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T-cell large granular lymphocytic leukaemia (T-LGLL) and chronic lymphoproliferative disorder of NK cells (CLPD-NK) are two closely related diseases that share clinical, cytological and molecular genetic features. T-LGLL is derived from the clonal expansion of a cytotoxic effector memory T cell and is included as a definitive entity in the WHO classification [1]. Although the pathogenesis is largely unknown, it is thought to be the result of chronic persistent antigen stimulation of a T cell with a failure to undergo apoptosis. CLPD-NK is derived from mature natural killer cells and is considered as a provisional entity in the WHO classification [2]. There is no relationship to human lymphotropic viruses 1 or 2 in T-LGLL [3] or to Epstein–Barr virus in CLPD-NK.

Clinical features

Some patients are asymptomatic and the diagnosis is incidental. About a half to a third of patients present with symptoms resulting from cytopenia, for example infection as a result of neutropenia. B symptoms are rare. T-LGLL, but not CLPD-NK, is associated with rheumatoid arthritis and other autoimmune diseases. The two disorders can follow or be associated with other haematological diseases such as myelodysplastic syndromes, B-cell lymphomas treated with immunochemotherapy, monoclonal gammopathy of undetermined significance and chronic myeloid leukaemia under dasatinib therapy [4–7]. Splenomegaly is common; hepatomegaly and skin lesions are present in a few patients but lymphadenopathy is quite uncommon. Transformation to high-grade lymphoma is very rare [8] (Figure 19.1).

Figure 19.1

Peripheral blood film (PB) from a patient with large granular lymphocytic leukaemia of T lineage (T-LGLL) that underwent transformation to a large cell lymphoma in a lymph node, bone marrow and blood showing a large cell with deeply basophilic cytoplasm and fine granulation. Romanowsky stain, ×100 objective.

Haematological and pathological features

There is an increase in circulating large granular lymphocytes but the extent of this is very variable. The WHO classification suggests the criterion of a persistent increase (>2 × 109/l and >6 months) of circulating large granular lymphocytes without an identifiable cause for the diagnosis of these two disorders. However, cases that have fewer than 2 × 109/l circulating large granular lymphocytes but meet the other criteria (i.e. cytopenias, monoclonal circulating lymphocytes) are still consistent with these diagnoses [1]. The lymphocytes are very similar to normal large granular lymphocytes (Figure 19.2). In some patients there is neutropenia, anaemia with macrocytosis, anaemia with a low reticulocyte count (associated with red cell aplasia), anaemia with a high reticulocyte count (associated with autoimmune haemolytic anaemia) or thrombocytopenia. Some patients have hypergammaglobulinaemia and a positive rheumatoid factor; antinuclear antibodies and other autoantibodies may be present. Hypogammaglobulinaemia is much less common. The direct antiglobulin test may be positive.

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