# Angioimmunoblastic T-cell lymphoma

Angioimmunoblastic T-cell lymphoma (AITL, sometimes misspelled AILT, formerly known as "angioimmunoblastic lymphadenopathy with dysproteinemia"$^{:747}$) 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.

## Signs and symptoms

Patients with AITL 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.

## Causes

AITL was originally thought to be a premalignant condition, termed angioimmunoblastic lymphadenopathy, and this atypical reactive lymphadenopathy carried a risk for transformation into a lymphoma. It is postulated that the originating cell for AITL is a mature (post-thymic) CD4+ T-cell that arises de novo, or that the disease has a premalignant subtype. The Epstein–Barr virus (EBV) is observed in the majority of cases, being identified in the reactive (i.e. non-malignant) B-cells that comprise part of the polymorphous infiltrate of AITL. These EBV+ B cells have numerous non-malignant crippling mutations, often proliferate excessively, and in some cases may transform into EBV+ B cell lymphomas. The other cell types in these infiltrates, including the malignant T$_{FH}$ cells, are EBV negative. While the World Health Organization (2016) has classified these EBV-associated cases as one of the Epstein-Barr virus-associated lymphoproliferative diseases (see EBV+ angioimmunoblastic T cell lymphoma, the role of the virus in the development and progression of EBV+ angioimmunoblastic T cell lymphoma is unclear. Immunodeficiency is also seen with AITL, but it is a sequela and not a predisposing factor.

## Diagnosis
### Laboratory findings

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.

### Lymph node

The normal architecture of a lymph node is partially effaced by a polymorphous infiltrate and residual follicles are commonly seen. 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. A classic morphological finding is the aborization and proliferation of high endothelial venules. Hyperplastic germinal centers and Reed-Sternberg-like cells can also be seen.

### Immunophenotype

AITL 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.

### Molecular findings

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 in 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 AITL cases.

## Treatment

There is a subset of AITL that can remit with immunosuppression with agents like glucocorticoids or methotrexate. Most patients,however, will need combination chemotherapy like CHOP-like chemotherapy backbone- either CHOP alone or CHOP in combination with etoposide(CHOEP). Median response duration is short and median OS is only 15-36 months. Relapsed disease is treated similar to the relapsed PTCL, NOS.[17]

## Epidemiology

The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.