Plasmablastic lymphoma in an elderly immunocompetent patient.

Plasmablastic lymphoma (PBL) is a distinct type of diffuse B cell lymphoma that typically occurs in the oral cavity of patients with HIV infection or immunodeficiency status. PBL is characterized by its plasmablastic morphology and an immunophenotype indicative of a plasma cell differentiation. We present a case of a 75-year-old HIV-negative and Epstein-Barr virus (EBV)-negative patient presenting with an isolated oral cavity mass. The tumor consisted of a monotonous proliferation of undifferentiated large cells with relatively abundant cytoplasm, eccentrically located round nuclei with prominent nucleoli and numerous mitoses. Immunohistochemically, these cells were negative for CD45 and B cell antigens, while they showed diffuse positivity of CD138 and focal staining for epithelial membrane antigen (EMA), indicating plasma cell differentiation. Based on these histopathological and immunohistochemical characteristics, we diagnosed it as PBL. The patient received chemotherapy and is alive with locally persistent disease 3 years after diagnosis. To date, only several cases of oral PBL have been reported in HIV-negative, EBV-negative and immunocompetent patients. PBL should be included in the differential diagnosis of oral mass lesions and careful evaluation of the morphology and awareness of the existence of this uncommon type of lymphoma can lead to a correct diagnosis.

A novel fusogenic herpes simplex virus for oncolytic virotherapy of squamous cell carcinoma.

BACKGROUND: R849 is a neurovirulent γ134.5 gene-deficient form of herpes simplex virus type 1 (HSV-1) and has LacZ genes at the deleted sites of the γ134.5 gene. HF is a spontaneously occurring, fusogenic HSV-1 strain. The purpose of this work was to generate a virus that has the syncytial character of HF, while preserving the γ134.5 gene inactivation profile of R849 virus. RESULTS: Vero cells were infected with R849 and HF simultaneously and two viruses, RH1 and RH2, expressing the LacZ gene and inducing extensive cell fusion were selected. A polymerase chain reaction (PCR)-based analysis suggested that one copy of the γ134.5 gene is lost in RH1, whereas both copies are lost in RH2, and that the γ134.5 gene is replaced by a R849-derived DNA fragment with the LacZ gene. These viruses produced larger plaques and more progeny than the parental viruses. Infection with RH2 decreased the viability of oral squamous cell carcinoma (SCC) cells most strongly. When RH2 was injected into xenografts of oral SCC in nude mice, multinucleated cells were produced and the growth of the tumors was suppressed significantly. CONCLUSION: These results indicate that novel oncolytic HSV-1 vectors can be produced with the genetic background of the oncolytic HSV-1 HF, and that RH2 is deficient in γ134.5 genes and shows extensive cytopathic effects in oral SCC cells. RH2 may be useful in oncolytic virotherapy for oral SCC.

Combined oncolytic virotherapy with herpes simplex virus for oral squamous cell carcinoma.

BACKGROUND: The effect of dual infection with herpes simplex virus type 1 (HSV-1) mutants on human oral squamous cell carcinoma (SCC) cells was examined. MATERIALS AND METHODS: Human oral SCC cells were infected with gamma1(34.5) gene-deficient HSV-1 R849 and HSV-1 HF that has multiple mutations and induces cell fusion. Cell viability was measured by LDH release assay. Athymic mice were injected with oral SCC cells into the buccal region to induce subcutaneous tumors. RESULTS: Oral SCC cells were infected with R849, followed by infection with R849 or HF. Virus production was elevated by both strains of HSV-1. Although the release of LDH from R849-infected cells was increased by secondary infection with R849 or HF, the effect of HF was more remarkable. When nude mouse tumors were treated with R849, HF, R849+R849, or R849+HF, treatment with R849+HF was the most effective. CONCLUSION: These results suggest that fusion-inducing virus HF enhances the oncolytic ability of gamma1(34.5) gene-deficient HSV-1 and provides a rationale for using fusogenic viruses as enhancing agents