Clinicopathological Features And Prognosis Of 21 Children With Epstein-barr Virus Positive T And NK-cell Lymphoproliferative Diseases

Objective:To analysis the clinicopathological characteristics and prognosis of children with Epstein-Barr virus positive T and NK-cell lymphoproliferative diseases.Methods:The current study retrospectively reviewed the clinical courses and outcomes of 21 children with a diagnosis of Epstein-Barr virus positive T and NK-cell lymphoproliferative diseases.And divided them into 3 groups according to clinicopathological features.Kaplan-Meier method and Cox proportional hazard model were performed to clarify prognostic factors.Results:Of these 21 patients,males were 12(57.1%),females were 9(42.9%).The median onset of age was 8 years(2-14 years),and the median clinical courses was 24.5 months(0.3-161 months).And they were clinically categorized into 3 groups:9 of CAEBV,8 of HV-LPD,and 4 of CSEBV+TCL.The major manifestations were fever(17/21,80.9%),hepatomegaly(15/21,71.4%),splenomegaly(14/21,66.7%),superficial lymphadenopathy(11,52.4%)and rash(10,47.6%).Laboratory examination showed that pancytopenia(10/11,47.6%),thrombocytopenia(11/21,52.4%),elevated alanine aminotransferase(9/21,42.9%),bilirubin metabolism disorder(7/21,33.3%),elevated lactate dehydrogenase(LDH)(11/21,52.4%).Secondary coagulation dysfunction,HLH,and renal dysfunction were present at rates of 33.3%,33.3%,and 14.3%,respectively.19 patients had EBV serological data with significant elevated EBV loads,more than 10~4copies/ml.In addition,VCA-Ig M were all negative and VCA-Ig G were all positive for 18 patients.All patients had detailed histopathological data,such as skin,lymph nodes and bone marrow specimen.Histopathological features were abnormal EBV positive lymphocytes infiltration into tissues.Some lymphocytes may show mild atypia.2 of CSEBV+TCL showed atypical tumor cell proliferation on biopsy.The immunohistochemical characteristics were CD3(+),CD7(+)and TIA-1(+),and partial combine with CD56(+).EBER positive cells were seen in all cases except for a partial bone marrow biopsy.The positive rate of TCR gene rearrangement studies was 55.6%(5/9).In a median follow-up period of 7months(0.3 to 59 months),and 16 patients(80%)died,one patient was lost to follow-up.Univariate analysis showed that fever(P=0.028),lymphadenopathy(P=0.037),thrombocytopenia(P=0.013),elevated LDH(P=0.003),elevated bilirubin(P=0),renal dysfunction(P=0.02),coagulation dysfunction(P=0),and the presence of HLH(P=0)were associated with poor prognosis.Multivariate analysis suggested that thrombocytopenia and elevated LDH were risk factors for mortality.Conclusion:1.The major manifestations of children with EBV-T/NK-LPDs are fever,hepatosplenomegaly,lymphadenopathy,and vaccina-like rash.When systemic damage occurs,it mainly involves the blood system and liver function.2.Histopathological features are EBV positive lymphocytes infiltrated into tissues.Immunohistochemical results showed that CD3,CD7,TIA-1 were positive,and some of them could be combined with CD56.EBBR was generally positive.3.EBV-T/NK-LPDs of children is rare.and when it occurs with systemic symptoms,it has rapid progression and high mortality.Thrombocytopenia and elevated LDH are independent factors for poor prognosis.4.The outcome of treatment regimens for patients with systemic symptomsusingantiviral therapy,glucocorticoid therapy alone or HLH treatment regimens,is unsatisfactory.