EBV-Associated T/NK-Cell Lymphoproliferative Disorders in Children and Adolescents: A Clinicopathologic and Molecular Study of 10 Cases
S Wang, SEC Quek, B Mow, WJ Chng, A Yeoh, TC Quah, PL Tan, SB Ng. National University Hospital, Singapore, Singapore; King's College, London, United Kingdom
Background: Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (EBV-T/NK-LPD) in children and adolescents is a collective term referring to a heterogeneous group of entities characterized by a proliferation of EBV-associated cytotoxic T/NK-cells. The perplexity in nomenclature and diagnosis of EBV-T/NK-LPD stems from the lack of well-defined diagnostic criteria and overlapping clinicopathologic features. A classification system for EBV-T/NK-LPD was recently proposed by the CAEBV Study Group. This study describes the genetic and clinicopathologic features of 10 cases of pediatric EBV-T/NK-LPD and assesses the predictive value of the novel classification system.
Design: Immunohistochemistry for CD3, CD20, CD4, CD8, CD56, granzyme B and TIA1, EBER in-situ hybridization and TCR-gene clonality assay were performed. Cases were classified as follows: category A1, polymorphic LPD without clonal proliferation of EBV-infected cells; category A2, polymorphic LPD with clonal proliferation of EBV-infected cells; category A3, monomorphic LPD with clonal proliferation of EBV-infected cells; category B, monomorphic LPD with clonal proliferation of EBV-infected cells and fulminant course.
Results: Patients included 3 females and 7 males with a median age of 13 years (range, 16 months to 21 years). The clinical presentation included fever, hepatosplenomegaly, pancytopenia, liver dysfunction, skin rash and lymphadenopathy. Six cases had monomorphic LPD, and four showed polymorphic LPD. All cases had an EBV-associated cytotoxic T/NK-cell infiltrate with the following CD8/CD4 profile: CD8+/CD4- (7/10), CD8-/CD4+ (1/10), CD8-/CD4- (2/10). Clonal TCR gene rearrangements were detected in 6 of 9 patients. All patients in categories B (5 cases) and A3 (1 case) died within 2 months of diagnosis. One patient in category A2 survived for 3 years. Patients in categories A1 (1 case) and A2 (2 cases) remain alive (range, 4 to 40 months after diagnosis).
Conclusions: EBV-T/NK-LPD in children and adolescents is a distinctive entity associated with aggressive behavior and high mortality. Categorization based on morphology, clonality and clinical presentation, according to the novel CAEBV Study Group classification, appears to be useful in predicting clinical outcome.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 189, Wednesday Morning