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

Abstract

Aggressive natural killer (NK) cell leukemia (ANKL) is a prototype of an Epstein-Barr virus (EBV)-associated lymphoid malignancy, which is characterized by a fulminant clinical course and a median survival interval <2 months. EBV negativity in ANKL is uncommon, and the characteristics of EBV-negative ANKL are not well defined. We compared the clinicopathological characteristics of EBV-negative ANKL patients (group 1, n = 2) with those of EBV-positive ANKL patients (group 2, n = 14) and reviewed the literature for reports on EBV-negative ANKL cases. EBV-negative and EBV-positive ANKL patients had similar clinical and pathological characteristics, but EBV-negative patients had a longer survival than EBV-positive patients (11.5 vs. 1.5 months, respectively). EBV-negative patients achieved complete remission, but tumors often relapsed after a short interval. In conclusion, EBV-negative ANKL is an uncommon malignancy that pursues a less aggressive clinical course than EBV-positive ANKL.

Natural killer cell neoplasm: biology and pathology

“…EBER in situ hybridization highlights neoplastic cells (e) episomal form in most cases of ANKL. EBV-negative ANKL has been reported in up to 10% of cases [34,35,37] and its histological and clinical features are similar to those of EBV-positive ANKL except for a few cases in which the clinical course was less aggressive [35]. Because EBV is the most important factor that defines the pathogenesis and clinical features of ANKL, an extensive immunophenotypic study should be conducted to confirm diagnosis.…”

“…Defective T-cell and NK-cell responses to EBV infection may play a role in the development of this lymphoproliferative disease. The age distribution of ANKL patients has two peaks, one at the 20th and one at the 40th year [34][35][36][37]. The median age is around 40 years.…”

“…Hematophagocytosis, dyserythropoiesis, and stromal degeneration are the most frequent findings [34]. The bone marrow also shows massive focal or subtle infiltration with neoplastic cells which have a broad spectrum of morphologies, ranging from small to medium-sized lymphocytes without significant atypia to pleomorphic large tumor cells [35,38] (Fig. 2).…”

“…A cytogenetic study showed that there is often a complex karyotype and loss of chromosome 6q [35]. A recent array-based comparative genomic hybridization study showed recurrent gain of 1q and loss of 7p15.1-p22.3 and 17p13.1 in ANKL.…”

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

“…ANKL patients often present with high fever, poor performance status, pancytopenia, hepatosplenomegaly, coagulopathy, multiple organ failure, and haemophagocytic syndrome [2,8]. The disease shows a highly aggressive clinical phenotype: most patients die within 2 months from diagnosis [2,10,11]. Up to now, there is no standardized therapeutic regimen to effectively control the progression of this disease, thus leading to a very poor clinical prognosis.…”