Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection : a distinct clinicopathologic syndrome

• Published in: Blood 2000-07, Vol.96 (2), p.443-451
• Main Authors: QUINTANILLA-MARTINEZ, L, KUMAR, S, FEND, F, REYES, E, TERUYA-FELDSTEIN, J, KINGMA, D. W, SORBARA, L, RAFFELD, M, STRAUS, S. E, JAFFE, E. S
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biological and medical sciences; Child, Preschool; Epstein-Barr Virus Infections; Fatal Outcome; Female; Gene Rearrangement, B-Lymphocyte, Heavy Chain; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - classification; Herpesvirus 4, Human - genetics; Human viral diseases; Humans; Immunoglobulin Heavy Chains - genetics; Immunophenotyping; In Situ Hybridization; Infectious diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Liver - pathology; Lymphoproliferative Disorders - immunology; Lymphoproliferative Disorders - pathology; Lymphoproliferative Disorders - virology; Male; Medical sciences; RNA, Viral - analysis; RNA, Viral - genetics; Spleen - pathology; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v96.2.443

This study describes the clinicopathologic features of 5 patients who developed a fulminant Epstein-Barr virus (EBV)-positive clonal T-cell lymphoproliferative disorder (LPD) after acute EBV infection. One additional patient developed a similar disorder in the setting of long-standing chronic active EBV infection. Detailed immunophenotyping, in situ hybridization for EBV early RNA-1 (EBER1) and polymerase chain reaction (PCR) analyses for immunoglobulin (Ig) heavy chain and T-cell receptor (TCR)-gamma gene rearrangements were performed on paraffin-embedded tissue from all patients. In addition, EBV strain typing and detection of the characteristic 30-bp deletion of the latent membrane protein-1 (LMP-1) gene were performed by PCR. Controls included 8 cases of uncomplicated infectious mononucleosis (IM). Patients included 4 males and 2 females with a median age of 18 years (2-37 years). Three patients were Mexican, 2 were white, and 1 was of Asian descent. All presented with fever, hepatosplenomegaly, and pancytopenia; 5 were previously healthy, but had a clinical history of a recent viral-like upper respiratory illness (1 week to 2 months), and 1 patient had documented chronic active EBV infection for 7 years. Serologic data for EBV were incomplete but titers were either negative or only modestly elevated in 3 cases. In 1 case serology was consistent with severe chronic active EBV infection. In the remaining 2 cases serologic studies were not performed. All patients died within 7 days to 8 months of presentation with T-cell LPD. On histologic examination, the liver and spleen showed prominent sinusoidal and portal lymphoid infiltrates of CD3(+), beta F1(+), EBER1(+) T cells lacking significant cytologic atypia. Two cases were CD4(+), 2 cases were CD8(+), and 2 cases had admixed CD4(+) and CD8(+) cells without clear subset predominance. All were TIA-1(+), CD56(-). Only rare B cells were noted. Marked erythrophagocytosis was present. Molecular analysis revealed identical T-cell clones in 2 or more sites (liver, spleen, lymph node) in 5 cases. All patients carried type A EBV; 4 cases had wild-type EBV-LMP, and 2 showed the 30-bp deletion. This fulminant T-cell LPD after acute/chronic EBV infection is characterized by hepatosplenomegaly, often without significant lymphadenopathy, fever, liver failure, pancytopenia, and erythrophagocytosis indicative of a hemophagocytic syndrome. EBV serology may be misleading, with lack of elevated titers. The presence of an EB