María L. Paparella

Reactive lesions of peri-implant mucosa associated with titanium dental implants: a report of 2 cases

The aim of this study was to report 2 novel clinical cases of reactive lesions of the peri-implant mucosa associated with titanium dental implants where metal-like particles were observed histologically. In both cases, the lesions were diagnosed as epulis, based on clinical evidence. Extirpation biopsies were carried out. Case 1 was diagnosed as pyogenic granuloma and case 2 as peripheral giant cell granuloma. The presence of metal-like particles in the tissues suggests that the etiology of the lesions might be related to the corrosion process of the metal structure. This is the first case of pyogenic granuloma to be reported in association with dental implants. All clinical cases of soft tissue lesions associated with implants should be reported to contribute to the understanding of the etiology and pathogeny of these lesions.

Oral Mucosa Tissue Response to Titanium Cover Screws

BACKGROUND Titanium is the most widely used metal in dental implantology. The release of particles from metal structures into the biologic milieu may be the result of electrochemical processes (corrosion) and/or mechanical disruption during insertion, abutment connection, or removal of failing implants. The aim of the present study is to evaluate tissue response of human oral mucosa adjacent to titanium cover screws. METHODS One hundred fifty-three biopsies of the supra-implant oral mucosa adjacent to the cover screw of submerged dental implants were analyzed. Histologic studies were performed to analyze epithelial and connective tissue as well as the presence of metal particles, which were identified using microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were studied using immunohistochemical techniques. The surface of the cover screws was evaluated by scanning electron microscopy (SEM). RESULTS Forty-one percent of mucosa biopsies exhibited metal particles in different layers of the section thickness. Particle number and size varied greatly among specimens. Immunohistochemical study confirmed the presence of macrophages and T lymphocytes associated with the metal particles. Microchemical analysis revealed the presence of titanium in the particles. On SEM analysis, the surface of the screws exhibited depressions and irregularities. CONCLUSIONS The biologic effects seen in the mucosa in contact with the cover screws might be associated with the presence of titanium or other elements, such as aluminum or vanadium. The potential long-term biologic effects of particles on soft tissues adjacent to metallic devices should be further investigated because these effects might affect the clinical outcome of the implant.

Exfoliative Cytology and Titanium Dental Implants: A Pilot Study

BACKGROUND Oral exfoliative cytology is a diagnostic method that involves the study of cells exfoliated from the oral mucosa. Ions/particles released from metallic implants can remain in the peri-implant milieu. The aim of the present study is to assess the presence of metal particles in cells exfoliated from peri-implant oral mucosa around titanium dental implants. METHODS The study comprised 30 patients carrying titanium dental implants, who had neither a metallic prosthesis nor metal restorations in neighboring teeth. Individuals undergoing orthodontic therapy and those who had oral piercing were also excluded from the study. The study sample included patients with and without peri-implantitis. Cytologic samples of the peri-implant area were collected. Samples of the marginal gingiva on the contralateral side of the implant were taken from the same individuals to serve as control. Cytologic analysis was performed using light microscopy. Titanium concentration was determined using inductively coupled plasma-mass spectrophotometry. RESULTS Metal-like particles were observed inside and outside epithelial cells and macrophages in cytologic smears of peri-implant mucosa of both patients with and without peri-implantitis. No particles were found in the control cytologic samples. The concentration of titanium was higher in the peri-implantitis group compared with the group without peri-implantitis; no traces of titanium were observed in controls. CONCLUSIONS Regardless of an inflammatory response, ions/particles are released from the surface of the implant into the biologic milieu. Exfoliative cytology is a simple technique that may be used to detect metal particles in cells exfoliated from the peri-implant mucosa.

Osteosarcoma of the jaw: an analysis of a series of 74 cases

To analyse a series of cases of osteosarcoma of the jaw.

Expression of ezrin and metastatic tumor antigen in osteosarcomas of the jaw

Aims and background Ezrin is a membrane-cytoskeleton linker protein involved in regulation of the growth and metastatic behavior of cancer cells. Metastatic tumor antigen (MTA) is a potential metastasis-associated protein. The objective of this study was to evaluate the expression of ezrin and MTA and their correlation with clinico-pathological features in osteosarcomas of the jaw. Methods We analyzed ezrin and MTA protein levels by immunohistochemistry in 31 osteosarcomas of the jaw. Results The mean age at diagnosis was 39 years and half of the patients were male. The mandible (n = 19) was more frequently involved than the maxilla (n = 12). The predominant histological type was chondroblastic (58.1%) and 24 patients (77.4%) were classified as having a high grade of malignancy. Immunoreactivity for ezrin was identified in 6 of 31 cases (19.4%), while 77.4% displayed expression of MTA. All ezrin-positive patients had high-grade tumors. The high-grade tumors (n = 24) had a higher rate of MTA expression (42.9% vs 87.5%). Expression of ezrin and MTA was not significantly different according to age, sex, tumor site, histological type, and tumor ploidy. Follow-up information was available for 13 patients, with a mean follow-up time of 26.7 months (range, 6–48 months). At the time of last follow-up, 5 (38.5%) patients had died of disease and 8 patients (61.5%) were alive with no evidence of disease. Expression of ezrin and MTA was not significantly different according to the follow-up data. Conclusions In our study, high-grade tumors had a higher rate of ezrin and MTA expression. This expression pattern indicates that ezrin and MTA positivity can be additional prognostic markers in osteosarcoma of the jaw.

