Abstract
BackgroundEBV-associated T/NK-cell lymphoproliferative diseases (TNKLPD) is a rare spectrum of disease that occurs more commonly in Asia, and Central and South America. It commonly affects children and young adults and is an aggressive disease that is poorly understood with no known biologic markers that can predict prognosis. The systemic form of TNKLPD includes chronic active EBV infection of T/NK type, aggressive NK cell leukemia and systemic EBV + T-cell lymphoproliferative disease of childhood.MethodsIn this study, we analyse the clinicopathologic and genetic features of 22 cases of systemic TNKLPD in non-immunocompromised patients, including chronic active EBV infection of T/NK cell type and systemic EBV + T-cell lymphoproliferative disease of childhood. We also performed gene expression profiling in a subset of cases to identify markers that may be of prognostic relevance and validated our results using immunohistochemistry.ResultsThe median age is 14.9 years and two of our 22 cases occurring in patients older than 30 years. Fifteen of 17 cases (88%) with adequate data were of T-cell origin. Eleven of 22 cases revealed polymorphic cellular infiltrate (P-group) while the rest showed monomorphic lymphoid infiltrate (M-group). We found a significant difference in survival between P-group vs M-group patients with median survival not yet reached in P-group, and 1 month in M-group (p = 0.0001), suggesting a role for morphology in predicting patient outcome. We also performed gene expression profiling in a subset of patients and compared the genes differentially expressed between P-group and M-group cases to identify markers of prognostic value. We identified cyclin E2 gene and protein to be differentially expressed between patients with good outcome (P-group, median expression 8%) and poor outcome (M-group, median expression 42%) (p = 0.0005). In addition, the upregulation of cyclin E2 protein in M-group cases correlated with a higher Ki67 proliferation rate (Pearson correlation r = 0.73, p = 0.0006) detected by immunohistochemistry. High cyclin E2 expression was also significantly associated with shorter survival (p = 0.0002).ConclusionOur data suggests the potential role of monomorphic morphology, high cyclin E2 and Ki67 expression as adverse prognostic factors for TNKLPD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0165-x) contains supplementary material, which is available to authorized users.
Highlights
Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative diseases (TNKLPD) is a rare spectrum of disease that occurs more commonly in Asia, and Central and South America
Our data suggests the potential role of monomorphic morphology, high cyclin E2 and Ki67 expression as adverse prognostic factors for TNKLPD
TNKLPD is rare in the Western population and occurs with increased frequency in Asians, Native Americans from Central and South America and Mexico [1,2] Morphologically, it is characterized by a wideranging cytological appearance from reactive appearance to overt leukemia/lymphoma [5,6,7]
Summary
EBV-associated T/NK-cell lymphoproliferative diseases (TNKLPD) is a rare spectrum of disease that occurs more commonly in Asia, and Central and South America. The systemic form of TNKLPD includes chronic active EBV infection of T/NK type, aggressive NK cell leukemia and systemic EBV + T-cell lymphoproliferative disease of childhood. The systemic form of TNKLPD includes chronic active EBV infection of T/NK-cell type (CAEBV), aggressive NK cell leukemia (ANKL) and systemic EBV-positive Tcell lymphoproliferative disease of childhood (STLPDC) [1,2,3,4]. Recent efforts have been made to achieve international consensus on the nomenclature and classification of TNKLPD and it is recognized that most of the EBV-associated T/NK LPD in immunocompetent children and young adults with systemic presentation belong to the same spectrum of disease, including CAEBV and STLPDC. The systemic form includes CAEBV-T/NK, ANKL and STLPDC
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