Lymphoma & related disorders
Mature T/NK cell disorders
T/NK cell disorders with a leukemic component
NK large granular lymphocytic leukemia
Author: Dragos C. Luca, M.D.
Last author update: 1 January 2012
Last staff update: 26 November 2024 (update in progress)
Copyright: 2001-2024, PathologyOutlines.com, Inc.
PubMed search: Chronic lymphoproliferative disorders NK cells
Table of Contents
Definition / general | Terminology | Epidemiology | Etiology | Sites | Clinical features | Case reports | Treatment | Postulated normal counterpart | Microscopic (histologic) description | Positive stains | Negative stains | Flow cytometry images | Molecular / cytogenetics descriptionCite this page: Luca DC. NK large granular lymphocytic leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBchronicNK.html. Accessed December 17th, 2024.
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
- CD16, CD56 (usually weak), often cytoplasmic CD3ε, TIA1, granzyme B & M (Am J Pathol 2004;165:1117)
- May have diminished or lost expression of CD2, CD7 and CD57
- May see aberrant coexpression of CD5 and abnormal uniform expression of CD8
- Abnormal KIR expression (restricted KIR isoforms or complete lack of KIR), uniform bright CD94 / NKG2A, diminished CD161)
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