Histopathological features of osteonecrosis of the jaw associated with bisphosphonates

lomas show a CD163 pattern different from those of the other two granuloma types. Interestingly, Th2-type schistosomiasis-induced granulomas and FB-induced granulomas did not show any significant staining difference. As Th2 responses are thought to have antiinflammatory actions, it is feasible that proinflammatory activity against inert, non-degradable FB material is down-regulated by the host after a phase of recognition. This fits with the notion that the memory component of adaptive immunity is absent in FBinduced granulomas. We were not able to investigate spatial and temporal differences in the expression of the studied markers, as this information can hardly be obtained from human studies. We cannot rule out the possibility that CD163 expression might be different in Th1-mediated and Th2-mediated granulomas at different points in time. The present results obtained with human tissue are in accordance with established rodent models for these diseases, and provide some rationale for the idea that the so-called non-immunologically granulomas provoke an active anti-inflammatory response by the host that has Th2 characteristics and, despite the historical classification, have also to be considered as ‘immunological’.

Impact through time of different sized titanium dioxide particles on biochemical and histopathological parameters

Due to corrosion, a titanium implant surface can be a potential source for the release of micro (MPs) and nano-sized particles (NPs) into the biological environment. This work sought to evaluate the biokinetics of different sized titanium dioxide particles (TiO2 ) and their potential to cause cell damage. Wistar rats were intraperitoneally injected with 150 nm, 10 nm, or 5nm TiO2 particles. The presence of TiO2 particles was evaluated in histologic sections of the liver, lung, and kidney and in blood cells at 3 and 12 months. Ultrastructural analysis of liver and lung tissue was performed by TEM, deposit concentration in tissues was determined spectroscopically, and oxidative metabolism was assessed by determining oxidative membrane damage, generation of superoxide anion (O2(-)), and enzymatic and non-enzymatic antioxidants. TiO2 particles were observed inside mononuclear blood cells and in organ parenchyma at 3 and 12 months. TiO2 deposits were consistently larger in liver than in lung tissue. Alveolar macrophage O2(-) generation and average particle size correlated negatively (p < 0.05). NPs were more reactive and biopersistent in lung tissue than MPs. Antioxidant activity, particularly in the case of 5 nm particles, failed to compensate for membrane damage in liver cells; the damage was consistent with histological evidence of necrosis.

Osteosarcoma of the Jaws

Osteosarcoma of the jaw is rare considering that its incidence varies between 5 % and 13 % of total osteosarcomas. It accounts for 10 % of primary aggressive and malignant tumors of the jaws and for 8 % of all malignant lesions including metastatic and lymphoproliferative tumors. It differs from conventional osteosarcoma of long bones in a number of aspects (age of onset, predominant differentiation pattern, grade of malignancy, prognosis, clinical course, response to treatment, cause of death).

Impairing squamous differentiation by Klf4 deletion is sufficient to initiate tongue carcinoma development upon K-Ras activation in mice

Oral squamous cell carcinoma (SCC) is among the most prevalent cancers in the world and is characterized by high morbidity and few therapeutic options. Like most cancers, oral SCC arises from a multistep process involving alterations of genes responsible for balancing proliferation and differentiation. Among these, Krϋppel-like factor 4 (Klf4) suppresses cell proliferation and promotes differentiation and thus helps to maintain epithelial homeostasis. However, the prevailing role of Klf4 in maintenance of normal homeostasis in oral epithelium has not been established in vivo. Here, we used an inducible oral-specific mice model to selectively ablate Klf4 in the oral cavity. We generated K14-CreER(Tam)/Klf4 (f/f) mice that survived to adulthood and did not present overt phenotype. However, histologically these mice showed dysplastic lesions, increased cell proliferation and abnormal differentiation in the tongue 4 months after induction, supporting a homeostatic role of Klf4 in the oral epithelia. Furthermore, by breeding these mutants with a transgenic line expressing at endogenous levels K-ras (G12D), we assessed the role of disrupting differentiation gene programs to the carcinogenesis process. The K14-CreER(TAM)/K-ras (G12D)/Klf4 (-) (/-) mice rapidly develop oral SCC in the tongue. Thus, our findings support the emerging notion that activation of differentiating gene programs may represent a barrier preventing carcinogenesis in epithelial cells harboring oncogenic mutations, and thus that molecules acting upstream and downstream of Klf4 may represent components of a novel tumor-suppressive pathway.

Nucleolar organizer regions (AgNOR) and subepithelial vascularization as field cancerization markers in oral mucosa biopsies of alcoholic and smoking patients

OBJECTIVE The aim of this study was to show that variations in nucleolar organizer regions (AgNOR) and the increase in subepithelial vascularization could reveal changes related to markers of field cancerization in alcoholic and smoking patients who have not yet expressed clinical or histological malignant lesions. STUDY DESIGN Quantitative variations in epithelial AgNOR and in the vascularization of the underlying connective tissue were assessed by image analysis in histologically normal biopsy specimens from alcohol drinkers and smoking patients (DS). AgNORs were evidenced by silver staining and vessel walls were labeled by immunohistochemical demonstration of the CD34 antigen. Samples of oral mucosa of nonalcoholic, nonsmoking patients (NDS) obtained during surgical procedures served as controls. Eight parameters related to number, volume, and shape of nuclei and AgNORs, and 4 parameters related to number and diameter of vascular sections were evaluated. Differences between DS and NDS groups were statistically evaluated by means of ANOVA test and posterior Bonferroni comparisons. RESULTS The morphometric analysis revealed more irregular-shaped AgNORs in the superficial and suprabasal layers of the oral mucosa of DS patients. The suprabasal layers also exhibited a significantly larger number of AgNORs. The normal oral mucosa of DS patients exhibited a greater vascular density, with predominance of small-caliber blood vessels underlying the basement membrane. CONCLUSION The variations in AgNOR and epithelial vascularization would be practical biomarkers to evaluate changes underlying the augmented risk of cancerization in oral mucosa.