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

Disease

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

Note

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.

Etiology

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

Epidemiology

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

Clinics

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.

Cytology

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.

Pathology

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.

    Prognosis

    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

    Note
    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.

    Article Bibliography

    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

    Citation

    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