Lymphoma and plasma cell neoplasms
T / NK cell disorders
Angioimmunoblastic T cell lymphoma

Author: Guang (Geoff) Yang, M.D., Ph.D. (see Authors page)
Editor: Fouad Abdelhalim, M.D.

Revised: 20 June 2017, last major update June 2017

Copyright: (c) 2001-2017, PathologyOutlines.com, Inc.

PubMed search: angioimmunoblastic T cell [title] lymphoma

Cite this page: Angioimmunoblastic T cell lymphoma. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lymphomanonBAITL.html. Accessed November 18th, 2017.
Definition / general
  • Angioimmunoblastic T cell lymphoma (AITL) is a peripheral T cell lymphoma characterized by systemic disease, a polymorphous infiltrate involving lymph nodes, and a prominent proliferation of high endothelial venules and follicular dendritic cells (WHO 2008)
  • According to the 2016 revision of the World Health Organization classification of lymphoid neoplasms, AITL now resides under the umbrella category of nodal T cell lymphomas with T follicular helper (TFH) phenotype (Blood 2016;127:2375)
Essential features
  • Nodal architecture partially to completely effaced
  • Follicular dendritic cell proliferation
  • Prominent high endothelial venules
  • CD4+, CD10+, PD1+, CXCL13+ T cell immunoblasts, CD21+ FDCs, EBV+ B cells
  • TCR and IGH gene rearrangements
Terminology
  • Originally described in 1974 as a nonneoplastic abnormal immune reaction (Lancet 1974;1:1070)
  • Formerly termed angioimmunoblastic lymphadenopathy with dysproteinemia, immunoblastic lymphadenopathy, lymphogranulomatous X and immunodysplastic disease (Hsi: Hematopathology, Second Edition, 2012)
  • Acknowledged entity since the 1994 Revised European American Lymphoma (REAL) Classification (Blood 1994;84:1361)
Epidemiology
Sites
Etiology
  • The neoplastic cell in AITL is a follicular T helper (TFH) cell
  • Cellular components of the microenvironment include high endothelial venules (HEVs), EBV+ B cells and TFH
  • Dysregulation of the TFH cell leads to germinal center anarchy and subsequent development of AITL
  • The B cell activation leads to autoimmune hemolytic anemia (AIHA) and hypergammaglobulinemia (Blood 2017;129:1095)
  • Described mutations in AITL: TET2 , DNMT3A , IDH2 , RHOA , CD28 , PLCG1 and TNFRSF21 (DR6) (Hematol Oncol Clin North Am 2017;31:223, Oncotarget 2017;8:17763)
Clinical features
Diagnosis
  • Best made by excisional biopsy, usually a lymph node, interpreted withi clinical presentation
  • Testing for clonal T cell receptor rearrangement can be helpful (eMedicine)
Laboratory
  • Polyclonal hypergammaglobulinemia and autoimmune hemolytic anemia (Hsi: Hematopathology, Second Edition, 2012)
  • Eosinophilia, thrombocytopenia, lymphopenia, elevated lactate dehydrogenase serum levels, elevated erythrocyte sedimentation rate and an array of autoantibodies (rheumatoid factor, antinuclear antibody, anti-smooth muscle antibody) (Semin Hematol 2014;51:52)
Prognostic factors
Case reports
Treatment
  • First line: anthracycline containing regimens
  • Consolidative autologous transplantation
  • Romidepsin, belinostat, brentuximab, vedotin, lenalidomide seem active in pretreated patients (Hematol Oncol Clin North Am 2017;31:223)
Clinical images

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Violaceous erythema and bullae of the foot

Macular erythema on the trunk

Confluent lesions over the back

Microscopic (histologic) description
  • Lymph nodes:
    • Partial effacement of lymphonodular architecture, often with perinodal infiltration but with preservation of subcapsular and trabecular sinuses
    • Prominent arborizing high endothelial venules with thickened, hyalinized PAS+ walls surrounded by CD21+ follicular dendritic cells and irregular homogenous eosinophilic material
    • Burnt out germinal centers with increased follicular dendritic cell meshworks (mediated through expression of CXCL13 by neoplastic follicular helper T cells)
    • Predominantly paracortical aggregates of polymorphic small to medium sized cells with clear / pale cytoplasm, distinct cell membranes and minimal cytologic atypia
    • Small clusters of neoplastic cells around follicles and high endothelial venules, variable numbers of small reactive lymphocytes, eosinophils, plasma cells, histiocytes
    • Paracortical expansion of B immunoblasts linked to the functional properties of neoplastic follicular helper T cells
    • Three different histologic patterns described, I - III, with increasing degrees of architectural effacement, commonly coexisting in the same specimen, arbitrary cutoffs
  • Bone marrow:
    • Focal or diffuse marrow involvement
    • Focal lesions have indistinct margins
    • Contain polymorphous infiltrate of lymphocytes, immunoblasts, plasma cells, histiocytes, eosinophils and neutrophils
    • Often vascular proliferation with prominent endothelial cells and fibroblasts
    • Perivascular clustering of neoplastic clear cells in 41%
    • Variable epithelioid histiocytes
    • Usually no amorphous PAS+ material (found in nodal lesions)
    • Uninvolved marrow may be hypercellular
  • Peripheral blood:
    • Reactive lymphocytes, immunoblasts, immunocytes, increased eosinophils, various cytopenias, rouleaux
    • May also see circulating lymphoma cells
  • Skin:
Microscopic (histologic) images

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Various images



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H&E 20x;

40x

Various images

Lymph node



CD3+

CD4 weak

BCL6+

Various images

Cytology description
  • Small to large cells with moderate to faint basophilic cytoplasm without azurophilic granules and sometimes with microvacuoles, often irregular or indented nuclei, moderately condensed chromatin
Cytology images

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Peripheral blood: atypical lymphocytes

Positive stains
Negative stains
Flow cytometry Images

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Immunophenotypic features

Electron microscopy description
  • Lymphocytes with cytoplasmic vacuoles thought to correspond to neoplastic cells
  • High endothelial venules: swollen endothelial cells with walls thickened by basement membrane-like material and immunoglobulin deposition
  • Intercellular collagen and immunoglobulins correspond to the eosinophilic PAS+ material
Molecular / cytogenetics description
Differential diagnosis
Board review question #1
Follicular dendritic cell proliferation and prominent high endothelial venules are classic features of which of the following lymphoma/condition?

  1. Angioimmunoblastic T cell lymphoma
  2. Atypical T zone hyperplasia
  3. Classical Hodgkin lymphoma
  4. Peripheral T cell lymphoma, not otherwise specified
Board review answer #1
A. Follicular dendritic cell proliferation and prominent high endothelial venules are classic features of angioimmunoblastic T cell lymphoma.

  1. Incorrect: these two features are usually absent in atypical T zone hyperplasia.
  2. Incorrect: these two features are usually absent in classical Hodgkin lymphoma.
  3. Incorrect: although high endothelial venules can occasionally be seen in peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), follicular dendritic cell proliferation is usually absent in PTCL, NOS.

(Hsi: Hematopathology, Second Edition, 2012)