Abstract
BackgroundHuman herpesvirus‐8 (HHV8) is a lymphotropic virus associated with different lymphoproliferative disorders, including primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD), diffuse large B‐cell lymphomas, not otherwise specified, and the rare entity known as germinotropic lymphoproliferative disorder (GLPD). In PELs and GLPD the neoplastic cells also contain Epstein–Barr virus (EBV). In addition, occasional cases with atypical and overlapping features among these entities have been recognised, suggesting that the spectrum of the HHV8‐related lesions may not be fully characterised.AimsHere, we report two cases of lymphoproliferative disorder associated with HHV8 and EBV that further expand the spectrum of HHV8/EBV‐positive lymphoproliferative disease.Methods and resultsCase 1 represented HHV8/EBV‐positive extracavitary nodal PEL followed by pleural PEL. The striking characteristic of this case was the almost focal and intrasinusoidal localisation of the neoplastic cells and the association with Castleman’s disease features. In the second case, we found the entire spectrum of HHV8‐related disorders, i.e. MCD, GLPD, and PEL, coexisting in the same lymph node, underlining the variability, possible overlap and evolution among these entities. Both cases were well analysed with immunohistochemistry, determination of the EBV latency programme, and molecular analysis for clonality of immnoglobulin genes. In both patients, the disease followed an unexpected indolent course, both being still alive after 8 and 12 months, respectively.ConclusionOur findings represent further evidence of the overlap among HHV8/EBV‐positive lymphoproliferative disorders, and underline a grey zone that requires further study; they further confirm the experimental evidence that lytic EBV replication influences HHV8‐related tumorigenesis.
Highlights
Human herpesvirus-8 (HHV8) has been identified in multicentric Castleman’s disease (MCD),[5] in the rare entity known as germinotropic lymphoproliferative disorder (LPD) (GLPD),[6] in primary effusion lymphoma (PEL) and its solid variant [extracavitary PEL (EC-PEL)],7,8 and in HHV8-positive diffuse large B-cell lymphoma, not otherwise specified.[9]
We report two cases of LPD associated with HHV8 and Epstein–Barr virus (EBV) that further expand the spectrum of HHV8/EBV-positive lymphoproliferations[29,30,31,32,33,34,35,36,37,38,39] (Table S2)
HHV8/ EBV-positive LPDs probably represent a broad spectrum of lesions with overlapping features and possible evolution among different entities[29,30,31,32,33,34,35,36,37,38,39] (Table S3)
Summary
Since the discovery of human herpesvirus-8 (HHV8) as the causative agent of Kaposi’s sarcoma in 1994,1HHV8 has been identified in several different types of lymphoproliferative disorder (LPD), with distinctive clinicopathological features, including the propensity for Epstein–Barr virus (EBV) coinfection.[2,3,4]In particular, HHV8 has been identified in multicentric Castleman’s disease (MCD),[5] in the rare entity known as germinotropic LPD (GLPD),[6] in primary effusion lymphoma (PEL) and its solid variant [extracavitary PEL (EC-PEL)],7,8 and in HHV8-positive diffuse large B-cell lymphoma, not otherwise specified.[9]In particular, in PELs and GLPD the neoplastic cells contain EBV, which itself causes 1–2% of the total human cancer burden worldwide.[6,7]Except for GLPD, the majority of these disorders arise in human immunodeficiency virus (HIV)positive patients,[10,11] but cases in HIV-seronegative patients have been reported.[12,13] to what occurs with EBV (human herpesvirus-4),[14] the oncogenic transformation of HHV8 occurs following the initial infection, when the virus establishes a latent phase. Human herpesvirus-8 (HHV8) is a lymphotropic virus associated with different lymphoproliferative disorders, including primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD), diffuse large B-cell lymphomas, not otherwise specified, and the rare entity known as germinotropic lymphoproliferative disorder (GLPD). We found the entire spectrum of HHV8-related disorders, i.e. MCD, GLPD, and PEL, coexisting in the same lymph node, underlining the variability, possible overlap and evolution among these entities. Both cases were well analysed with immunohistochemistry, determination of the EBV latency programme, and molecular analysis for clonality of immnoglobulin genes. Conclusion: Our findings represent further evidence of the overlap among HHV8/EBV-positive lymphoproliferative disorders, and underline a grey zone that requires further study; they further confirm the experimental evidence that lytic EBV replication influences HHV8-related tumorigenesis
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