Lymphoma & related disorders

Mature T/NK cell disorders

T follicular helper phenotype

Angioimmunoblastic T cell lymphoma



Last author update: 13 July 2022
Last staff update: 13 July 2022

Copyright: 2001-2022, PathologyOutlines.com, Inc.

PubMed search: Angioimmunoblastic T cell lymphoma

Mario L. Marques-Piubelli, M.D.
Roberto N. Miranda, M.D.
Page views in 2021: 15,905
Page views in 2022 to date: 10,279
Cite this page: Marques-Piubelli ML, Miranda RN. Angioimmunoblastic T cell lymphoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBAITL.html. Accessed August 15th, 2022.
Definition / general
Essential features
Terminology
  • Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD)
  • Immunoblastic lymphadenopathy
  • Lymphogranulomatosis X
ICD coding
  • ICD-O: 9705/3 - angioimmunoblastic T cell lymphoma
  • ICD-10: C86.5 - angioimmunoblastic T cell lymphoma
Epidemiology
Sites
Pathophysiology
  • T follicular helper (TFH) cells are essential checkpoints for the B cell activation and differentiation from centroblast to centrocytes; consequently these cells become either plasma cells or memory B cells (Blood 2017;129:1095)
    • TFH tolerance is an important mechanism in the prevention of autoimmune diseases
    • Dysregulation of TFH checkpoints may cause a germinal center anarchy and consequent AITL
Etiology
  • Somatic mutations (Blood 2017;129:1095, Nat Genet 2014;46:371):
    • TET2, DNMT3A, IDH2-R172 and RHOA
  • Immunodysregulation (Blood 2017;129:1095, Leukemia 2022;36:165)
    • Upregulation of TFH cells promotes a high differentiation of B cells, plasmacytic differentiation and hypergammaglobulinemia
      • B cells of the tumor microenvironment decrease the expression of CD73 and CXCR5
    • Expansion of a distinct population of CD8+ T cells with exhausted phenotype and upregulation of the chemokines XCL2 and XCL1
  • Possible relationship to Epstein-Barr virus (EBV) with disease progression (Blood 2017;129:1095, Am J Surg Pathol 2016;40:335)
    • B cells in AITL usually show active EBV infection
Clinical features
Diagnosis
Laboratory
Radiology description
  • CT usually shows low bulky disease, which has variable uptake values on PET (Blood 2017;129:1095)
Prognostic factors
Case reports
Treatment
  • Single agent oral therapies or intensive chemotherapy combination followed by autologous stem cell transplantation (Blood 2017;129:1095, J Clin Oncol 2009;27:3951, Leukemia 2020;34:2592, Blood 2008;111:4463, J Oncol Pract 2019;15:137)
    • Good response but short remission duration
    • No gold standard chemotherapy, usually anthracycline based regimen
      • CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)
        • 53% of complete remission in up front setting
      • CHOEP (CHOP + etoposide)
        • 51% of complete remission in up front setting
      • Romidepsin + CHOP
        • 51% of complete remission in relapsed / refractory setting
      • Bevacizumab + CHOP
      • R-CHOP (rituximab + CHOP)
      • Alemtuzumab + CHOP
      • ACVBP (doxorubicin, cyclophosphamide, vindestine, bleomycin, prednisone)
      • ACVBP (doxorubicin, cyclophaphamide, vindesine, bleomycin, prednisone)
      • Bortezomibe + ACVBP
      • mBACOD (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone)
      • PEGS (cisplatinum, etoposide, gemcitabine, methylprednisolone)
