Aggressive Natural Killer Cell Leukemia: Report of a Chinese Series and Review of the Literature

Abstract

Aggressive natural killer cell leukemia (ANKL) is a rare Epstein-Barr virus (EBV)-associated fulminating disease that is widely disseminated at diagnosis. Because of its typically extranodal presentation, differing degrees of NK cell involvement, and varying bone marrow pathology, ANKL can be confused with a reactive process. These features, coupled with a rapidly fatal course, have hampered systematic study of the pathogenesis of ANKL. Nine cases of ANKL were diagnosed and characterized by a single laboratory over a 2-year period. Constant features at presentation included disseminated disease, high fever, bone marrow involvement, and a high lactate dehydrogenase index. All cases were positive for EBV early region protein and negative for latent membrane protein 1, and all had a germline T-cell receptor gene configuration. Peripheral blood counts were variable, with severe thrombocytopenia being the most frequently encountered abnormality (7 of 9 cases). Hematophagocytosis, dyserythropoiesis, and stromal degeneration were the most frequent findings in the bone marrow. Neoplastic cells in the bone marrow were consistently CD2+, CD56+, CD45+, CD34-, CD117-, CD4-, and surface CD3-. Most cases were HLA-DR+ (8/9) and CD8- (8/9). Complex clonal cytogenetic abnormalities were found in 8 of 9 cases. Because of its aggressive course, rapid and accurate diagnosis of ANKL is essential for a better understanding of the etiology, pathogenesis, and treatment of the disease.

Aggressive Natural Killer Cell Leukemia: Is Epstein-Barr Virus Negativity an Indicator of a Favorable Prognosis?

“…Four cases were identified using a PubMed search from 1968 to 2008 with the following key words: natural killer cell, natural killer cell leukemia, large granular lymphocyte leukemia and natural killer cell lymphoma [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. Cases with a history of chronic NK lymphocytosis were excluded.…”

Aggressive Natural Killer Cell Leukemia Secondary to Hodgkin Lymphoma: a Case Report and Review of the Literature

“…Aggressive Natural Killer Cell Leukemia (ANKL) is a rare disease, characterized by a clonal proliferation of neoplastic Natural Killer (NK) cells and a highly malignant clinical progression [1][2][3][4][5][6][7][8]. The diagnosis of ANKL is made usually by combining clinical presentations with the morphologic and immune-phenotypic features of neoplastic NK cells [1,7,9].…”

“…The diagnosis of ANKL is made usually by combining clinical presentations with the morphologic and immune-phenotypic features of neoplastic NK cells [1,7,9]. ANKL patients often present with high fever, poor performance status, pancytopenia, hepatosplenomegaly, coagulopathy, multiple organ failure, and haemophagocytic syndrome [2,8].…”

Aggressive Mature Natural Killer Cell Neoplasms: from Disease Biology to Disease Manifestations

“…Aggressive NK-cell leukemia is very rare and has a fulminant clinical course [2,[28][29][30][31][32]. Patients often present with systemic symptoms, BM involvement, pancytopenia, hepatosplenomegaly and abnormal liver function, and frequently develop HS, multiorgan failure and disseminated intravascular coagulation [33][34][35][36][37][38][39].…”