Human herpesvirus 8-related Castleman disease in the absence of HIV infection.

BACKGROUND: Castleman disease (CD) in the context of human immunodeficiency virus (HIV) infection is well described. It is almost always multicentric (MCD) and linked to human herpesvirus 8 (HHV-8). There are limited published data surrounding HHV-8-related CD among HIV-negative patients. METHODS: From January 1995 through June 2012, we identified in a single center 18 HIV-seronegative patients with HHV-8-related CD. We report on their clinical, pathological, and laboratory features. RESULTS: All cases were multicentric. Patients were aged 42-83 years and were referred with a relapsing remitting syndrome of fever (94%), constitutional symptoms (100%), peripheral lymphadenopathy (100%), splenomegaly (72%), hepatomegaly (50%), and edema (28%). Kaposi sarcoma was observed in 9 cases. Anemia and serum markers of inflammation were present in all cases. Polymerase chain reaction for HHV-8 DNA was positive on blood samples in all cases, whereas only 12 of 16 patients tested had positive HHV-8 serology at diagnosis. All cases showed the classic histological features of MCD, and LANA-1 immunostaining identified HHV-8-infected plasmablasts in 16 of 16 tested cases. Reactive hemophagocytic syndrome (44%), autoimmune hemolytic anemia (33%), and lymphoma (22%) were the commonest associated complications. Remission was obtained with etoposide in 13 of 15 cases. Rituximab allowed prolonged remission off therapy in 10 cases. Death occurred in 3 patients not treated with rituximab. These features were similar to those described in HIV-positive HHV-8-related MCD. Comparison between these 18 cases and 12 HIV-negative HHV-8-unrelated MCD cases showed marked discrepancies. CONCLUSIONS: HHV-8-associated MCD may be considered as a single clinicopathological entity regardless of HIV status.