Lymphoma and plasma cell neoplasms
T / NK cell disorders
Chronic lymphoproliferative disorders of NK cells

Author: Dragos Luca, M.D. (see Authors page)

Revised: 24 March 2017, last major update January 2012

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PubMed search: chronic lymphoproliferative [title] disorders NK cells

Cite this page: Chronic lymphoproliferative disorders of NK cells. PathologyOutlines.com website. http://pathologyoutlines.com/topic/lymphomanonBchronicNK.html. Accessed May 24th, 2017.
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)
Terminology
  • 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
Epidemiology
  • 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
Etiology
  • 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
Sites
  • 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
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