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Analysis of the Human Herpesvirus 8 (HHV-8) Genome and HHV-8 vIL-6 Expression in Archival Cases of Castleman Disease at Low Risk for HIV Infection

David M. Menke MD, Amy Chadburn MD, Ethel Cesarman MD, Eric Green MD, James Berenson MD, Jonathan Said MD, Markus Tiemann MD, Reza Parwaresch MD, Stephan D. Thome MD
DOI: http://dx.doi.org/10.1309/7243-AV50-KJ28-V6J9 268-275 First published online: 1 February 2002


Lymph nodes from 44 patients with Castleman disease (CD) without risk factors for HIV infection were analyzed with polymerase chain reaction (PCR), in situ hybridization (ISH), and immunohistochemical analysis for human herpesvirus 8 (HHV-8) and viral interleukin-6 (vIL-6). PCR detected HHV-8 genome in 2 of 4 cases; ISH detected it in 9 of 16 cases. HHV-8 vIL-6 peptides were detected in 2 of 44 cases. vIL-6– and ISH-positive cells were found in large transformed and small lymphocytes of the follicular mantle, respectively. Of 9 cases of plasma cell (PC) CD that demonstrated HHV-8 genome by PCR or ISH, 1 expressed vIL-6. Clonal populations of PCs in CD by immunohistochemical analysis or immunoelectrophoresis of serum and urine were associated with neuropathy. HHV-8 vIL-6 detection was associated with poor survival and lack of HHV-8 IL-6, with low risk for subsequent lymphoma. Although HHV-8 genome was detected in a considerable number of patients with PC CD, vIL-6 expression was infrequent. Expression of HHV-8 vIL-6 in CD may indicate poor prognosis in patients at risk for lymphoma who may prospectively require more aggressive treatment. The lack of vIL-6 expression in CD with HHV-8 genome suggests that human IL-6 rather than vIL-6 may be the principal pathogenic cytokine.

Key Words:
  • Castleman disease
  • Human herpesvirus 8
  • Lymphoma