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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Chronic lymphoproliferative disorders of NK cells


Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 8 January 2012, last major update January 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

General
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● Chronic lymphoproliferative disorders of NK cells (CLPD-NK, provisional entity) are characterized by a persistent (>6 months) increase in peripheral blood NK cells (usually ≥ 2x109/L) without a clearly identified cause (WHO 2008)

Terminology
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● 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
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● 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
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● 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
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● Predominantly peripheral blood and bone marrow

Clinical features
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● 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
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● Evolving into an aggressive extranodal NK-cell lymphoma (Am J Surg Pathol 2005;29:1540)

Treatment and prognosis
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● 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
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● Mature NK cell

Micro description
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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

Micro images
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Chronic lymphoproliferative disorder of NK cells

Positive stains
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● 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)

Negative stains
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● Surface CD3, EBV

Flow cytometry images
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Characteristic immunophenotype

   

Immunophenotypic comparison

Genetics & molecular
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● Usually normal karyotype with no Ig or TCR gene rearrangements
● May be able to use X-chromosome inactivation to prove clonality in female patients

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Chronic lymphoproliferative disorders of NK cells


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