Detection of EBV virus may be performed as stains in tissue sections in one of two ways: (1) EBV IHC or (2) EBER (EBV-encoded RNA) ISH. EBV IHC antibody reacts with the BNLF1 gene product that forms the latent membrane protein (LMP). This marker has limited sensitivity in the 30% range.
EBER expression is localized to the nucleus, while the IHC LMP stains the surface membrane.
Pitfalls
EBER expression can identify lymphocytes latently infected with EBV. Therefore, in CHL for example, the tumor cells must show expression for the case to be considered EBV-related. On the other hand IHC stains for LMP rarely mark latently infected cells in the background, but may show false positivity in poorly fixed tissue, cells in the nervous system, and some uninfected hematopoietic elements (eosinophils and plasma cells). False negative results are more common with IHC LMP in decalcified tissues.
Inter-observer agreement is greater for the interpretation of EBER compared to LMP.
EBV Expression Profile
- DLBCL – EBV is identified in cases of EBV+ DLBCL of the elderly.
- Hodgkin Lymphoma – Approximately 40% of Hodgkin lymphoma cases express EBV in the Hodgkin cells. (Mixed cellularity HL is ~70%+)
- Burkitt Lymphoma – Endemic form
- Nasopharyngeal Carcinoma
- Infectious Mononucleosis
Photomicrographs
References
American Journal of Clinical Pathology. 2002;117(2)