CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS High incidence of Kaposi sarcoma–associated herpesvirus–related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with Kaposi sarcoma–associated herpesvirus, also called human herpesvirus type 8 (KSHV/HHV8). Within a prospective cohort study on 60 HIVinfected patients with MCD, and a median follow-up period of 20 months, 14 patients developed KSHV/HHV8-associated non-Hodgkin lymphoma (NHL): 3 “classic” KSHV/HHV81 Epstein-Barr virus– positive (EBV1) primary effusion lymphoma (PEL), 5 KSHV/HHV81 EBV2 visceral large cell NHL with a PEL-like phenotype, and 6 plasmablastic lymphoma/leukemia (3/3 KSHV/HHV81 EBV2). The NHL incidence observed in this cohort study (101/1000 patient-years) is about 15-fold what is expected in the general HIV1 population. MCD-associated KSHV/HHV81 NHL fell into 2 groups, suggesting different pathogenesis. The plasmablastic NHL likely represents the expansion of plasmablastic microlymphoma from the MCD lesion and progression toward aggressive NHL. In contrast, the PEL and PEL-like NHL may implicate a different original infected cell whose growth is promoted by the cytokine-rich environment of the MCD lesions. (Blood. 2002;99:2331-2336)