMID 24345752.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 14.0 14.1 C, Wang; Tw, McKeithan; Q, Gong; W, Zhang; A, Bouska; A, Rosenwald; Rd, Gascoyne; X, Wu; J, Wang (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.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 15.0 15.1 F, Lemonnier; L, Couronné; M, Parrens; Jp, Jaïs; M, Travert; L, Lamant; O, Tournillac; T, Rousset; B, Fabiani (2012). "Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters". PMID 22760778.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ M, Sakata-Yanagimoto; T, Enami; K, Yoshida; Y, Shiraishi; R, Ishii; Y, Miyake; H, Muto; N, Tsuyama; A, Sato-Otsubo (2014). "Somatic RHOA mutation in angioimmunoblastic T cell lymphoma". PMID 24413737.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ Hy, Yoo; Mk, Sung; Sh, Lee; S, Kim; H, Lee; S, Park; Sc, Kim; B, Lee; K, Rho (2014). "A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma". PMID 24584070.
{{cite journal}}: Cite journal requires|journal=(help) - ↑ 18.0 18.1 18.2 T, Palomero; L, Couronné; H, Khiabanian; My, Kim; A, Ambesi-Impiombato; A, Perez-Garcia; Z, Carpenter; F, Abate; M, Allegretta (2014). "Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas". doi:10.1038/ng.2873. PMC 3963408. PMID 24413734.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 19.0 19.1 19.2 19.3 Sh, Lee; Js, Kim; J, Kim; Sj, Kim; Ws, Kim; S, Lee; Yh, Ko; Hy, Yoo (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.
{{cite journal}}: Cite journal requires|journal=(help)CS1 maint: PMC format (link) - ↑ 20.0 20.1 J, Rohr; S, Guo; J, Huo; A, Bouska; C, Lachel; Y, Li; Pd, Simone; W, Zhang; Q, Gong (2016). "Recurrent activating mutations of CD28 in peripheral T-cell lymphomas". doi:10.1038/leu.2015.357. PMC 5688878. PMID 26719098.
{{cite journal}}: Cite journal requires|journal=(help)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 04/21/2026, https://ccga.io/index.php/HAEM5:Nodal_TFH_cell_lymphoma,_angioimmunoblastic-type.