Aggressive NK-cell leukaemia is a disease derived from activated natural killer (NK) cells. It is frequently associated with the Epstein–Barr virus (EBV) and has an aggressive clinical course . It is more common in Far East Asia than in the West. In a few cases, the disease evolves from a chronic lymphoproliferative disorder of NK cells or from extranodal T/NK cell lymphoma. It is uncertain whether aggressive NK-cell leukaemia represents the leukaemic counterpart of extranodal T/NK cell lymphoma.
Patients generally present with constitutional symptoms, cytopenias, a leukaemic picture and often organomegaly and abnormal coagulation. The disease course may be complicated by a haemophagocytic syndrome and multiorgan failure.
Haematological and pathological features
The number of circulating neoplastic cells may be low or high. The cells can either resemble normal large granular lymphocytes, being similar to the neoplastic cells of T-lineage large granular lymphocytic leukaemia (T-LGLL) or can be more atypical (Figures 20.1, 20.2, 20.3, 20.4); in the latter cases they may be increased in size and have moderately basophilic cytoplasm or have irregular or hyperchromatic nuclei. Anaemia, neutropenia and thrombocytopenia are common. The bone marrow shows infiltration by neoplastic cells with a variable pattern of involvement ranging from subtle to diffuse (Figure 20.5). There is often haemophagocytosis. The involvement of EBV can be demonstrated by in situ hybridization (Figure 20.6). Other tissues involved are usually diffusely infiltrated by neoplastic cells; necrosis and apoptosis are common.
Peripheral blood film from a patient with aggressive NK-cell leukaemia showing atypical large granular lymphocytes, many of which are larger than their normal equivalent and have lobulated nuclei. Romanowsky stain, ×100 objective.
Neoplastic cell from a patient with aggressive NK-cell leukaemia showing some chromatin condensation and large prominent azurophilic granules. Romanowsky stain, ×100 objective (detail).
Ultrastructure of a neoplastic cell from a patient with aggressive NK-cell leukaemia showing cytoplasmic granules and a somewhat irregular nucleus with a nucleolus. Lead nitrate and uranyl acetate stain.
Bone marrow film from a patient with aggressive NK-cell leukaemia showing pleomorphic large granular lymphocytes, with irregular nuclei with nucleoli. Romanowsky stain, ×100 objective.
Bone marrow section from a patient with aggressive NK-cell leukaemia showing infiltration by neoplastic cells highlighted with CD2 and CD56 staining: A haematoxylin and eosin (H&E) stain, ×40 objective; B immunoperoxidase for CD2, ×20 objective; C immunoperoxidase for CD56, ×20 objective.