Clinical spectrum of lymphoproliferative disorders in renal transplant recipients and evidence for the role of Epstein-Barr virus

• Published in: Cancer research (Chicago, Ill.) Vol. 41; no. 11 Pt 1; pp. 4253 - 4261
• Main Authors: Hanto, D W, Frizzera, G, Purtilo, D T, Sakamoto, K, Sullivan, J L, Saemundsen, A K, Klein, G, Simmons, R L, Najarian, J S
• Format: Journal Article
• Language: English
• Published: United States 01-11-1981
• Subjects: Adolescent; Adult; Aged; Animals; Antibodies, Viral - analysis; B-Lymphocytes; Capsid - immunology; Epstein-Barr virus; Genes, Viral; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - immunology; Humans; Immunoglobulin G - analysis; Immunoglobulin M - analysis; Kidney Transplantation; Liver - microbiology; Lymph Nodes - microbiology; Lymphoproliferative Disorders - etiology; Lymphoproliferative Disorders - immunology; Lymphoproliferative Disorders - pathology; Middle Aged; Pharynx - microbiology; Tumor Virus Infections - immunology
• ISSN: 0008-5472

Six renal transplant recipients with abnormal lymphoproliferative disorders were studied in an attempt to define their clinical features and the role of Epstein-Barr virus (EBV) in their pathogenesis. Patients were either teenage (three) or in the sixth decade (three). The younger patients presented an average of 3 months after transplantation with fever, sore throat, and lymphadenopathy; had been markedly immunosuppressed; frequently had preceding or concomitant cytomegalovirus infections; and two of three had a rapidly fatal course. The older patients presented an average of 5 years after transplantation while on maintenance immunosuppressive drugs; in two of three cases with an oropharyngeal tumor; and had a more indolent, but frequently fatal, clinical course. The most frequent sites of biopsy-proven involvement in these patients were lymph nodes (three), the oropharynx (three), liver (three), bone marrow (three), transplanted kidney (three), colon (two), and central nervous system (two). EBV-specific antibody titers including anti-viral capsid antigen IgG, anti-viral capsid antigen IgM, anti-early antigen, and anti-Epstein-Barr nuclear antigen were serially measured in all patients. Four patients demonstrated serological evidence of a primary (one) or reactivation (three) EBV infection. No patient had significant changes in anti-early antigen or anti-Epstein-Barr nuclear antigen titers. All three patients tested for oropharyngeal shedding of EBV were positive. A touch imprint of one tumor was stained for the presence of Epstein-Barr nuclear antigen, and a majority of cells were positive. EBV complementary RNA/DNA filter hybridization and/or viral DNA/DNA reassociation analysis performed on tumor biopsy specimens in five patients demonstrated multiple EBV genome equivalents per cell in all eight specimens tested. Clinical, pathological, serological, and molecular hybridization studies provide substantial evidence that EBV was the cause of these lymphoproliferative disorders occurring after renal transplantation. Impaired host defenses allow the EBV-transformed B-lymphocytes to escape normal control mechanisms. This impairment is invariable and influenced by many factors resulting in the observed spectrum of disease. Cytogenetic changes, however, may also be important.