Aggressive NK-cell leukemia

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eMedicineTopic = 776
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Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9192774&query_hl=4&itool=pubmed_ExternalLink] Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, Cheung MM, Lau WH. "Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm." Blood. 1997 Jun 15;89(12):4501-13. PMID 9192774] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2375924&query_hl=6&itool=pubmed_ExternalLink] Imamura N, Kusunoki Y, Kawa-Ha K, Yumura K, Hara J, Oda K, Abe K, Dohy H, Inada T, Kajihara H, "et al". "Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells." Br J Haematol. 1990 May;75(1):49-59. PMID 2375924] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10389582&query_hl=10&itool=pubmed_ExternalLink] Chan JK. "Natural killer cell neoplasms." Anat Pathol. 1998;3:77-145. PMID 10389582]

It is also called "aggressive NK-cell lymphoma", or "large granular lymphocyte leukemia, NK-cell type" [http://www.iarc.fr/WHO-BlueBooks/BBwebsite/bb3.html] Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds): World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. IARC Press: Lyon 2001 ]

Epidemiology

This rare form a leukemia is more common among Asians in comparison to other ethnic groups. It is typically diagnosed in adolescents and young adults, with a slight predominance in males. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=7817949&query_hl=18&itool=pubmed_ExternalLink] Kwong YL, Wong KF, Chan LC, Liang RH, Chan JK, Lin CK, Chan TK. "Large granular lymphocyte leukemia. A study of nine cases in a Chinese population." Am J Clin Pathol. 1995 Jan;103(1):76-81. PMID 7817949] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=9375032&query_hl=22&itool=pubmed_ExternalLink] Kwong YL, Chan AC, Liang RH. "Natural killer cell lymphoma/leukemia: pathology and treatment." Hematol Oncol. 1997 May;15(2):71-9. PMID 9375032] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8088773&query_hl=24&itool=pubmed_ExternalLink] Gelb AB, van de Rijn M, Regula DP Jr, Cornbleet JP, Kamel OW, Horoupian DS, Cleary ML, Warnke RA. "Epstein-Barr virus-associated natural killer-large granular lymphocyte leukemia." Hum Pathol. 1994 Sep;25(9):953-60. PMID 8088773] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8762811&query_hl=26&itool=pubmed_ExternalLink] Oshimi K. "Lymphoproliferative disorders of natural killer cells." Int J Hematol. 1996 Jun;63(4):279-90. PMID 8762811]

Clinical features

Etiology

This disease has a strong association with the Epstein-Barr virus (EBV), but the true pathogenesis of this disease has yet to be described. The cell of origin is believed to be an NK cell. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Presentation

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=8854571&query_hl=29&itool=pubmed_ExternalLink] Kobayashi Y, Uehara S, Inamori K, Shirato R, Ozawa K, Sklar J, Asano S. "Hemophagocytosis as a para-neoplastic syndrome in NK cell leukemia." Int J Hematol. 1996 Aug;64(2):135-42. PMID 8854571] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1746541&query_hl=31&itool=pubmed_ExternalLink] Okuda T, Sakamoto S, Deguchi T, Misawa S, Kashima K, Yoshihara T, Ikushima S, Hibi S, Imashuku S. "Hemophagocytic syndrome associated with aggressive natural killer cell leukemia." Am J Hematol. 1991 Dec;38(4):321-3. PMID 1746541]

Laboratory findings

Leukemic cells are invariably present in samples of peripheral blood to a variable extent. Pancytopenia (anemia, neutropenia, thrombocytopenia) is commonly seen as well.

ites of involvement

This disease is typically found and diagnosed in peripheral blood, and while it can involve any organ, it is usually found in the spleen, liver, and bone marrow.

Morphology

Peripheral blood

The leukemic cells have a diameter mildly greater than a large granular lymphocyte (LGL) and have azurophilic granules and nucleoli of varying prominence. Nuclei may be irregular and hyperchromatic.

Bone marrow

Bone marrow involvement runs the spectrum between an inconspicuous infiltrate to extensive marrow replacement by leukemic cells. Reactive histiocytes displaying hemophagocytosis can been seen interspersed in the neoplastic infiltrate.

Other organs

Leukemic involvement of organs is typically destructive on tissue sections with necrosis and possibly angioinvasion, and the monotonous infiltrate may be diffuse or patchy.

Molecular findings

Immunophenotype

The immunophenotype of this disease is the same as extranodal NK/T-cell lymphoma, nasal type and is shown in the table below. CD11b and CD16 show variable expression.

Genetic findings

Due to the myeloid lineage, clonal rearrangements of lymphoid (T cell receptor; B cell receptor) genes are not seen. The genome of the Epstein Barr virus (EBV) is detected in many cases, along with a variety of chromosomal abnormalities. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=10439361&query_hl=38&itool=pubmed_ExternalLink] Wong KF, Zhang YM, Chan JK. "Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia--is there a consistent pattern?" Leuk Lymphoma. 1999 Jul;34(3-4):241-50. PMID 10439361]

References