Angioimmunoblastic T-cell Lymphoma

Angioimmunoblastic T-cell Lymphoma

Sa A. Wang, MD

Lymph node involved by angioimmunoblastic T-cell lymphoma (AITL) shows residual follicles, expanded paracortical and interfollicular regions, and open subcapsular (peripheral) sinuses image.

AITL involving lymph node shows increased high endothelial venules (HEV) and a mixed cellular infiltrate. Around the HEV are clusters of neoplastic clear cells.



  • Angioimmunoblastic T-cell lymphoma (AITL)


  • Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)

    • AILD-like (type) T-cell lymphoma

  • Immunoblastic lymphadenopathy


  • Peripheral T-cell lymphoma (PTCL) derived from CD4(+) follicular helper T cells characterized by

    • Lymphadenopathy, systemic disease, and, usually, immunodysregulation and immunodeficiency



  • AITL is tumor of follicular helper T cells

    • Follicular helper T cells upregulate CXCR5 and CXCL13

      • CXCL13 promotes B-cell recruitment through adherence of B cells on high endothelial venules (HEV)

      • CD21(+) follicular dendritic cells expand from HEV

      • Leads to B-cell expansion, plasmacytic differentiation, and hypergammaglobulinemia

Viral Infection

  • EBV(+) B cells are detected in most cases of AITL

    • Most likely secondary event as result of host immunocompromise

  • Human herpesvirus 6B (HHV6B) is also detected by PCR in almost 1/2 of AITL cases

  • EBV and potentially HHV6B may

    • Modulate secretion of cytokines and chemokines or expression of membrane receptors

    • Influence development of tumor microenvironment, favoring disease progression



  • Incidence

    • Rate: 0.5 per 100,000 person years in USA

      • More common in whites than in African-Americans or Asian-Americans

    • Represents 1.2% of all non-Hodgkin lymphomas and 18% of all PTCLs

    • AITL is more common in Europe than in North America or Asia

  • Age

    • Median: 59-65 years in various studies

  • Gender

    • Likely a slight male predominance (but varies in different studies)


  • Subacute or acute systemic illness

  • Advanced stage with generalized lymphadenopathy, hepatomegaly, &/or splenomegaly

  • B symptoms are common (fever, weight loss, night sweats)

  • Skin rash in > 50% of patients

    • Generalized or predominantly truncal maculopapular eruption mimicking inflammatory dermatosis

    • Nodular lesions, plaques, purpura, and urticarial lesions also have been observed

    • Prior to, concurrent with, or following initial diagnosis of AITL

  • Other systemic manifestations

    • Arthralgias or arthritis

    • Pleural effusions, ascites, &/or edema

    • Lung, neurologic, or gastrointestinal involvement

  • Cases of AITL have been reported after administration of antibiotics

    • Most likely, patients with undetected AITL predisposed to infection requiring antibiotic therapy

Laboratory Tests

  • Complete blood cell count

    • Anemia

      • Cryoglobulins or cold agglutinins

      • Positive Coombs test in many patients

    • Hypereosinophilia

    • Lymphopenia (lymphocytosis is rare)

    • Thrombocytopenia

  • Polyclonal hypergammaglobulinemia

    • Hypoalbuminemia

  • ± autoantibodies

    • Rheumatoid factor, anti-nuclear factor, anti-smooth muscle

  • Elevated erythrocyte sedimentation rate

  • Elevated serum lactate dehydrogenase and β2-microglobulin levels


  • No consensus on optimal therapeutic regimen

  • For medically eligible patients, combined chemotherapy followed by autologous hematopoietic cell transplantation after achieving remission

  • For nontransplant candidates, combined chemotherapy

  • Steroids have role for patients who are not candidates for chemotherapy

  • Novel, investigational therapies are needed for patients with AITL


  • Aggressive, with median survival of < 3 years

  • ˜ 30% of patients are long-term survivors

  • Adverse prognostic factors

    • Male sex, mediastinal lymphadenopathy, and anemia adversely affect overall survival

    • Overall immune status also influences survival

  • Histological features of AITL do not correlate with prognosis


Radiographic Findings

  • Generalized lymphadenopathy, organ involvement, body effusions

    • Cannot distinguish AITL from other lymphoma types with disseminated disease


Histologic Features

  • Lymph node

    • Partial or complete effacement of architecture; perinodal infiltration common

      • Paracortical distribution of neoplasm

      • Peripheral sinuses in lymph node cortex are often patent

    • Neoplastic cells are small- to medium-sized, with clear to pale cytoplasm, distinct cell membranes, and minimal atypia

      • Tumor cells often form small clusters around follicles and HEV

    • Background cells are polymorphous

      • Variable numbers of small reactive lymphocytes, eosinophils, plasma cells, and histiocytes

      • ± immunoblasts of B-cell lineage; number is variable and can be prominent

      • ± HRS-like cells of B-cell lineage; usually EBV(+)

    • Marked proliferation of arborizing high endothelial venules (HEV)

    • Increased proliferation of follicular dendritic cells (FDC), usually surrounding HEV

    • 3 patterns in lymph node have been described

      • I: Architecture is partially preserved and hyperplastic, or normal follicles are present

      • II: Architecture is mostly effaced with residual follicles present; ± follicles disrupted or irregular

      • III: Architecture is completely replaced; ± few regressed (“burned out”) follicles

  • Bone marrow

    • Nodular or interstitial aggregates in paratrabecular or nonparatrabecular distribution

      • Neoplastic cells are often small; ± clear cytoplasm; can be difficult to identify

      • Reactive cells include plasma cells, eosinophils, histiocytes, and B cells

      • Aggregates are associated with blood vessel proliferation

      • ± EBV(+) cells

    • Uninvolved bone marrow ± reactive changes associated with AITL

      • Erythroid hyperplasia, polyclonal plasmacytosis, eosinophilia, fibrosis, or hemophagocytosis

  • Peripheral blood

    • Lymphocytosis is uncommon

    • ± atypical lymphocytes or activated lymphocytes (so-called immunocytes)

    • CD10(+) T cells have been shown in many patients by flow cytometric immunophenotyping

  • Skin

    • Changes are variable, may not always result from direct tumor infiltration

      • Changes can range from nonspecific, mild perivascular dermal lymphocytic infiltrate to, more rarely, overt lymphoma

  • Body effusions

    • Nonneoplastic in nature and their cause is poorly understood

    • Mixture of small lymphocytes, histiocytes, ± eosinophils

  • Morphological variants of AITL

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Angioimmunoblastic T-cell Lymphoma

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