HHV-8 is associated with a plasmablastic variant of Castleman disease that is linked to HHV-8–positive plasmablastic lymphoma

Abstract

Castleman disease (CD) is a lymphoproliferative disorder of unknown etiology that is associated with the development of secondary tumors, including B-cell lymphoma. Human herpesvirus 8 (HHV-8) (Kaposi's sarcoma–associated herpesvirus) sequences have been described in some cases of multicentric Castleman disease (MCD). Using a monoclonal antibody against an HHV-8–latent nuclear antigen, we show that HHV-8 is specifically associated with a variant of MCD in which HHV-8–positive plasmablasts that show λ light-chain restriction localize in the mantle zone of B-cell follicles and coalesce to form microscopic lymphomas in some cases. Furthermore, we show that the frank plasmablastic lymphoma that develops in patients with this plasmablastic variant of MCD is also positive for HHV-8 and λ light chain. Plasmablastic lymphoma associated with MCD is a new disease entity associated with HHV-8 infection.

Distinct Roles for Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 in the Structure and Production of a Primate Gammaherpesvirus

“…T he gammaherpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV), is the causative agent of three human malignancies, most notably Kaposi's sarcoma (KS), an AIDS-defining disease (10,11,21,22,44,45,58,59). Since even the best source of KSHV virions tends to yield titers that are often less than 10E5/ml (1), primate homologs such as rhesus monkey rhadinovirus (RRV), which favor lytic rather than latent infection in culture, often serve as a model system for studying virus structure and protein composition (16,50).…”

Serous fluid cytology of multicentric Castleman’s disease and other lymphoproliferative disorders associated with Kaposi sarcoma‐associated herpes virus: a review with case reports

“…14 of large plasmablastic cells exhibiting a restricted monotypic lambda phenotype. 15 The bone marrow of patients with MCD contains characteristic MCD lymphoid follicles containing KSHV-positive plasmablasts and scattered interstitial KSHV-positive plasmablasts. 16 KSHV-positive plasmablasts are polyclonal in all cases of MCD and in the majority of plasmablastic ÔmicrolymphomasÕ.…”

The pathobiology of Kaposi’s sarcoma: advances since the onset of the AIDS epidemic

“…The LANA-1 monoclonal antibody allows the identification of all types of KS lesions, KSHV-positive lymphomas, and is present in scattered cells in the mantle zone of MCD. 15 Polymerase chain reaction (PCR) has been extensively used as a method to identify KSHV. PCR has the ability to detect the presence of the virus in varying tissue forms, frozen or fresh, and in over 95% of all KS disease variants.…”

“…11 Since the isolation of the virus, KSHV has been found in all forms of KS previously mentioned 12 as well as in primary effusion lymphomas (PEL), 13 in multicentric Castleman's disease (MCD) 14 and in a plasmablastic lymphoma variant associated with MCD. 15 Many of these KSHV-associated diseases have been found to co-exist in the same host. 16…”