T-cell Large Granular Lymphocytic Leukemia

T-cell Large Granular Lymphocytic Leukemia

Kaaren K. Reichard, MD

Classic appearance of a large granular lymphocyte (LGL) is shown. LGLs constitute up to 15% of circulating white blood cells normally. Immunophenotyping shows that most are cytotoxic T cells.

CD3 immunostaining shows a marked increase in mature T cells in a case of T-LGL leukemia. The pattern of involvement is typically interstitial/intrasinusoidal and often morphologically occult.



  • T-cell large granular lymphocytic leukemia (T-LGL leukemia)


  • Persistent clonal proliferation of T-cell large granular lymphocytes (T-LGLs)



  • Chronic antigenic stimulation resulting in proliferation of T-cell large granular lymphocytes (T-LGLs)

    • Exogenous antigens such as HTLV

    • Endogenous autoantigens

  • Inhibition of apoptosis resulting in accumulation of T-LGLs

    • Dysregulation of FAS/FAS-L

Infectious Agents

  • Role of retroviral infection unclear

  • Most patients do not show evidence of HTLV-I or HTLV-II infection

  • Reactivity against small peptide derived from an HTLV-I envelope protein has been reported

Etiology of Neutropenia

  • FAS/FAS-L-induced premature apoptosis of granulocytic precursors



  • Incidence

    • Comprises 2-3% of chronic lymphocytic leukemias

  • Age

    • Median age: 60 years

    • Predominantly affects adults

  • Gender

    • No gender predilection


  • Peripheral blood (PB)

  • Bone marrow (BM)

  • Spleen

  • Liver


  • Asymptomatic

    • Incidental discovery of T-LGL lymphocytosis

  • Asymptomatic

    • Cytopenias

      • No clinically appreciated effects

    • Rheumatoid arthritis or autoimmune disorder (25-35% of patients)

    • Splenomegaly (20-50% of patients)

  • Symptomatic

    • Development of cytopenias

      • Neutropenia

      • Thrombocytopenia

      • Anemia: May be due to red cell aplasia

    • Development of recurrent infections

      • Often bacterial

      • Mucocutaneous

    • Splenomegaly

    • Systemic symptoms

  • LGL lymphocytosis: LGLs generally > 2 × 109/L

Laboratory Tests

  • Clinical examination

  • Complete blood cell count with differential

  • PB examination

  • BM examination if needed

  • Flow cytometry of PB &/or BM

  • T-cell receptor clonality studies

Natural History

  • Clinically heterogeneous

  • Some spontaneous regressions

  • Association with immune disorders

  • High proportion of patients will require treatment at some point


  • Asymptomatic

    • Careful observation

  • Symptomatic

    • Methotrexate or cyclophosphamide or cyclosporine A

      • Treatment should be continued for at least 4 months to assess response

    • Corticosteroids

      • As monotherapy, not very effective long-term

      • Rapid improvements in symptoms/cytopenias if used in conjunction with methotrexate, cyclophosphamide, cyclosporine A

    • Prophylactic use of antibiotics if severe neutropenia

    • Hematopoietic growth factors

      • GM-CSF or G-CSF for neutropenia

      • Erythropoietin (EPO) for anemia

    • Clinical trial

      • As available

    • Progressive disease

      • Nucleoside analogues

      • Alemtuzumab: Anti-CD25 monoclonal antibody

      • Hematopoietic stem cell transplantation


  • Generally indolent

  • Related to control of cytopenias and associated symptoms


Peripheral Blood

  • LGL lymphocytosis

    • LGLs generally > 2 × 109/L

    • Occasional cases LGLs < 2 × 109/L

  • Circulating T-LGLs

    • Intermediate size

    • Round/slightly indented nucleus

    • Inconspicuous nucleoli

    • Abundant pale cytoplasm

    • Cytoplasmic azurophilic granules

  • Variable degrees/types of cytopenias

  • Generally unremarkable red blood cell, platelet, and myeloid morphology

Jun 13, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on T-cell Large Granular Lymphocytic Leukemia
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