Lymphoma & related disorders
Mature T/NK cell disorders
T/NK cell disorders with a leukemic component
Aggressive NK cell leukemia

Topic Completed: 1 August 2011

Minor changes: 11 January 2021

Copyright: 2001-2021,, Inc.

PubMed Search: aggressive NK cell leukemia

Dragos C. Luca, M.D.
Page views in 2020: 834
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Cite this page: Luca DC. Aggressive NK cell leukemia. website. Accessed January 22nd, 2021.
Definition / general
  • Asian young to middle age adults with fever, hepatosplenomegaly, lymphadenopathy
  • Rare, especially in non-Asian populations
  • Median age 42 year; either no sex predilection or slight male predominance
  • Most commonly peripheral blood, bone marrow, liver and spleen, but any organ can be affected
  • Overlap with extranodal NK/T cell lymphoma with multiorgan involvement may exist; unclear if they represent different facets of the same disease
  • Strong association with EBV
  • Some overlap with EBV+ T cell lymphoproliferative disorders of childhood may exist
Clinical features
  • Highly aggressive clinical course
  • Constitutional symptoms and leukemic blood picture including leukemic cells in variable number, and various cytopenias
  • Hepatosplenomegaly, sometimes lymphadenopathy
  • Possible complications: coagulopathy, hemophagocytic syndrome, multiorgan failure
  • Rare cases may evolve from extranodal NK/T cell lymphoma or chronic lymphoproliferative disorders of NK cells
Prognosis and treatment
  • Fulminant course in most cases
  • Median survival < 2 months
  • Poor response to chemotherapy, relapse almost always in patients with remission with or without BMT
Case reports
Postulated Normal Counterpart
  • NK cells
Microscopic (histologic) description
  • Peripheral blood demonstrates large cells with abundant blue cytoplasm, azurophilic granules, irregular nuclei, open chromatin, distinct nucleoli
  • Sometimes indistinguishable from normal large granular lymphocytes
  • Variable BM infiltration; destructive tissue infiltrates with generally monotonous nuclei but sometimes pleomorphic, apoptosis, necrosis, variable angioinvasion
Positive stains
Negative stains
Molecular / cytogenetics description
  • No T cell receptor gene rearrangement; EBV particles often present (> 90%)
  • del(6)(q21q25), 11q deletion
  • Leukemia vs. lymphoma: 7p-, 17p- and 1q+ more frequent in leukemia while 6q- more common in lymphoma
  • Array based comparative genomic hybridization analysis: clear genetic differences between aggressive NK cell leukemia and extranodal NK/T cell lymphoma, suggesting two distinct diseases
Differential diagnosis
  • Extranodal NK/T cell lymphoma: leukemic cases have younger median age by > 10 years, frequent hepatosplenic and bone marrow involvement, rare cutaneous involvement, uniformly fatal outcome irrespective of treatment, frequent CD16 expression
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