# Angioimmunoblastic T-cell lymphoma
**Angioimmunoblastic T-cell lymphoma** (AITL) is an aggressive (fast-growing) type of T-cell non-[Hodgkin lymphoma](https://www.edgepedia.org/hodgkin-lymphoma) marked by enlarged lymph nodes and hypergammaglobulinemia, meaning increased antibodies in the blood; other symptoms may include a skin rash, fever, weight loss, or night sweats[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/angioimmunoblastic-t-cell-lymphoma). It is a rare mature T-cell malignancy characterized by an intense inflammatory reaction and immune dysregulation, and its normal cell of origin is the T-follicular helper (TFH) cell, an effector T lymphocyte that activates B cells within the germinal center[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/). In the fifth edition of the WHO Classification of Haematolymphoid Tumours the entity was renamed nodal T-follicular helper cell lymphoma, angioimmunoblastic type (nTFHL-AI), although most recent studies continue to use the term AITL[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC12198265/).
| Key fact | Detail |
|---|---|
| Disease type | Aggressive T-cell non-Hodgkin lymphoma; second most frequent subtype of mature T-cell lymphoma in the Western world[1](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/angioimmunoblastic-t-cell-lymphoma) • [2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/) |
| Frequency | About 1–2% of all non-Hodgkin lymphomas and 15–20% of peripheral T-cell lymphoma cases[4](https://www.nature.com/articles/s41409-026-03037-2) • [5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) |
| Cell of origin | T-follicular helper cells, confirmed by gene expression profiling in 2007[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/) • [6](https://haematologica.org/article/download/haematol.2023.282716/76292) |
| Recurrent mutations | TET2 in 70–80% of cases, RHOA in 50–70% (over 90% of these G17V), IDH2 in 20–30% (R172), DNMT3A in 10–25%[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) |
| Typical presentation | Advanced-stage disease, lymphadenopathy, B symptoms, immune dysregulation; up to 70% have bone marrow involvement[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) |
| Prognosis | 5-year overall survival about 30% despite intensive therapy; median survival does not exceed three years[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC5499521/) • [5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) |
| First-line therapy | Anthracycline-based chemotherapy, typically CHOP or CHOP-like regimens[4](https://www.nature.com/articles/s41409-026-03037-2) • [5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) |
## Clinical presentation
AITL affects mostly elderly adults, is more common in older men, and most patients are at a late stage when first diagnosed[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC5499521/) • [5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). The main manifestations are lymphadenopathy and [B symptoms](https://www.edgepedia.org/b-symptoms) (fever, night sweats, weight loss), which may be accompanied by hemolysis, anemia, hepatomegaly, and splenomegaly[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). Because the malignant TFH cells normally promote B-cell proliferation and antibody production, their dysfunction triggers autoimmune-type symptoms, and laboratory tests can show increased lactate dehydrogenase, reactive plasma cells, and polyclonal globulin[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). More than 50% of patients have skin symptoms, such as maculopapular rash and itching, and up to 70% have bone marrow involvement with polymorphic cell infiltration[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). This pattern of inflammatory and immune manifestations has been called the "immunodysplastic syndrome" typical of AITL[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/).
## Pathology and diagnosis
Diagnosis requires a biopsy of tumor tissue[8](https://lymphoma.org/wp-content/uploads/2024/10/Angioimmunoblastic_T_Cell_Lymphoma_Fact_Sheet_2024.pdf). Histologically, AITL partially or completely disrupts lymph node architecture, shows marked proliferation of blood vessels including high endothelial venules, and expands follicular dendritic cell networks, with a polymorphous infiltrate of neoplastic T cells and inflammatory cells[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). The tumor cells are small to medium with clear cytoplasm and cluster around blood vessels; large EBV-positive B immunoblasts, some resembling Reed-Sternberg cells of Hodgkin lymphoma, are typically present[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). The neoplastic cells express TFH markers such as CD4, PD-1, and CXCL13, which confirm their origin[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full).
The inflammatory background, in which tumor cells are only a minority of the tissue, is a main reason AITL is easily misdiagnosed, and early histological patterns can resemble reactive lymph node hyperplasia[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). The spectrum of clinical and histopathological features presents diagnostic challenges[9](https://www.sciencedirect.com/science/article/pii/S0046817724002053).
