Systemic Epstein-Barr virus-positive T-cell lymphoproliferative disease of childhood: Report of a case with review of the literature.

Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease (LPD) of childhood is an extremely rare and distinct clinicopathological entity. The majority of these cases occur with an apparent primary EBV infection. In this study, we describe a case of systemic EBV-positive T-cell LPD of childhood in a 23-year-old female with primary EBV infection, and review the clinicopathological features of this disease. A 23-year-old previously healthy female without an immunocompromized status presented with an acute onset of high fever. Laboratory examinations revealed a markedly elevated white blood cell count and liver and renal function. Peripheral blood smears identified a number of atypical lymphocytes with small azurophilic granules in the cytoplasm. Bone marrow aspiration revealed marked proliferation of small-sized lymphocytes with convoluted nuclei, which expressed EBER1, CD3, CD8 and cytotoxic granules. Monoclonal rearrangements of T-cell receptors were also detected. The patient underwent chemotherapy, but succumbed to multiorgan failure 20 weeks after administration. Upon review of 17 cases of this disease, including the one in the present study, we identified that the major clinicopathological features of systemic EBV-positive T-cell LPD of childhood are as follows: i) clonal systemic proliferation of EBV-infected T-cells that appear morphologically innocuous with an activated cytotoxic phenotype; ii) a high prevalence in the Asian population, commonly affecting children and young adults; iii) a predilection for males; iv) most commonly involved sites are the liver, spleen, lymph node and bone marrow, and the main clinical presentations are hepatosplenomegaly, fever and pancytopenia; v) almost all cases have an aggressive clinical course, which results in mortality. Cytological atypia of the neoplastic cells in this disease, as observed in the present case, is minimal. This study revealed that the cytomorphological features of atypical lymphocytes in the peripheral blood are indistinguishable from those of infectious mononucleosis.