Lymphoproliferative disorders with concurrent HHV8 and EBV infection: beyond primary effusion lymphoma and germinotropic lymphoproliferative disorder

Aims: Lymphoproliferative disorders (LPD) characterised by human herpesvirus 8 (HHV8) and Epstein–Barr virus (EBV) infection are rare and two entities are included in the World Health Organisation classification: primary effusion lymphoma (PEL) and germinotropic LPD. These two entities have very different clinicopathological presentations and prognosis. Here we describe two cases of HHV8-positive, EBV-positive lymphoma with clinicopathological features that are not consistent with either PEL or germinotropic LPD. Methods and results: Both patients were HIV-negative without a history of immunodeficiency. In the first case, the patient presented with localised axillary lymphadenopathy without any other symptoms. Biopsy showed lymphoma cells located predominantly in mantle zones with extension into interfollicular areas. Some follicles showed Castleman features, including lymphocyte-depleted germinal centres penetrated by sclerotic blood vessels and surrounded by concentric rings of small lymphocytes. Using immunohistochemistry, the lymphoma cells were positive for CD3 (weak), CD20 and HHV8. EBV was positive, as shown by in-situ hybridisation. The lymphoma cells were negative for CD138, immunoglobulin (Ig)M and kappa and lambda. In the second case, the patient presented with multi-compartmental lymphadenopathy and biopsy showed neoplastic cells that grew in a diffuse pattern with immunoblastic/plasmablastic morphology. Neoplastic cells were positive for both HHV8 and EBV, partially positive for CD20 and CD138 and negative for kappa and lambda. Conclusions: The description of these two cases suggests that the category of HHV8⁺ EBV⁺ LPDs is a spectrum, which not only includes PEL and germinotropic LPD, but also other cases that have overlapping but distinctive features.