## Molecular pathogenesis
AITL follows a multistep, two-hit model. Early mutations in epigenetic regulatory genes, chiefly TET2 and DNMT3A, arise in hematopoietic stem and progenitor cells and promote clonal expansion, creating a pre-malignant field; secondary driver mutations, most notably RHOA and IDH2, then emerge within the TFH cell lineage and drive malignant transformation[3](https://pmc.ncbi.nlm.nih.gov/articles/PMC12198265/). TET2-inactivating mutations occur in 70–80% of cases and are considered early events; DNMT3A mutations are found in 10–25%, often alongside TET2 mutations[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full).
**RHOA G17V.** RHOA encodes a small GTPase involved in proliferation, survival, and cytoskeleton dynamics. Mutations are present in 50–70% of AITL cases, with over 90% being the G17V mutation, which activates the [T-cell receptor](https://www.edgepedia.org/t-cell-receptor) pathway by binding to VAV1; mouse models carrying this mutation develop AITL-like lesions[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). TET2 mutations co-occur with RHOA G17V in 60–70% of AITL patients[10](https://doi.org/10.1146/annurev-immunol-080223-044610).
**IDH2 R172.** IDH2 mutations, present in 20–30% of cases and specific to position R172, produce the oncometabolite 2-hydroxyglutarate, which impairs DNA and histone demethylation and promotes lymphoma development[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full) • [7](https://pmc.ncbi.nlm.nih.gov/articles/PMC5499521/).
**Downstream effects.** The transformed TFH cells secrete cytokines and chemokines including IL-6, IL-21, CXCL-13, and VEGF, which shape a defective tumor microenvironment characterized by expansion of follicular dendritic cells, vessels, and EBV-positive immunoblasts[2](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/). Recurrent changes in T-cell receptor pathway genes such as [PLCG1](https://www.edgepedia.org/plcg1), CD28, VAV1, and FYN occur in nearly half of cases[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full).
## Treatment
There is no standardized treatment for AITL. Standard first-line therapy typically consists of anthracycline-based chemotherapy, with or without etoposide depending on patient age, usually the [CHOP regimen](https://www.edgepedia.org/chop-regimen) (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a CHOP-like regimen[4](https://www.nature.com/articles/s41409-026-03037-2) • [5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). Its efficacy is poor, the remission period is short, and the recurrence rate is high[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full).
**Transplantation.** Patients who achieve complete remission and have favorable performance status are often candidates for autologous hematopoietic cell transplantation. In the international T-cell Project, patients who underwent consolidative autologous transplantation in first complete remission had 5-year overall survival of 89% versus 52% for transplant-eligible patients (age 65 or younger) who did not, and 5-year progression-free survival of 79% versus 31%[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC8493974/). Allogeneic transplantation has emerged as a potentially curative option for relapsed disease after autologous transplant, possibly owing to a graft-versus-lymphoma effect mediated by donor immune cells[4](https://www.nature.com/articles/s41409-026-03037-2).
**Epigenetic therapies.** The mutation profile has led to epigenetic modifying strategies. AITL and other TFH-type peripheral T-cell lymphomas may have higher response rates to histone deacetylase inhibitors such as romidepsin and belinostat compared with non-TFH lymphomas, and the hypomethylating agent azacitidine has shown high response rates as a single agent and combined with romidepsin. However, the randomized phase 3 Ro-[CHOP trial](https://www.edgepedia.org/chop-trial) failed to demonstrate a progression-free survival benefit for adding romidepsin to CHOP[12](https://ashpublications.org/blood/article-pdf/138/3/213/1814765/bloodbld2020010387.pdf).
## Prognosis
Despite intensive therapy, 5-year overall survival in AITL is about 30%, with little progress in the last two decades[7](https://pmc.ncbi.nlm.nih.gov/articles/PMC5499521/), and the median survival time does not exceed three years[5](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full). In the international T-cell Project cohort, 48% of deaths occurred within 1 year of diagnosis and 84% within 2 years; progressive disease accounted for 69% of deaths and infection for 16%[11](https://pmc.ncbi.nlm.nih.gov/articles/PMC8493974/). Recent research found that patients harboring triple mutations (TET2, IDH2 R172, and DNMT3A) have a significantly worse prognosis than those without them (p < 0.0001)[13](https://link.springer.com/article/10.1007/s00277-026-06753-3).
