Assessing the Agreement of Light Microscopic Evaluation of Oral Lichen Planus Lesions With Associated Direct Immunofluorescence Evaluation.

Aim/objective: Assess agreement between light microscopy and direct immunofluorescence (DIF) for histopathologic evaluation of oral lichen planus (OLP). Methods: Records evaluated included 60 OLP, 16 lichenoid mucositis (LM), and 56 non-OLP/non-LM cases. Cases had both light microscopic and DIF evaluations. Histopathologic parameters of OLP included: (1) hydropic degeneration of the basal cell layer, (2) band-like lymphocytic infiltrate immediately subjacent to the epithelium, and (3) presence of Civatte bodies. Two calibrated examiners independently assessed light microscopic features. Examiners reviewed cases with discordant diagnoses to determine a consensus diagnosis. Intra-rater reliability (IRR), sensitivity, specificity, positive, and negative predictive values (PPV and NPV) were determined. Results: Of 132 patients, 72.7% were female, average age 61.9 (SD = 13.8). Most common sites were gingiva (37.9%), buccal mucosa (37.1%), and tongue (7.6%). IRR was 0.74 (95% CI: 0.40, 1.00) for the consensus diagnosis and 0.73 (95% CI: 0.39, 1.00) and 0.34 (95% CI: -0.03, 0.72) for the 2 examiners. Comparing consensus and definitive diagnoses: sensitivity of light microscopy: 0.32 (95% CI: 0.20, 0.45); specificity: 0.88 (95% CI: 0.78, 0.94); PPV: 0.68 (95% CI: 0.48, 0.84), and NPV: 0.61 (95% CI: 0.51, 0.70). Conclusion: Light microscopy alone is not a viable alternative to adjunctive DIF for diagnosis of OLP lesions.

Early detection of cherubism with eventual bilateral progression: a literature review and case report.

Cherubism is a rare familial disease of childhood that commonly affects the bilateral mandible and maxilla and typically resolves in adulthood. It has been shown to have a male predilection and has been mapped to the SH3 BP2 gene. Only 2 cases of unilateral cherubism have been documented in the literature; in the first case, the contralateral side was eventually affected. Although rare, unilateral cherubism presents a diagnostic dilemma. This case report describes a unique presentation of unilateral cherubism that progressed to affect the contralateral side and describes some of the considerations in the diagnosis and treatment of unilateral benign giant cell lesions of the jaws.

Standardized Rat Model Testing Effects of Inflammation and Grafting on Extraction Healing.

BACKGROUND: Loss of alveolar ridge width and height after tooth extraction is well documented, but models to evaluate ridge preservation are neither standardized nor cost-effective. This rat model characterizes the pattern of bone turnover and inflammation after extraction and bone grafting with or without local simvastatin (SIM). METHODS: Fifty retired-breeder rats underwent extraction of the maxillary right first molar and standard surgical defect creation under inhalation/local anesthesia. The left side of each animal served as unmanipulated control. Untreated groups (n = 8 to 9 per group) were compared (analysis of variance, t test) at days 0, 7, 14, and 28 for alveolar ridge height and width and for markers of inflammation and bone turnover by microcomputed tomography, histology, and enzyme-linked immunosorbent assay. Seventeen additional specimens had defects grafted with either bone mineralized matrix (BMM) or a BMM+SIM conjugate. RESULTS: Extraction-induced bone loss (BL) was noted on buccal, palatal, and interproximal height (P <0.05) and ridge width (P <0.01). Week 1 inflammation positively correlated with ridge height; thereafter, a more intense inflammatory reaction corresponded to reduction in alveolar bone height and density (r = 0.74; P <0.05; Spearman). BMM+SIM preserved the most interproximal bone height (P <0.01), increased ridge width and bone density (P <0.01), enhanced 7-day prostaglandin E2 (P <0.01), and reduced 28-day inflammation density (P <0.05). CONCLUSIONS: The standard defect used in the current study paralleled human postextraction alveolar BL. Defect grafting, especially BMM+SIM, reduced inflammation and preserved bone.

S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

Helping Dental Students Make Informed Decisions About Private Practice Employment Options in a Changing Landscape.

According to the 2014 American Dental Education Association (ADEA) Survey of Dental School Seniors, 45.3% of new graduates planned to enter private practice immediately after graduation; of those, while 65% planned to become an associate dentist in a private practice, 28.3% intended to enter a corporate group practice-the only category that saw an increase over the previous year. Current trends indicate that the number of new graduates choosing to enter some form of private practice without further education will continue to remain high, due in large part to the need to repay educational debt. In light of these trends, the question that must be asked is whether dental schools are optimally preparing students to make informed decisions regarding future employment options in the changing dental practice landscape. This article argues that dental schools should review their curricula to ensure graduates are being prepared for this changing environment and the increased business pressures associated with dental practice. Important considerations in preparing dental students to be successful in the process of selecting a practice model are identified.

