A Review of the Cytomorphology of Epstein-Barr Virus-Associated Malignancies

Abstract

The Epstein-Barr virus (EBV) is a member of the herpes family of viruses and is very common in humans. EBV is most often associated with infectious mononucleosis. However, it is estimated that 1% of tumors including lymphoproliferative, epithelial and mesenchymal are linked to EBV infection. EBV has a tropism for certain epithelial cells, lymphocytes and myocytes. Like other herpesviruses, EBV has both lytic and latent phases of infection. In the latent form, EBV-encoded genes ensure the survival of the viral genome, allowing it to circumvent the host’s immune surveillance by limited expression of viral proteins and carries with it the risk of neoplastic transformation. Cytologists are likely to encounter EBV-associated malignancies in cytology material but unlike other herpesviruses, EBV does not evoke a viral cytopathic effect. The manifestation of EBV-related tumors is also often variable depending upon the patient’s immune status. Therefore, knowledge of the patient’s EBV status and immune competence (e.g. HIV-infection or transplant-related immunosuppression) combined with the cytomorphology and results of ancillary studies are often all required to make a diagnosis of EBV-associated malignancy. This review discusses the unique cytomorphology and ancillary studies required to diagnose EBV-related neoplasms.

COX-2 induces lytic reactivation of EBV through PGE2 by modulating the EP receptor signaling pathway

“…COX-2 can be induced by several intracellular and extracellular factors including lipopolysaccharide (LPS), epidermal growth factor (EGF), and tumour necrosis factor (Font-Nieves et al, 2012; Medeiros et al, 2010; Yucel-Lindberg et al, 1999). Published studies have revealed a close association between COX-2 over-expression and EBV associated cancers (Michelow, Wright, and Pantanowitz, 2012; Murray and Young, 2001). A convincing positive correlation has been reported between COX-2 and the EBV viral protein LMP1.…”

Infectious mononucleosis and risk of breast cancer in a prospective study of women

“…[15, 16] In particular, one investigation considered whether IM, a manifestation of EBV acquisition in adolescence or early adulthood, may be related to breast cancer. [17] Investigators in this study used international and United States cancer registries to estimate a correlation between breast cancer and IM incidence (international, 0.74; SEER, 0.88).…”

Epstein–Barr virus encoded RNA detected by in situ hybridization using cytological preparations

“…The present study is the largest series to report the use of ISH for EBER to determine EBV status on different type of preparations (cell block sections and cytospin preparations) from different cytological samples (FNA and fluids), and in a patient population with various EBV‐related diseases and immune status. EBV is associated with many lymphoid and solid tissue malignancies in both immunocompetent and immunocompromised individuals and a positive or negative test has an important diagnostic, prognostic and therapeutic implication . Previous studies, although with smaller number of cases and limited to one specific EBV‐related condition, have shown similar results .…”