SUMMARY:Inflammatory myofibroblastic tumor (IMT) is composed of myofibroblasts, plasma cells, and lymphocytes.Cytokines are possibly involved in its pathogenesis. Human herpesvirus-8 (HHV-8) encodes cell cycle regulatory and signaling proteins. A combination of nested PCR with several negative controls and Southern blot methods showed the presence of HHV-8 DNA in seven cases of IMT. Additionally, strong expression was demonstrated by in situ hybridization in many tumoral nuclei. Most of the myofibroblasts in all of the cases were immunoreactive for human IL-6 and cyclin D1. These cytokines probably have a paracrine action and may sustain myofibroblastic growth. HHV-8 could play an essential role in triggering IMT development by a local reactivation of viral lytic replication. The relationship between HHV-8 and immunosuppression status as the only associated cause for tumorigenesis should be revised. (Lab Invest 2000, 80:1121-1126.
The presence of human herpesvirus-8 DNA sequences, as well as an overexpression of human interleukin-6 and human cyclin D1 in myofibroblastic cells of inflammatory myofibroblastic tumor (inflammatory pseudotumor), has recently been reported. We describe the pattern of human herpesvirus-8 gene expression in five cases of pulmonary inflammatory myofibroblastic tumor. Reverse transcriptase-polymerase chain reaction (RT-PCR), with several positive and negative controls, was performed to detect mRNA of 11 open reading frames encoded by human herpesvirus-8 in lytic and latent stages of viral replicative cycle. We found molecular transcripts from ORF16, ORFK13, and ORF72 in the five cases and from ORFK2 in four of five neoplasms. The corresponding encoded proteins were human homologous oncoproteins (viral cyclin-D), inflammatory cytokines (viral IL-6), and inhibitors of apoptotic pathways (viral FLIP and viral Bcl-2), mostly expressed in a latent viral replicative stage. The rest of open reading frames examined included mainly lytic-associated genes and showed no expression. The spectrum of expressed viral genes is not the same as can be observed in Kaposi's sarcoma or multicentric Castleman's disease, suggesting that human herpesvirus-8 plays a different role in the pathogenesis of its associated diseases. These differences may be related to either cell-specific or immunologic host factors.
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