Lymphoma & related disorders

Mature T/NK cell disorders

T/NK cell disorders with a leukemic component

Chronic lymphoproliferative disorders of NK cells

Last author update: 1 January 2012
Last staff update: 29 August 2022

Copyright: 2001-2023,, Inc.

PubMed search: Chronic lymphoproliferative disorders NK cells

Dragos C. Luca, M.D.
Page views in 2022: 1,477
Page views in 2023 to date: 1,036
Cite this page: Luca DC. Chronic lymphoproliferative disorders of NK cells. website. Accessed October 2nd, 2023.
Definition / general
  • Chronic lymphoproliferative disorders of NK cells (CLPD-NK, provisional entity) are characterized by a persistent (> 6 months) increase in peripheral blood NK cells (usually ≥ 2×109/L) without a clearly identified cause (WHO 2008)
  • Chronic NK cell lymphocytosis, chronic NK-LGL LPD, NK cell lineage granular lymphocyte proliferative disorder, NK cell LGL lymphocytosis, indolent large granular NK cell LPD
  • Rare and heterogeneous; difficult to distinguish between reactive and neoplastic without highly specialized techniques
  • Predominantly adults (median age 60 years)
  • No gender predominance, no racial or genetic predisposition
  • Autoimmune disorders or viral infections may be accompanied by a transient increase in circulating NK cells
  • Viral stimulus postulated as an activation factor leading to selection of NK cell clones (no evidence of direct NK cell infection observed so far)
  • May have genetic susceptibility related to haplotypes containing higher numbers of KIR
  • Predominantly peripheral blood and bone marrow
Clinical features
  • Most patients asymptomatic
  • May have systemic symptoms; variable cytopenias (mainly neutropenia and anemia)
  • Rarely lymphadenopathy, hepatosplenomegaly and skin lesions
  • Sometimes associated with solid tumors, hematologic neoplasms, vasculitis, splenectomy, neuropathy and autoimmune disorders
Case reports
  • 65 year old man with a preexisting, untreated indolent NK cell lymphoproliferative disorder evolving into an aggressive extranodal NK cell lymphoma (Am J Surg Pathol 2005;29:1540)
Treatment and prognosis:
  • Usually indolent clinical course over a prolonged period; occasional disease progression with increasing lymphocytosis and worsening cytopenias (Br J Haematol 1999;106:960)
  • Cytopenias, recurrent infections, comorbidity and cytogenetic abnormalities may indicate worse prognosis
  • Rare cases of spontaneous regression or transformation to an aggressive NK cell disorder
Postulated normal counterpart
  • Mature NK cell
Microscopic (histologic) description
  • Peripheral blood: NK cells of intermediate size with moderate amounts of slightly basophilic cytoplasm and coarse azurophilic granules, round nuclei, condensed chromatin
  • Bone marrow: intrasinusoidal and interstitial infiltration by cells with modest amounts of pale cytoplasm and small, minimally irregular nuclei; difficult to identify without immunostains
Positive stains
Negative stains
Flow cytometry images

Images hosted on other servers:

Characteristic immunophenotype

Immunophenotypic comparison

Molecular / cytogenetics description
  • Usually normal karyotype with no Ig or TCR gene rearrangements
  • May be able to use X chromosome inactivation to prove clonality in female patients
Back to top
Image 01 Image 02