Flow Cytometry Analysis Reveals a Wide Cytologic and Immunophenotypic Spectrum of Peripheral B Lymphocytes in Angioimmunoblastic T-Cell Lymphoma

Pathobiology. 2023;90(3):187-198. doi: 10.1159/000526284. Epub 2022 Nov 24.

Abstract

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma commonly associated with B-cell dysregulation. Correlations involving B-cell dysregulation and clinicopathological features remain unclear.

Methods: We prospectively collected blood samples from 11 AITL patients and 17 healthy controls. The percentages of B-cell subpopulations and lymphocytes with IL-21 production were assessed using flow cytometry. Peripheral blood lymphocyte morphology was evaluated microscopically.

Results: Six of 11 (54.5%) patients presented with polyclonal hypergammaglobulinemia. Three of 11 (27.3%) tumor biopsies showed monoclonal immunoglobulin gene rearrangement. The patients exhibited significantly lower levels of naive (p < 0.001) and class-switched (p < 0.001) B cells than controls. The percentages of IgD-CD27- B cells (p = 0.007) and antibody-secreting cells (ASCs) (p = 0.001) were increased. Blood smears revealed atypical lymphocytes and immature plasma cells with morphological diversity. In comparison to normal controls, IL-21 production significantly increased in CD4+ (p < 0.001) and CD8+ (p = 0.020) T cells. B-cell clonality, RHOA G17V mutation, and the presence of sheets of clear cells and immature/mature plasma cells in lymph nodes were significantly associated with percentages of class-switched B cells and ASCs. The patients with circulating EBV DNA had a lower percentage of naive B cells (p = 0.009).

Conclusions: Our results demonstrated a wide spectrum of peripheral B-cell morphologies and immunophenotypes of peripheral B cells in AITL. These findings correspond to dysregulated B-cell immunity and heterogeneous clinicopathological features.

Keywords: AITL; B-cell subpopulations; Flow cytometry; IL-21.

MeSH terms

  • B-Lymphocytes / pathology
  • Flow Cytometry
  • Humans
  • Immunoblastic Lymphadenopathy* / diagnosis
  • Immunoblastic Lymphadenopathy* / genetics
  • Immunoblastic Lymphadenopathy* / pathology
  • Lymphoma, T-Cell* / diagnosis
  • Lymphoma, T-Cell* / genetics
  • Lymphoma, T-Cell* / pathology
  • Lymphoma, T-Cell, Peripheral* / pathology