ReviewDiseases (Basel, Switzerland)2026
The Spectrum of Human Herpesvirus 8/Epstein-Barr Virus-Co-Positive Lymphoproliferations and Lymphomas.
Review in Diseases (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
BACKGROUND/
objectivesHuman herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is a gamma-2 herpesvirus implicated in a distinctive group of lymphoproliferative disorders (LPDs) and lymphomas. In some of these entities, lesional cells are concurrently infected with Epstein-Barr virus (EBV), a gamma-1 herpesvirus, raising important questions regarding viral cooperation in lymphomagenesis. This narrative review summarizes the clinicopathological spectrum and biological significance of HHV-8/EBV co-positive lymphoproliferations.
methodsWe provide a narrative synthesis of the biology of HHV-8 and EBV, including latent, abortive lytic, and productive lytic infection programmes and viral mechanisms involved in cell-cycle deregulation, apoptosis inhibition, immune evasion, and B-cell transformation. Major HHV-8-associated lymphoproliferative entities are reviewed within the current WHO-HAEM5 and International Consensus Classification frameworks, with particular attention to patterns of EBV co-infection and diagnostically atypical or overlapping lesions.
resultsPrimary effusion lymphoma, including its extracavitary presentation, is frequently EBV-positive, whereas HHV-8-positive germinotropic lymphoproliferative disorder is characteristically HHV-8/EBV dual-positive. In contrast, HHV-8-positive lesional cells in multicentric Castleman disease and HHV-8-positive diffuse large B-cell lymphoma are typically EBV-negative. True dual positivity requires demonstration of HHV-8 latency-associated nuclear antigen and EBV-encoded RNA within the same morphologically defined lesional cell population. Rare atypical cases show overlapping clinicopathological features among established entities.
conclusionsHHV-8/EBV co-positive lymphoproliferations comprise a biologically and diagnostically heterogeneous group. Although unusual overlapping cases suggest potential relationships among HHV-8-associated disorders, current evidence does not support a single continuous disease spectrum or a uniform mechanism of HHV-8/EBV cooperation.
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