Lymphoma & related disorders
Mature T/NK cell disorders
T/NK cell disorders with a leukemic component
Aggressive NK cell leukemia
Author: Dragos C. Luca, M.D.
Topic Completed: 1 August 2011
Minor changes: 11 January 2021
Copyright: 2001-2021, PathologyOutlines.com, Inc.
PubMed Search: aggressive NK cell leukemia
Table of Contents
Definition / general | Epidemiology | Sites | Etiology | Clinical features | Prognosis and treatment | Case reports | Postulated Normal Counterpart | Microscopic (histologic) description | Positive stains | Negative stains | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Luca DC. Aggressive NK cell leukemia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomanonBNKcell.html. Accessed January 22nd, 2021.
Definition / general
- 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 Tissue, 4th ed, 2008
Epidemiology
- Asian young to middle age adults with fever, hepatosplenomegaly, lymphadenopathy
- Rare, especially in non-Asian populations
- Median age 42 year; either no sex predilection or slight male predominance
Sites
- 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
Etiology
- Strong association with EBV
- Some overlap with EBV+ T cell lymphoproliferative disorders of childhood may exist
Clinical features
- 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
Prognosis and treatment
- Fulminant course in most cases
- Median survival < 2 months
- Poor response to chemotherapy, relapse almost always in patients with remission with or without BMT
Case reports
- 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)
Postulated Normal Counterpart
- NK cells
Microscopic (histologic) description
- 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
Positive stains
Molecular / cytogenetics description
- 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
Differential diagnosis
- 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
Additional references
- Review articles: Br J Haematol 2007;139:532, Leukemia 2005;19:2186, Leukemia 2004;18:763, Cancer 2008;112:1425
