Clinicopathologic features of systemic EBV-positive T-cell lymphoproliferative disease of childhood

Abstract

To study the clinicopathologic features, diagnosis and differential diagnosis of systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disease of childhood (CSEBV(+)T-LPD). Thirty cases of CSEBV(+)T-LPD were retrospectively studied by light microscopy, immunohistochemistry and in-situ hybridization for EBV-encoded RNA (EBER). The clinical information and follow-up data were analyzed. Nineteen of the 30 patients were males and 11 females. The median age of disease onset was 9 years (range = 1.5 to 32 years). The average duration between disease onset and diagnosis was 14 months. The major clinical manifestations were fever (96.7%), lymphadenopathy (83.3%) and hepatosplenomegaly (66.7%). Cutaneous manifestations were not uncommon, which included hypersensitivity to mosquito bite (13.3%) and skin rash (20.0%). Six of the 20 patients died on follow up. Histologically, the lymph nodes showed expansion of T zone, with diminished or effaced lymphoid follicles. The lymphoid cells were of small to medium size. Scattered large lymphoid cells were also identified in the expanded T zone. Furthermore, the liver and spleen showed mild to marked sinusoidal infiltration. In some cases, various degrees of sinus histiocytosis with erythrophagocytosis were present. Skin biopsies showed mild to marked degree of lymphocytes infiltration in dermis. Immunohistochemical study and in-situ hybridization showed that the EBER-positive cells were of T lineage and CD3 positive. They also expressed cytotoxic molecules granzyme B and TIA-1. Seven of the 8 cases examined were CD8 positive, while the remaining case was mainly CD4 positive. Thirteen of 15 cases were shown to be CD56 negative. The number of EBER-positive cells ranged from 5 to more than 500 per high-power field. These cells included small to large lymphoid cells located mostly in the expanded T zone and sometimes in the germinal centers. Nine of the 30 cases, which consisted mainly of medium to large-sized lymphoid cells, were also EBER positive. Systemic EBV-positive T-cell lymphoproliferative disease of childhood occurs most often in children and young adults, with a median age of 9 years. It has a subacute or chronic clinical course. Most of the patients have evidence of systemic disease, often with lymph node, liver, spleen and skin involvement. It carries a poor clinical outcome and can be life-threatening. The disease is characterized by a clonal proliferation of EBV-infected T cells with cytotoxic immunophenotype. Definitive diagnosis requires correlation between clinical, pathologic and ancillary investigation findings.