      • ICE (iphosphamide, carboplatin, etoposide), DHAP (dexamethasone, cytarabine, cisplatinum) and ESHAP (etoposide, methylprednisolone, cisplatinum, cytarabine)
        • Relapsed / refractory setting
    • Single agents
      • Used in a relapsed / refractory setting
      • Pralatrexate
      • Romidepsin
      • Brentuximab vedotin
      • Belinostat
      • Bendamustine
      • Lenalidomide
      • Hypomethylating agents
        • Azacitidine and decitabine
          • Counterbalance the DNA hypermethylation caused by TET2 and IDH2 mutation
    • Consolidation with stem cell transplantation
      • Able to achieve 70% of complete remission and progression free survival of 42% in 2 years
      • Complete remission patients have better survival compared with those with partial remission (PR)
      • Graft versus host disease (GVHD) may affect up to 60%
Microscopic (histologic) description
  • Lymph node (Leuk Lymphoma 2016;57:2804, Blood 2017;129:1095, Histopathology 2014;64:171, Hum Pathol 2010;41:79, Mod Pathol 2009;22:753, Am J Surg Pathol 2007;31:1077, Leukemia 2020;34:2592)
    • Partial or complete architecture effacement
      • Pattern I: architecture partially preserved and hyperplastic follicles with tingible body macrophages and indistinct mantle zones
      • Pattern II: architecture mostly preserved with residual follicles
      • Pattern III: architecture completely effaced without residual follicles
    • AITL cells are the minority population and are located adjacent to high endothelial venules (HEV) or around follicles
      • Small to intermediate size, clear cytoplasm and minimal atypia
        • Clear cytoplasm in ~30% of cases
    • Polymorphous inflammatory background composed of reactive lymphocytes, histiocytes, eosinophils, plasma cells, reactive B cells, Reed-Sternberg-like cells, immunoblasts and follicular dendritic cells
  • Peripheral blood (Hum Pathol 2010;41:79, Leukemia 2006;20:296, Medicine (Baltimore) 2007;86:282)
    • Limited evaluation
    • Lymphopenia
    • Cases with pronounced involvement usually show polymorphic lymphoid population composed of few atypical cells, lymphoplasmacytic, immunoblasts, granular lymphocytes and plasma cells; neoplastic cells are small to large sized lymphocytes with regular or slightly indented nuclei, moderated condensed chromatin, small or indistinct nucleoli and abundant basophilic cytoplasm
    • Cases with hypergammaglobulinemia may show rouleaux formation
  • Bone marrow (Hum Pathol 2010;41:79, Am J Clin Pathol 2007;128:854, Leukemia 2006;20:296, Medicine (Baltimore) 2007;86:282)
    • Bone marrow aspirates are not optimal for diagnosis: very few or absent atypical lymphocytes
    • Usually multifocal and poorly defined nodular pattern in core biopsies
      • Rare cases of paratrabecular pattern
      • Minority of cases present with HEV, stromal edema or patent sinusoids
    • Heterogeneous cellular background
    • Hemophagocytic syndrome is rare
    • Reticulin stain is usually disrupted in lymphoid aggregates
  • Skin (Medicine (Baltimore) 2007;86:282, Am J Surg Pathol 2007;31:1068)
    • Broad histological presentation
      • Histologic picture of vasculitis is more common
      • Band-like subepidermal, perivascular, periadnexial or diffuse infiltrate
      • Epidermotropism not present
Microscopic (histologic) images

