T-cell large granular lymphocyte leukaemia

2002-08-01   KF Wong 

1.Department of Pathology, Queen Elizabeth Hospital, 30 Gascoigne Road, Kowloon, Hong Kong SAR, China

Clinics and Pathology


T-cell large granular lymphocyte leukaemia (T-LGL)


T-LGL is also called T-cell chronic lymphocytic leukaemia, Tgamma lymphoproliferative disorder and large granular lymphocytosis.

Phenotype stem cell origin

Clonal proliferation of CD3+ CD4- CD8+ CD56± CD57+ TCRab+ mature T cells with rearranged TCRab genes; rarely, variable expression of both CD4 and CD8 or expression of TCRgd.


Sometimes associated with B cell chronic lymphoproliferative disorder such as hairy cell leukaemia and chronic lymphocytic leukaemia; rarely may follow solid organ transplantation.


2-5% of all chronic lymphoproliferative disorders in the West, and 5-6% in the Chinese population.


Often asymptomatic, and incidentally found to have lymphocytosis and moderate splenomegaly; frequently accompanied by severe neutropenia (sometimes with recurrent infections); anaemia due to red cell aplasia, and sometimes thrombocytopenia; associated with immune mediated disturbances such as cytopenia, rheumatoid arthritis, Sjogrens syndrome, circulating autoantibodies and immune complexes, and hypergammaglobulinaemia; indolent clinical course.


Large granular lymphocytes (LGLs) with the nucleus of a small lymphocyte but abundant cytoplasm and fine or coarse azurophilic granules; ultrastructural examination may reveal characteristic parallel tubular arrays; the LGLs are often >2x109/L.


Involvement of blood, bone marrow, liver and spleen; lymphadenopathy is very rare; not associated with EBV or HTLV I/II.
  • In the bone marrow, the infiltration is usually interstitial with occasional focal aggregates; in some patients, the involvement may be minimal and not readily detectable on histologic sections; the lymphocytes are small to medium-sized with abundant cytoplasm, and the granules are not apparent in histologic sections.
  • In the spleen, the red pulp is expanded; the infiltrate is predominantly sinusoidal but may also involve the pulp cords; in the liver, there is a sinusoidal pattern of infiltration with portal involvement in severe cases; in the lymph node, the infiltrate primarily involves the paracortical regions and medullary cord
  • Treatment

    Cyclosporin A (particularly for pure red cell aplasia and other immune mediated disturbances); other treatments include methotrexate, cyclophosphamide, chlorambucil, corticosteroids and deoxycoformycin (pentostatin) with variable success; and splenectomy for grossly enlarged and incapacitating splenomegaly.


    An indolent disease, with morbidity mostly attributed to neutropenia or anaemia; mortality is uncommon; an aggressive form of T-LGL with dysregulated expression of Fas ligand has been reported; large cell transformation has also rarely been described.

    Genes Involved and Proteins

    As with other T-cell lymphoproliferative disorders, T-LGL exhibits clonal rearrangement of the TCR genes; in most cases, the TCRA TCRD genes are rearranged, but rarely, the TCRG gene is rearranged while the TCRB gene is in germline configuration.
    Unlike other T-cell malignancies, karyotypic aberrations in T-LGL rarely involve the TCR gene loci; so far, only one case each with possible involvement of the TCRG gene at 7p14-p15 in an inv(7)(p15q22) and the TCR A/D genes at 14q11 in an inv(14)(q11q32) has been described.


    Pubmed IDLast YearTitleAuthors
    26614081989The pathology of large granular lymphocyte leukemia.Agnarsson BA et al
    86394391996Cyclosporine A alleviates severe anaemia associated with refractory large granular lymphocytic leukaemia and chronic natural killer cell lymphocytosis.Bible KC et al
    76048141995T-cell large granular lymphocytic leukemia following orthotopic liver transplantation.Feher O et al
    96338951998Large granular lymphocyte leukaemia occurring after renal transplantation.Gentile TC et al
    114353212001Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes.Go RS et al
    99300711998Association of pure red cell aplasia with T large granular lymphocyte leukaemia.Kwong YL et al
    86399221996Pure red cell aplasia: association with large granular lymphocyte leukemia and the prognostic value of cytogenetic abnormalities.Lacy MQ et al
    107922742000Clinicopathological features of aggressive large granular lymphocyte leukaemia resemble Fas ligand transgenic mice.Lamy T et al
    107418981999Current concepts: large granular lymphocyte leukemia.Lamy T et al
    83242141993Clonal diseases of large granular lymphocytes.Loughran TP Jr et al
    125471642002Deletion 6q as a recurrent chromosomal aberration in T-cell large granular lymphocyte leukemia.Man C et al
    28409881988Hairy cell leukemia associated with large granular lymphocyte leukemia: immunologic and genomic study, effect of interferon treatment.Marolleau JP et al
    118438122001Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma.Matutes E et al
    117084332001Sjögren's syndrome associated T cell large granular lymphocyte leukemia: a possible common etiopathogenesis.Molad Y et al
    94023221997Clonal populations of T-cells in patients with B-cell malignancies.Moss PA et al
    92643851997The human T-cell lymphotropic viruses types I/II are not involved in T prolymphocytic leukemia and large granular lymphocytic leukemia.Pawson R et al
    118492172002Chromosomal abnormalities in T-cell large granular lymphocyte leukaemia: report of two cases and review of the literature.Wong KF et al
    107217732000Development of lymphoproliferative disorder of granular lymphocytes in association with hairy cell leukemia.Xie XY et al


    KF Wong

    T-cell large granular lymphocyte leukaemia

    Atlas Genet Cytogenet Oncol Haematol. 2002-08-01

    Online version: http://atlasgeneticsoncology.org/haematological/2098/t-cell-large-granular-lymphocyte-leukaemia

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