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Hodgkin Lymphoma & Epstein-Barr virus (EBV): In about 40% of classic Hodgkin lymphomas (cHL), the Hodgkin and Reed-Sternberg (HRS) cells are latently infected by EBV. The EBV tumor status varies with the histologic subtype and epidemiologic factors. EBV infection can be documented in about 75% of mixed cellularity and lymphocyte depleted, 40% of lymphocyte rich, 10-25% of nodular sclerosis, and only 5% of nodular lymphocyte predominant Hodgkin lymphomas.

Patients with history of infectious mononucleosis (IM) have an increased incidence of cHL. There are many morphologic similarities between IM and cHL. EBV is most often identified in cHL in children and older adults, in resource-poor countries, and in association with HIV infection (approaching 100%).

HRS cells are clonally infected, suggesting that EBV infection is an early event; however, EBV is not mandatory for the development of cHL and EBV-negative cases do occur. Multiple copies of EBV genome are present in episomal (non-integrated) form in the tumor cells at multiple involved sites. EBV-infected cells strongly express the oncoprotein LMP-1 which functions as TNF receptor and constitutively activates NF-κB and JAK/STAT signaling pathways and upregulates anti-apoptosis genes.

EBV can be demonstrated by immunohistochemistry for LMP-1 (latent membrane protein-1) or by in-situ hybridization for EBER (EBV-coded early RNAs; shown in this image) in formalin-fixed paraffin-embedded tissues. In-situ hybridization for EBER is most sensitive; however, it may be positive in infected, "bystander" lymphocytes in healthy carriers who may harbor the virus in a small number of latently infected B cells.

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