Metastatic tumors in the jaws: a retrospective study of 114 cases.

BACKGROUND: Malignancies involving the bones are metastatic tumors more commonly than primary tumors. In this retrospective study, the authors review metastatic disease in the jaws. METHODS: The authors retrieved cases of metastatic disease in the jaws over a 45-year period from the pathology archives at the University of Michigan School of Dentistry, Ann Arbor, and Indiana University School of Dentistry, Indianapolis. RESULTS: The authors conducted a retrospective analysis of 114 cases of metastatic disease in the jaws and found that approximately 60 percent of subjects had no history of malignancy. The sex distribution was equivalent. Mandibular predilection was more prominent in females than in males. Metastases from the breast were significantly greater than those from the lung and prostate (P < or = .05), the second and third most frequent sites, respectively. Women exhibited twice as many jaw metastases as did men 31 to 40 years of age and significantly fewer metastases than did men 71 to 80 years of age (P < or = .05). CONCLUSION: In the majority of cases, subjects had an undiagnosed primary cancer at the time the metastatic jaw disease presented. The most common site of origin of the primary cancer was the breast, when primary sites were considered independent of sex. CLINICAL IMPLICATIONS: Patients with metastatic disease in the jaws may have innocuous dental symptoms, such as pulpal or periodontal pain; therefore, clinicians will play a significant role in diagnosing the life-threatening disease.

TLR4 mediates LPS-induced VEGF expression in odontoblasts.

Lipopolysaccharide (LPS) from gram-negative bacteria cell walls such as Prevotella intermedia and Escherichia coli induce vascular endothelial growth factor (VEGF) expression in odontoblasts, but not in undifferentiated dental pulp cells. CD14 and TLR4 are responsible for LPS signaling in macrophages, but their expression levels and function in dental pulp cells are unknown. We showed here that murine odontoblast-like cells (MDPC-23) express CD14 and TLR4 by immunohistochemistry and flow cytometry. In contrast, undifferentiated dental pulp cells (OD-21) presented low or no expression of these two receptors. MDPC-23 cells showed CD14 and TLR4 up-regulation upon exposure to LPS, as determined by real time PCR. Dominant negative murine TLR4 (DN-mTLR4) transfected MDPC-23 cells did not show upregulated VEGF expression in response to LPS stimulation. These results demonstrate that odontoblast-like cells express CD14 and TLR4, and that LPS-induced VEGF expression is mediated, at least in part, by TLR4 signaling.

Adhesive resin and the hydrophilic monomer HEMA induce VEGF expression on dental pulp cells and macrophages.

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by inducing endothelial cell proliferation, migration and survival. Direct pulp capping with an adhesive resin system was shown to induce local increase in blood vessel density and lack of dentin bridging. However, the mechanisms involved in the increase in blood vessel density observed near the pulp exposures capped with an adhesive resin are largely unknown. OBJECTIVES.: To investigate the effect of an adhesive resin or one of its hydrophilic monomers (HEMA), in the expression of VEGF by pulp cells. METHODS.: Mouse odontoblast-like cells (MDPC-23), undifferentiated pulp cells (OD-21), gingival fibroblasts, and macrophages were exposed to SingleBond (3M) or to 0-1000nM HEMA. VEGF expression was evaluated by ELISA and semi-quantitative RT-PCR. RESULTS AND SIGNIFICANCE.: VEGF expression was upregulated in MDPC-23 cells exposed to HEMA (p<0.001) or to SingleBond (p<0.018), and in macrophages exposed to HEMA (p<0.001) or SingleBond (p=0.001). In contrast, VEGF expression remained unchanged in undifferentiated pulp cells (OD-21), or fibroblasts exposed to either HEMA or Single Bond (p>0.05). Treatment with SingleBond or HEMA did not affect VEGF expression at the mRNA level of any cell type evaluated here, suggesting that the induction of VEGF expression in these cells is regulated primarily at the post-transcriptional level. These findings suggest that VEGF is involved in the regulation of pulp neovascularization observed in response to the application of adhesive resins at site of pulp exposure.

Effect of lipopolysaccharides on vascular endothelial growth factor expression in mouse pulp cells and macrophages.

Vascular endothelial growth factor (VEGF), a potent pro-angiogenic factor, might regulate the neovascularization observed in the pulp of teeth with deep caries. The purpose of this in vitro study was to evaluate the effect of bacterial lipopolysaccharides (LPS) on VEGF expression in dental pulp cells. Mouse odontoblast-like cells (MDPC-23) or undifferentiated pulp cells (OD-21) were exposed to 0-20 microg ml-1Escherichia coli LPS or 0-80 microg ml-1Prevotella intermedia LPS. As controls, mouse macrophages or gingival fibroblasts were exposed to LPS, since these cells are known to secrete VEGF. The VEGF expression was evaluated by reverse transcriptase polymerase chain reaction or enzyme-linked immunosorbent assay. The baseline expression levels of VEGF protein were higher in MDPC-23 and OD-21 than in fibroblasts or macrophages. Vascular endothelial growth factor protein expression was upregulated in MDPC-23 and macrophages exposed to E. coli LPS, but not in OD-21 cells or fibroblasts. Higher concentrations of P. intermedia LPS were required to induce VEGF expression in MDPC-23 cells. Treatment with LPS did not affect VEGF expression at the mRNA level in any of the cells evaluated. These results demonstrate that bacterial LPS upregulates VEGF expression in odontoblast-like cells and macrophages, and suggest that the regulation of VEGF expression occurs primarily at a post-transcriptional level.

Malignant melanoma of the oral mucosa in a 17-year-old adolescent girl.

Mucosal melanomas of the oral cavity are rarely seen in the United States. The hard palate is the most common intraoral site. This unusual case occurred in the oral cavity of a 17-year-old Asian girl, who presented to her dentist with complaints of pain and swelling in the upper jaw. The lesion was distal and palatal to the maxillary left second molar, which was vital. Interestingly, the clinical presentation was a hyperplastic, tender lesion that bled when probed. Histopathologically, the biopsy demonstrated a sheet of spindle-shaped cells arranged in nests and fascicles. The nuclei were vesicular, oval to spindle-shaped, and some contained nucleoli that were distinguishable but not prominent. No melanin pigment was observed in the lesion. Tumor cells strongly expressed S100 protein, gp100 (HMB-45), and microphthalmia transcription factor, and variably expressed MART1, but not cytokeratins, CD34, or muscle-specific actin. The histopathologic features and immunohistochemical findings are consistent with a diagnosis of malignant melanoma.