## Classification history
Immunophenotyping and gene expression profiling identified the TFH cell as the cell of origin of AITL in 2007, and this derivation became a cardinal defining feature of the disease[6](https://haematologica.org/article/download/haematol.2023.282716/76292). The fourth revised WHO edition grouped AITL with other nodal lymphomas of TFH origin under a single umbrella term, and the fifth edition introduced the family terminology of nodal T-follicular helper cell lymphomas (nTFHLs), with AITL now designated nTFHL, angioimmunoblastic type[14](https://doi.org/10.1136/jcp-2025-210074) • [15](https://www.mll.com/alaggio-et-al-the-5th-edition-of-the-world-health-organization-classification-of-haematolymphoid-tumours-lymphoid-neoplasms/alaggio-r_leukemia-2022_the-5th-edition-of-the-world-health-organization-classification-of-haematolymphoid-tumours.pdf). The International Consensus Classification instead considers one entity, follicular helper [T-cell lymphoma](https://www.edgepedia.org/t-cell-lymphoma), with angioimmunoblastic, follicular, and not-otherwise-specified subtypes[6](https://haematologica.org/article/download/haematol.2023.282716/76292).
## References
1. [Angioimmunoblastic T-cell lymphoma, NCI Dictionary of Cancer Terms](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/angioimmunoblastic-t-cell-lymphoma)
2. [Angioimmunoblastic T-cell lymphoma and correlated neoplasms with T-cell follicular helper phenotype, Frontiers in Oncology (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10169672/)
3. [Angioimmunoblastic T-cell lymphoma: a concise overview, Clinical and Experimental Medicine (2025)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12198265/)
4. [Reduced-intensity T-replete allogeneic stem cell transplantation in relapsed AITL, Bone Marrow Transplantation (2026)](https://www.nature.com/articles/s41409-026-03037-2)
5. [Advancing the understanding and management of AITL, Frontiers in Oncology (2025)](https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2025.1479179/full)
6. [Follicular helper T-cell lymphoma and the International Consensus Classification, Haematologica (2023)](https://haematologica.org/article/download/haematol.2023.282716/76292)
7. [The curious origins of Angioimmunoblastic T-Cell Lymphoma, PMC (2017)](https://pmc.ncbi.nlm.nih.gov/articles/PMC5499521/)
8. [Angioimmunoblastic T-Cell Lymphoma Fact Sheet, Lymphoma Research Foundation (2024)](https://lymphoma.org/wp-content/uploads/2024/10/Angioimmunoblastic_T_Cell_Lymphoma_Fact_Sheet_2024.pdf)
9. [Angioimmunoblastic T-cell lymphoma: Current Diagnostic Insights and Advances, Human Pathology (2025)](https://www.sciencedirect.com/science/article/pii/S0046817724002053)
10. [TET Enzymes in the Immune System, Annual Review of Immunology (2023)](https://doi.org/10.1146/annurev-immunol-080223-044610)
11. [Outcomes and prognostic factors in AITL: final report from the international T-cell Project, Blood (2021)](https://pmc.ncbi.nlm.nih.gov/articles/PMC8493974/)
12. [Outcomes and prognostic factors in AITL, Blood (PDF)](https://ashpublications.org/blood/article-pdf/138/3/213/1814765/bloodbld2020010387.pdf)
13. [Unraveling the many faces of AITL, Annals of Hematology (2026)](https://link.springer.com/article/10.1007/s00277-026-06753-3)
14. [The fifth edition of the WHO classification of mature T cell, NK cell and stroma-derived neoplasms, Journal of Clinical Pathology](https://doi.org/10.1136/jcp-2025-210074)
15. [The 5th edition of the WHO Classification of Haematolymphoid Tumours: Lymphoid Neoplasms, Leukemia (2022)](https://www.mll.com/alaggio-et-al-the-5th-edition-of-the-world-health-organization-classification-of-haematolymphoid-tumours-lymphoid-neoplasms/alaggio-r_leukemia-2022_the-5th-edition-of-the-world-health-organization-classification-of-haematolymphoid-tumours.pdf)
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*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Cardiovascular and blood conditions › Blood disorders (hematologic conditions) › Lymphomas › T-cell, NK-cell, and cutaneous lymphomas › Nodal T-cell lymphomas with T-follicular-helper phenotype*
*Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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License: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license