Aggressive NK-cell leukemia
Aggressive NK-cell leukemia
Classification & external resources
Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.
It is also called aggressive NK-cell lymphoma, or large granular lymphocyte leukemia, NK-cell type
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.
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.
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.
Leukemic cells are invariably present in samples of peripheral blood to a variable extent. Pancytopenia (anemia, neutropenia, thrombocytopenia) is commonly seen as well.
Sites 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.
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 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.
Leukemic involvement of organs is typically destructive on tissue sections with necrosis and possibly angioinvasion, and the monotonous infiltrate may be diffuse or patchy.
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.
|| CD2, CD3ε, CD56, perforin, granzyme B, TIA-1
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.
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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
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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
Kwong YL, Chan AC, Liang RH. "Natural killer cell lymphoma/leukemia: pathology and treatment." Hematol Oncol. 1997 May;15(2):71-9. PMID: 9375032
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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
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Oshimi K. "Lymphoproliferative disorders of natural killer cells." Int J Hematol. 1996 Jun;63(4):279-90. PMID: 8762811
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
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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
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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
|Hematological malignancy histology (ICD-O 9590-9989)|
|Lymphomas (9590-9759)||Hodgkin's lymphoma vs. Non-Hodgkin lymphoma - Diffuse lymphoma vs. Follicular lymphoma|
B-cell lymphoma (Small cell, Primary effusion, Diffuse large, ,Burkitt's, Splenic marginal zone, MALT)
mast cell tumor (Mast-cell sarcoma, Malignant mastocytosis, Malignant histiocytosis, Langerhans cell histiocytosis)
T-cell lymphoma (Cutaneous , Mycosis fungoides/Sézary's disease, Angioimmunoblastic, Anaplastic large cell, Hepatosplenic)
plasma cell (Plasmacytoma, Multiple myeloma)
|Immunoproliferative disorders (9760-9799)||Waldenström macroglobulinemia - Lymphomatoid granulomatosis|
|Lymphoid leukemias (9800-9839)||ALL - CLL - T-cell leukemia (Adult, Large granular lymphocyte, Prolymphocytic, Acute lymphoblastic) - B-cell leukemia (Prolymphocytic)|
|Myeloid leukemias (9840-9939, 9963)||AML (M2, APL/M3, AMoL/M5, Erythroleukemia/M6) - CML (CMoL, CNL, Philadelphia chromosome) - Granulocytic sarcoma|
|Other leukemias (9940-9949)||Hairy cell leukemia - Aggressive NK-cell leukemia|
|Myeloproliferative disease (9950-9961)||Polycythemia vera - Essential thrombocytosis - Myelofibrosis|
|Other (9964-9989)||Hypereosinophilic syndrome - Post-transplant lymphoproliferative disorder - Myelodysplastic syndrome|