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angioimmunoblastic T-cell lymphoma

Monday 1 March 2004

angioimmunoblastic lymphadenopathy


Definition: Angioimmunoblastic T-cell lymphoma (AITL) is a systemic disease that often has evidence of extranodal involvement at presentation. Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon, but aggressive nodal peripheral T-cell lymphoma. AITL represents a clonal T-cell proliferation with a stable T-cell clone throughout the disease.


- JRC:7299 : Angioimmunoblastic lymphadenopathy.


Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT) (also known as "Angioimmunoblastic lymphadenopathy with dysproteinemia") is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lymph node infiltrate showing a marked increase in follicular dendritic cells (FDCs) and high endothelial venules (HEVs) and systemic involvement.

It is also known as immunoblastic lymphadenopathy (Lukes-Collins Classification) and AILD-type (lymphogranulomatosis X) T-cell lymphoma (Kiel Classification)

The typical patient with angioimmunoblastic T-cell lymphoma (AILT) is either middle-aged or elderly, and no gender preference for this disease has been observed.

AILT comprises 15-20% of peripheral T-cell lymphomas and 1-2% of all non-Hodgkin lymphomas.

Partial nodal involvement with hyperplastic follicles is seen in early AITL and at relapse. (17592275)

When "morphologic high-grade transformation" occurs, it is usually due to a secondary (often EBV-associated) B-cell lymphoma, rather than a T-cell neoplasm. (17592275)

Clinical synopsis

Patients with this disease usually present at an advanced stage and show systemic involvement. The clinical findings typically include a pruritic skin rash and possibly edema, ascites, pleural effusions, and arthritis.

The classical laboratory finding is polyclonal hypergammaglobulinemia, and other immunoglobulin derangements are also seen, including hemolytic anemia with cold agglutinins, circulating immune complexes, anti-smooth muscle antibodies, and positive rheumatoid factor.

Due to the systemic nature of this disease, neoplastic cells can be found in lymph nodes, liver, spleen, skin, and bone marrow.


- complex infiltration pattern

  • The growth of angioimmunoblastic T-cell lymphoma (AIL) in lymph node often produces complex patterns of neoplastic T cells and non-neoplastic B cells.

- partially effacement of nodal architecture

  • The normal architecture of a lymph node is partially effaced by a polymorphous infiltrate and residual follicles are commonly seen.

- nodal polymorphous cellular infiltrate

  • The polymorphous infiltrate consists of lymphocytes of moderate size with pale/clear cytoplasm and smaller reactive lymphocytes, eosinophils, histiocytes, plasma cells, and follicular dendritic cells.
  • In addition, blast-like B-cells are occasionally seen.

- aborization of high endothelial venules and proliferation of high endothelial venules

  • A classic morphological finding is the aborization and proliferation of high endothelial venules.

- possible hyperplastic germinal centers
- possible Reed-Sternberg cells


- AILT typically has the phenotype of a mixture of CD4+ and CD8+ T-cells, with a CD4:CD8 ratio greater than unity.
- Polyclonal plasma cells and CD21+ follicular dendritic cells are also seen.
- CD10+ (aberrant expression of CD10) (14707864)
- c-maf overexpression (MAF MIM.177075) (18059226)
- PD-1 expression (20087161, 16819321)
- CXCL13 expression (16625095)

Molecular biology

Clonal T-cell receptor gene rearrangements are detected in 75% of cases, and immunoglobin gene rearrangements are seen in 10% of cases, and these cases are believed to be due to expanded EBV-driven B-cell populations.

Similarly, EBV-related sequences can be detected most cases, usually in B-cells but occasionally in T-cells.


Trisomy 3, trisomy 5, and +X are the most frequent chromosomal abnormalities found in cases.


This disease was originally thought to be a premalignant condition, termed "angioimmunoblastic lymphadenopathy", and this atypical reactive lymphadenopathy carried a risk for transformation into a lymphoma.

Currently, it is postulated that the originating cell for this disease is a mature (post-thymic) CD4+ T-cell that arises de novo, although some researchers argue that there is a premalignant subtype of this disease.

The Epstein–Barr virus (EBV) is observed in the majority of cases, and the virus has been found in the reactive B-cells that comprise part of the polymorphous infiltrate of this disease and in the neoplastic T-cells.

