title: [Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults].
abstract: OBJECTIVE
  To study the clinicopathologic features, immunophenotype, clonality and Epstein-Barr virus (EBV) status of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults (ASEBV(+)T/NK-LPD).
  
  
  METHODS
  Twenty cases of ASEBV(+)T/NK-LPD were analyzed retrospectively with histopathologic review, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The follow-up data were collected.
  
  
  RESULTS
  There were altogether 15 males and 5 females. The median age of the patients was 34 years. The average duration from onset of symptoms to diagnosis was 8.7 months. Fever (18/20), hepatosplenomegaly (18/20) and lymphadenopathy (17/20) were the main clinical manifestations. Eleven of the 17 patients died during follow-up, with a mean survival of 2.9 months. Histologically, there was obvious expansion of T zone of the involved lymph nodes, associated with diminished lymphoid follicles. The interfollicular areas were widened and infiltrated by small to median-sized lymphoid cells which showed only mild atypia. Scattered large lymphoid cells were not uncommon. The nodal capsule was thickened in 6 cases. Focal necrosis was seen in 9 cases. Sinus histiocytic proliferation with erythrophagocytosis was observed in 3 cases. In addition, there were mild atypical lymphoid cells infiltrate into the liver, spleen, intestinal mucosa and bone marrow. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T-cell lineage, with CD3 expression. They were also positive for cytotoxic molecules (granzyme B or TIA-1). Only 1 case was CD56 positive. A predominance of CD8-positive cells was demonstrated in 8 of the 14 cases studied, while CD4-positive cells predominated in the remaining 5 cases. One case showed similar proportion of CD8 and CD4-positive cells. The number of EBER-positive cells ranged from 30 to more than 300 per high-power fields. These EBER-positive cells were of small to large size and located mainly in the expanded T zone and occasionally in the germinal centers. Three of the 7 cases exhibited clonal rearrangement of T-cell receptor gamma gene, while the other 4 cases exhibited polyclonal rearrangement of T-cell receptor gamma gene.
  
  
  CONCLUSIONS
  ASEBV(+)T/NK-LPD is a systemic disease with a subacute or chronic clinical course. Most patients suffer from relapsing fever, lymphadenopathy and hepatosplenomegaly. The disease is characterized by proliferation of EBV-infected cytotoxic T cells. The T zone of the involved lymph nodes shows expansion by mildly atypical lymphoid cells. The disease is associated with poor clinical outcome and can be life-threatening. The patients often die of multiorgan failure and bleeding.
authors: Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
authors: Xiao-Dan
authors: XD
authors: Zheng
authors: Xiao-Ge
authors: XG
authors: Zhou
authors: Yan
authors: Y
authors: Jin
authors: Jian-Lan
authors: JL
authors: Xie
authors: Xue-Jing
authors: XJ
authors: Wei
authors: Shu-Yuan
authors: SY
authors: Chen
authors: Xue
authors: X
authors: Mei
authors: Li-Ping
authors: LP
authors: Gong
authors: Bei-Bei
authors: BB
authors: Lü