Contributed by Roberto N. Miranda, M.D.
Pattern I: partial nodal involvement

Pattern I: partial nodal involvement

Pattern III: complete effacement of nodal architecture

Pattern III: complete effacement

Pattern III: capsular involvement

Pattern III: capsular involvement

Polymorphic infiltrate

Polymorphic infiltrate

Polymorphic infiltrate with eosinophilia

Polymorphic infiltrate with eosinophilia


Bone marrow involvement

Bone marrow involvement

Diffuse reactivity with CD3 Diffuse reactivity with CD3

Diffuse reactivity with CD3

CD20

CD20

CD21, pattern I

CD21, pattern I


CD21, pattern III

CD21, pattern III

PD-1 positivity

PD-1 positivity

CXCL13 positivity

CXCL13 positivity

CD10 in small and intermediate size lymphoma cells

CD10 in small and intermediate size lymphoma cells

CD30 positivity

CD30 positivity


Epstein-Barr virus (EBER) reactivity

Epstein-Barr virus (EBER) reactivity

Proliferation marker Ki67

Proliferation marker Ki67

CD3 reactivity in bone marrow

CD3 reactivity in bone marrow

CD10 reactivity

CD10 reactivity

Positive stains
Negative stains
Flow cytometry description
Molecular / cytogenetics description
Sample pathology report
  • Axillary lymph node, excisional biopsy:
    • Angioimmunoblastic T cell lymphoma (see comment)
    • Comment: According to clinical notes, patient is a 65 year old man with generalized lymphadenopathy, B symptoms, splenomegaly, anemia and thrombocytopenia. The peripheral blood shows anemia and thrombocytopenia. H&E sections show a complete effacement of the lymph node architecture by a diffuse and polymorphic infiltrate. Paracortical areas show increased vascularity with an arborizing pattern and the endothelial cells are prominent. The polymorphic infiltrate is composed of small to intermediate size atypical cells with slight nuclear irregular contours admixed with plasma cells, Reed-Sternberg-like cells, neutrophils and reactive small lymphocytes.
    • Immunohistochemical studies show a neoplastic population positive for CD2, CD3, CD4, CD5, CXCL13, CD10 and PD-1. The aberrant cells are negative for CD7, CD8, CD20, CD30, CD138 and ALK1. Kappa and lambda highlight polytypic plasma cells. The CD21 marker highlights follicular dendritic cell meshworks, which appear expanded around clusters of vessels. Epstein-Barr virus encoded small RNAs (EBER) in situ hybridization was positive in scattered large cells. Concurrent flow cytometry immunophenotype showed an aberrant T cell population positive for CD2, CD4, CD5 and CD10. The aberrant cells are negative for sCD3, CD7, CD8, CD19, CD20, CD56, TCRαβ (partial loss) and TCRγδ. A next generation sequencing panel demonstrated TET2, DNMT3, RHOA and IDH2 mutations. Polymerase chain reaction for Ig heavy chain (IGH) and T cell receptor gamma (TRG) were germline and T cell receptor beta (TRB) was monoclonal.
Differential diagnosis
Board review style question #1

What is the characteristic immunophenotype of angioimmunoblastic T cell lymphoma (AITL)?

  1. εCD3+ / CD4+ / CD7+ / CD8+ / CXCL13+ / PD-1-
  2. εCD3+ / CD4+ / CD7- / CD8- / CXCL13+ / PD-1+
  3. εCD3+ / CD4- / CD7- / CD8+ / CXCL13+ / PD-1+
  4. εCD3+ / CD4+ / CD7+ / CD8- / CXCL13- / PD-1+
Board review style answer #1
B. εCD3+ / CD4+ / CD7- / CD8- / CXCL13+ / PD-1+. Angioimmunoblastic T cell lymphoma (AITL) cells are usually positive for εCD3, CD4 and TFH markers (e.g. CXCL13, PD-1, CD10 and ICOS). Loss of CD7 is also observed.

Comment Here

Reference: Angioimmunoblastic T cell lymphoma
Board review style question #2
Which of the following is true about angioimmunoblastic T cell lymphoma (AITL)?

  1. Histologic pattern I is characterized by a complete effacement of the lymph node architecture
  2. Peripheral blood involvement is common
  3. The most common clinical presentation is localized disease and type A symptoms
  4. The most common mutations are TET2, DNMT3A, IDH2 and RHOA
Board review style answer #2
D. The most common mutations in angioimmunoblastic T cell lymphoma (AITL) are TET2, DNMT3A, IDH2 and RHOA. There are 3 histological patterns in the lymph node: pattern I (architecture partially preserved and hyperplastic), pattern II (architecture mostly effaced but residual follicles can be identified) and pattern III (architecture completely effaced). Peripheral blood is involved in a subset of cases. The most common clinical presentation is with advanced stage disease and type B symptoms. The most common mutations are TET2, DNMT3A, IDH2 and RHOA.

Comment Here

Reference: Angioimmunoblastic T cell lymphoma
Back to top
Image 01 Image 02