Epstein-Barr virus (EBV) is the causative agent of in-fectious mononucleosis, and it may also be found in a wide variety of benign and malignant lesions including oral hairy leukoplakia, inflammatory pseudotumor, Hodgkin's disease, non-Hodgkin's lymphoma, nasopharyngeal carcinoma, and gastric carcinoma. Molecular testing is increasingly important in the diagnosis and monitoring of patients affected by these diseases. In biopsy tissues, molecular detection of EBV-encoded RNA transcripts by in situ hybridization remains the gold standard for proving that a histopathological lesion is EBV-related. EBV-encoded RNA hybridization and EBV LMP1 immunostains are used routinely to detect latent EBV in tissues affected by posttransplant lymphoproliferative disorder (PTLD) or in enlarged nodes from patients with infectious mononucleosis. Traditional serology is the best test for evaluating acute versus remote infection in healthy individuals. High serological titers serve as a tumor marker for some EBV-related malignancies, but titers are not a dependable tumor marker in immunocompromised hosts. EBV viral load testing by quantitative DNA amplification of blood samples is a promising new laboratory test that has proven useful for early diagnosis and monitoring patients with PTLD. Recent studies suggest a role for EBV viral load testing in nasopharyngeal carcinoma, Hodgkin's disease, and AIDS patients with brain lymphoma. Further research is needed to define more fully the clinical utility of viral load tests in the full spectrum of EBV-associated diseases. Gene expression profiling is on the horizon as a means to improve subclassification of EBV-related diseases and to predict response to therapy. In subsequent decades, EBV has been linked to a wide variety of benign and neoplastic diseases. Nasopharyngeal carcinomas and posttransplant lymphoproliferative disorders are nearly always EBV-associated, whereas several other tumors, such as Hodgkin's disease, nonHodgkin's lymphoma, lymphoepithelioma-like carcinoma, gastric adenocarcinoma, and several types of sarcoma, are less uniformly EBV-associated. 2-7 EBV causes benign transient lymphoproliferative lesions at the time of primary infection, and it is found in a benign lesion of the tongue called oral hairy leukoplakia. 8,9 Patients affected by these benign or malignant diseases may benefit from laboratory detection of EBV to confirm their diagnosis or to monitor disease burden after the initiation of therapy.Laboratory detection of EBV is accomplished in several ways (Table 1), and recent progress has focused on the molecular analysis of viral DNA and RNA. In situ hybridization has long been considered the gold standard for detecting tumor-associated viral infection, and EBV viral load assays are now being adopted for clinical evaluation of tumor burden in affected patients. This review article summarizes the pathobiology of EBV infection and describes the clinical laboratory tests that are used to assist in diagnosis and monitoring of patients with EBV-related diseases.
The ...