Immunodeficiency is also seen with this disease, but it is a sequela to the condition and not a predisposing factor.

Expression profile

- The molecular profile of AITLs is characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T(FH)) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). (17284527)

CGH (17044049)

- gains

  • 11p11-q14 gains (11q13 gains)
  • Chr.19 gains
  • 22q gains

- losses

  • 13q losses

See also

- Lymphomas: T-cell lymphomas
- nodal follicular compartment
- nodal paracortical compartment (nodal paracortex)
- nodal sinusoidal compartment
- germinal centers
- D2-40+ CD31+ perifollicular sinus around most of the follicular compartment
- bcl-6-negative monocytoid B-cells
- Epstein-Barr virus (EBV)
- histiocyte-rich B-cell proliferations
- prominence of the perifollicular sinus
- reactive lymphadenitis
- lymphatic
- cytokines
- lymph fluid
- normal and altered germinal center reactions
- sinus drainage
- nodal T-cell lymphomas


- Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Attygalle AD, Kyriakou C, Dupuis J, Grogg KL, Diss TC, Wotherspoon AC, Chuang SS, Cabeçadas J, Isaacson PG, Du MQ, Gaulard P, Dogan A. Am J Surg Pathol. 2007 Jul;31(7):1077-88. PMID: 17592275

- Regulatory T-cell depletion in angioimmunoblastic T-cell lymphoma. Bruneau J, Canioni D, Renand A, Marafioti T, Paterson JC, Martin-Garcia N, Gaulard P, Delfau MH, Hermine O, Macintyre E, Brousse N, Asnafi V. Am J Pathol. 2010 Aug;177(2):570-4.PMID: 20566750

- Mourad N, Mounier N, Briere J, Raffoux E, Delmer A, Feller A, Meijer CJ, Emile JF, Bouabdallah R, Bosly A, Diebold J, Haioun C, Coiffier B, Gisselbrecht C, Gaulard P. Clinical, biological and pathological features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d’Etude des Lymphomes de l’Adulte (GELA) trials. Blood. 2008 Feb 21; PMID: 18292286

- Histologic evolution of angioimmunoblastic T-cell lymphoma in consecutive biopsies: clinical correlation and insights into natural history and disease progression. Attygalle AD, Kyriakou C, Dupuis J, Grogg KL, Diss TC, Wotherspoon AC, Chuang SS, Cabeçadas J, Isaacson PG, Du MQ, Gaulard P, Dogan A. Am J Surg Pathol. 2007 Jul;31(7):1077-88. PMID: 17592275

- Murakami YI, Yatabe Y, Sakaguchi T, Sasaki E, Yamashita Y, Morito N, Yoh K, Fujioka Y, Matsuno F, Hata H, Mitsuya H, Imagawa S, Suzuki A, Esumi H, Sakai M, Takahashi S, Mori N. c-Maf expression in angioimmunoblastic T-cell lymphoma. Am J Surg Pathol. 2007 Nov;31(11):1695-702. PMID: 18059226

- Thorns C, Bastian B, Pinkel D, Roydasgupta R, Fridlyand J, Merz H, Krokowski M, Bernd HW, Feller AC. Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach. Genes Chromosomes Cancer. 2007 Jan;46(1):37-44. PMID: 17044049

- de Leval L, Rickman DS, Thielen C, Reynies A, Huang YL, Delsol G, Lamant L, Leroy K, Briere J, Molina T, Berger F, Gisselbrecht C, Xerri L, Gaulard P. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood. 2007 Jun 1;109(11):4952-63. PMID: 17284527

- Expression of CXCL13 by neoplastic cells in angioimmunoblastic T-cell lymphoma (AITL): a new diagnostic marker providing evidence that AITL derives from follicular helper T cells. Dupuis J, Boye K, Martin N, Copie-Bergman C, Plonquet A, Fabiani B, Baglin AC, Haioun C, Delfau-Larue MH, Gaulard P. Am J Surg Pathol. 2006 Apr;30(4):490-4. PMID: 16625095

- Ottaviani G, Bueso-Ramos CE, Seilstad K, Medeiros LJ, Manning JT, Jones D. The role of the perifollicular sinus in determining the complex immunoarchitecture of angioimmunoblastic T-cell lymphoma. Am J Surg Pathol. 2004 Dec;28(12):1632-40. PMID: 15577684