When to use in situ hybridization for the detection of Epstein-Barr virus: a review of Epstein-Barr virus-associated lymphomas

Epstein-Barr (EBV) is the first virus supposed to be causative for human neoplasm. To date, list of EBV-associated lymphomas includes Burkitt lymphoma, Hodgkin lymphoma, pyothorax-associated lymphoma, primary effusion lymphoma, nasal type extranodal natural killer/T cell lymphoma, plasmablastic lymphoma, immunodeficiency-associated lymphoproliferative disorders, and lymphomatoid granulomatosis. In these diseases, presence of EBV could be detected at protein level by immunohistochemistry and at genetical level by polymerase chain reaction and in situ hybridization both applicable on routinely processed formalin-fixed, paraffin-embedded specimens. Clonality of EBV-infected cells could be examined by Southern blot analysis. EBV status examined using these ancillary diagnostic tools were informative for diagnosis of lymphoma, especially diseases developing under immunodeficient condition and diseases showing polymorphous histology with or without large multinucleated cell like a Hodgkin–Reed Sternberg cell. Comprehensive evaluation of clinical presentation, histology, immunohistochemistry, genetic aberration, and EBV status enable accurate diagnosis of EBV-associated lymphoma.