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Lymphoma - Non B cell neoplasms

T/NK cell disorders

Aggressive NK cell leukemia


Reviewer: Dragos Luca, M.D. (see Reviewers page)
Revised: 29 October 2011, last major update August 2011
Copyright: (c) 2001-2011, PathologyOutlines.com, Inc.

Definition
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● A systemic neoplastic proliferation of NK cells almost always associated with Epstein-Barr virus (EBV) and an aggressive clinical course (WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th Edition, Lyon 2008)

Epidemiology
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● Asian young to middle-aged adults with fever, hepatosplenomegaly, lymphadenopathy
● Rare, especially in non-Asian populations
● Median age 42 year; either no sex predilection or slight male predominance

Etiology
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● Strong association with EBV
● Some overlap with EBV+ T cell lymphoproliferative disorders of childhood may exist

Sites
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● 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

Clinical features
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● 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
Table: clinical features of 22 cases

Case reports
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● 11 month old girl (Arch Pathol Lab Med 2001;125:413)
● 28 year old woman with successful allogeneic stem cell transplantation (Intern Med 2010;49:1907)
● 44 year old woman with recalcitrant hemophagocytic syndrome (Eur J Haematol 2008;81;236)
● 48 year old man with prior EBV+ Hodgkin lymphoma (Pathol Res Pract 2009;205:730)
● Coexisting with acute monocytic leukemia and CMV infection (Int J Hematol 2008;87:553)
● Presenting with hemophagocytic syndrome (Pediatr Blood Cancer 2008;50:654)

Treatment and prognosis
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● Fulminant course in most cases
● Median survival <2 months
● Poor response to chemotherapy, relapse almost always in patients with remission with or without BMT
Table: therapy/Outcome of 22 cases

Postulated normal counterpart
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● NK cells

Micro description
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● 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

Micro images
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Left to right: lymph node, bone marrow, peripheral blood


CD56, CD43, CD45, TdT

Positive stains
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● CD2, CD3ε, CD16 (75%), CD56, TIA-1, variable CD8, may be positive with polyclonal CD3
● May express CD11b
● FAS ligand (including high serum levels)
Table: phenotypic analysis of 22 cases

Negative stains
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● CD3 (surface), CD4, CD57

Flow cytometry images
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Image

Genetics and Molecular
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● 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
Table: cytogenetics of 22 cases

Differential diagnosis
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● 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)
Table comparing Nasal NK cell lymphoma, non-nasal NK cell lymphoma and NK cell leukemia/lymphoma

Additional references
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● Review articles: Br J Haematol 2007;139:532, Leukemia 2005;19:2186, Leukemia 2004;18:763, Cancer 2008;112:1425

End of Lymphoma - Non B cell neoplasms > T/NK cell disorders > Aggressive NK cell leukemia


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