ABSTRACT
BACKGROUND: Aggressive natural killer-cell leukemia (ANKL) is a rare neoplasm characterized by systemic proliferation of NK cells. However, the differential diagnosis of NK lymphoproliferative disorders is difficult because of the absence of a distinct diagnostic hallmark. Therefore, to identify diagnostic markers for ANKL, we analyzed the clinical data and laboratory findings obtained for 20 patients with ANKL. METHODS: From January 2000 to July 2007, 20 patients were diagnosed with ANKL on the basis of bone marrow studies. We retrospectively analyzed the clinical features and laboratory findings, including the complete blood count, Epstein-Barr virus status, immunophenotype, and the cytogenetic results. RESULTS: The subjects included 6 women and 14 men (median age, 44 yr; range, 2-70 yr). Cytogenetic studies were performed in 18 patients, and karyotypic abnormalities were observed in 9 patients (50%). None of the cytogenetic abnormalities were constantly observed in all the patients. However, 6q abnormalities were observed in 4 patients (4/18, 22%). The immunophenotype of the leukemic NK-cells was cytoplasmic CD3+, surface CD3-, CD16/56+, CD2+, and CD5-. Notably, the CD7 antigen was absent in 10 patients (50%). When the CD7 loss was combined with cytogenetic abnormalities, clonal markers could be identified in 75% of the ANKL cases. CONCLUSIONS: The CD7 antigen loss was frequently observed in our series of ANKL patients. In conjunction with the cytogenetic findings, this characteristic immunophenotypic finding can serve as a reliable marker for the timely diagnosis of ANKL. Therefore, immunophenotypic analysis of CD7 expression should be included in the diagnosis of NK cell neoplasms.
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Antigens, CD7/analysis , Blood Cell Count , Cytogenetics , Herpesvirus 4, Human/isolation & purification , Immunophenotyping , Karyotyping , Leukemia, Large Granular Lymphocytic/diagnosis , Retrospective Studies , Biomarkers, Tumor/analysisABSTRACT
Epstein-Barr virus (EBV) infection is associated with various lymphoproliferative diseases, including Hodgkin lymphoma, extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma and post-transplant lymphoproliferative disorder. In the recent studies, the plasma EBV-DNA levels in patients with EBV-associated lymphoproliferative disease appeared to be correlated with the therapeutic response. Aggressive NK cell leukemia (ANKL) is a fatal disease that's characterized by high fever, lymphadenopathy, hepatosplenomegaly and frequent hemophagocytosis. No serological tumor marker for this malignancy has yet been identified for monitoring the disease and predicting the outcome. We experienced a case of aggressive natural killer cell leukemia in a 48-year-old man, and we serially monitored the plasma EBV DNA load by performing real time quantitative PCR assay. Serial measurements of the plasma EBV DNA level during therapy showed a close correlation between the clinical response and the changes in the plasma EBV DNA titers.