T-cell large granular lymphocyte (LGL)

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T-cell large granular lymphocyte (LGL) leukemia is caused by a clonal proliferation of cytotoxic (CD8+) T cells and is characterized clinically by neutropenia, anemia and/or thrombocytopenia, and a modest lymphocytosis.LGL with abundant cytoplasm and fine or coarse azurophilic granules. It can occur in association with multiple autoimmune conditions.T-LGL involves the PB, BM, liver, spleen.

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Immunophenotyping:

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CD3+, TCRαβ+, CD4-, CD8+ (Common type)

1.CD3+, TCR+, CD4+, CD8-(Rare type)

2.CD3+, TCR+, CD4+ and CD8+(Rare type)

3. CD3+, TCRgd+ (CD4 and CD8 expression not well defined)(Rare type)

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CD11b, CD56 and CD57 are variably expressed. TIA-1 is usually positive.

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References:

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• Dhodapkar MV, Li CY, Lust JA, et al. Clinical spectrum ofclonal proliferations of T-large granular lymphocytes: a T-cell clonopathy of undetermined significance? Blood.1994;84:1620-1627.

• Bigouret V, Hoffmann T, Arlettaz L, et al. Monoclonal T-cell expansions in asymptomatic individuals and in patients with large granular leukemia consist of cytotoxic effector T cells expressing the activating CD94:NKG2C/E and NKD2D killer cell receptors Blood.2003;101:3198-3204.

• Lamy T, Loughran TP Jr. Clinical features of large granularlymphocyte leukemia.Semin Hematol.2003;40:185-195.

• Morice WG, Kurtin PJ, Tefferi A, et al. Distinct bone marrowfindings in T-cell granular lymphocytic leukemia revealed byparaffin section immunoperoxidase stains for CD8, TIA-1, andgranzyme B.Blood.2002;99:268-274.

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• Saunthararajah Y, Molldrem JL, Rivera M, et al. Coincidentmyelodysplastic syndrome and T-cell large granularlymphocytic disease: clinical and pathophysiological features.Br J Haematol.2001;112:195-200.

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• Morice WG, Kurtin PJ, Leibson PJ, et al. Demonstration ofaberrant T-cell and natural killer-cell antigen expression in allcases of granular lymphocytic leukaemia.Br J Haematol.2003;120:1026-1036.

• Pittet MJ, Speiser DE, Valmori D, et al. Cutting edge: cytolyticeffector function in human circulating CD8+ T cells closelycorrelates with CD56 surface expression.J Immunol.2000;164:1148-1152.

• Brenchley JM, Karandikar NJ, Betts MR, et al. Expression ofCD57 defines replicative senescence and antigen-inducedapoptotic death of CD8+ T cells. Blood.2003;101:2711-2720.

• Posnett DN, Sinha R, Kabak S, et al. Clonal populations ofT cells in normal elderly humans: the T cell equivalent to“benign monoclonal gammapathy.”J Exp Med.1994;179:609-618.

• Hoffmann T, De Libero G, Colonna M, et al. Naturalkiller–type receptors for HLA class I antigens are clonallyexpressed in lymphoproliferative disorders of natural killer andT-cell type.Br J Haematol.2000;110:525-536.

• Moretta A, Biassoni R, Bottino C, et al. Major histocompatibility complex class I–specific receptors onhuman natural killer and T lymphocytes. Immunol Rev.1997;155:105-117