[Clinicopathologic features of systemic EBV-positive T/NK-cell lymphoproliferative disease in adults]

Zhonghua Bing Li Xue Za Zhi. 2011 Apr;40(4):227-34.
[Article in Chinese]

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.

MeSH terms

  • Adult
  • Aged
  • CD3 Complex / metabolism
  • Epstein-Barr Virus Infections / pathology*
  • Female
  • Follow-Up Studies
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor
  • Granzymes / metabolism
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Killer Cells, Natural / pathology*
  • Lymphoproliferative Disorders / drug therapy
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / metabolism
  • Lymphoproliferative Disorders / pathology*
  • Lymphoproliferative Disorders / virology
  • Male
  • Middle Aged
  • Poly(A)-Binding Proteins / metabolism
  • RNA, Viral / metabolism
  • Retrospective Studies
  • Survival Rate
  • T-Cell Intracellular Antigen-1
  • T-Lymphocytes / pathology*
  • Young Adult

Substances

  • CD3 Complex
  • Epstein-Barr virus encoded RNA 1
  • Poly(A)-Binding Proteins
  • RNA, Viral
  • T-Cell Intracellular Antigen-1
  • TIA1 protein, human
  • Granzymes