Effect of dexamethasone prodrug on inflamed temporomandibular joints in juvenile rats.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) often causes inflammation of the temporomandibular joint (TMJ) and has been treated with both systemic and intra-articular steroids, with concerns about effects on growing bones. In this study, we evaluated the impact of a macromolecular prodrug of dexamethasone (P-DEX) with inflammation-targeting potential applied systemically or directly to the TMJ. METHODS: Joint inflammation was initiated by injecting two doses of complete Freund's adjuvant (CFA) at 1-month intervals into the right TMJs of 24 growing Sprague-Dawley male rats (controls on left side). Four additional rats were not manipulated. With the second CFA injection, animals received (1) 5 mg of P-DEX intra-articularly (n = 9), (2) 15 mg of P-DEX into the tail vein (n = 7), or (3) nothing in addition to CFA (n = 8). The rats were killed 28 days later and measured by radiography for ramus height (condylar superior to gonion inferior [CsGoInf]), by micro-computed tomography for condylar width (CW) and bone volume/standardized condylar volume (BV/CV), and by histology for retrodiscal inflammatory cells. Inflammation targeting of systemic P-DEX was confirmed by IVIS infrared dye imaging. Inflammation and bone growth were compared between groups using analysis of variance and Pearson's correlations. RESULTS: CFA caused a significant reduction in CsGoInf (p < 0.05), but neither route of P-DEX administration had an effect on CsGoInf or CW at CFA injection sites. BV/CV was significantly reduced in both inflamed and control condyles as a result of either steroid application (p < 0.05). The inflammatory infiltrate was overwhelmingly lymphocytic, comprising 16.4 ± 1.3 % of the field in CFA alone vs. <0.01 % lymphocytes in contralateral controls (p < 0.0001). Both P-DEX TMJ (10.1 ± 1.2 %) and systemic P-DEX (8.9 ± 1.7 %) reduced lymphocytes (p < 0.002). The total area of inflammatory infiltrate was significantly less in the systemic injection group than in the group that received CFA injections alone (2.6 ± 1.5 mm(2) vs. 8.0 ± 1.3 mm(2); p = 0.009), but not in the group that received intra-articular P-DEX (8.8 ± 1.2 mm(2)). CONCLUSIONS: High-dose systemic administration of inflammation-targeting P-DEX is more effective than an intra-articular injection in reducing TMJ inflammation, but both routes may affect TMJ bone density.

Mastl kinase, a promising therapeutic target, promotes cancer recurrence.

Mastl kinase promotes mitotic progression and cell cycle reentry after DNA damage. We report here that Mastl is frequently upregulated in various types of cancer. This upregulation was correlated with cancer progression in breast and oral cancer, poor patient survival in breast cancer, and tumor recurrence in head and neck squamous cell carcinoma. We further investigated the role of Mastl in tumor resistance using cell lines derived from the initial and recurrent tumors of the same head and neck squamous cell carcinoma patients. Ectopic expression of Mastl in the initial tumor cells strongly promoted cell proliferation in the presence of cisplatin by attenuating DNA damage signaling and cell death. Mastl knockdown in recurrent tumor cells re-sensitized their response to cancer therapy in vitro and in vivo. Finally, Mastl targeting specifically potentiated cancer cells to cell death in chemotherapy while sparing normal cells. Thus, this study revealed that Mastl upregulation is involved in cancer progression and tumor recurrence after initial cancer therapy, and validated Mastl as a promising target to increase the therapeutic window.

Malignant PEComa involving the mandible: report of a unique case.

We report a unique case of a malignant perivascular epithelioid cell neoplasm (PEComa) presenting as a slow-growing mandibular lesion in a 77-year-old Caucasian female. Primary osseous involvement by PEComas is rare. This is the first reported case of a malignant PEComa arising within the jaw. The patient is currently free of disease 2 years after treatment.

Effect of simvastatin injections on temporomandibular joint inflammation in growing rats.

PURPOSE: Juvenile idiopathic arthritis often affects the temporomandibular joint (TMJ), resulting in facial deformities, and intra-articular injections of anti-inflammatory steroids used in treatment may inhibit bone growth in the developing condyle. The purpose of this pilot study was to evaluate the anti-inflammatory properties of simvastatin (SIM), a bone anabolic drug, compared with the common steroid triamcinolone hexacetonide (TH) in experimental TMJ arthritis of growing rats. METHODS: Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 32 growing (4-week-old) Sprague-Dawley rats while simultaneously receiving 1) ethanol drug carrier, 2) 0.1 mg of SIM, 3) 0.5 mg of SIM, or 4) 0.15 mg of TH. Six rats had no treatment to the TMJ. Animals were euthanized 28 days later, and TMJs were decalcified and stained with hematoxylin-eosin. RESULTS: Histopathologic TMJ results showed that CFA injection along with drug carrier induced increased thickness of the articular layer on the head of the condyle and inflammation of the retrodiscal area (CFA and ethanol). Although both TH and SIM reduced the articular layer thickness, 0.5 mg of SIM was more effective at reducing subsynovial inflammation. CONCLUSIONS: Intra-articular simvastatin showed anti-inflammatory properties in this TMJ model, prompting its further study in the growing TMJ, where bone anabolic properties would be important.

A dentigerous cyst associated with bilaterally impacted mandibular canines in a girl: a case report.

INTRODUCTION: A dentigerous cyst is the most common developmental odontogenic cyst and is frequently noted as an incidental finding on radiographs. The most common teeth affected are impacted mandibular third molars and permanent maxillary canines. This case involves a dentigerous cyst encompassing the right and left impacted mandibular canines and crossing the midline. This is, to the best of our knowledge, the first reported case of a dentigerous cyst encompassing non-adjacent teeth and crossing the midline. CASE PRESENTATION: The patient presented to our orthodontic clinic for treatment of malocclusion. The patient was a 10-year, one-month-old Caucasian girl with a dentigerous cyst encompassing the right and left impacted mandibular canines and crossing the midline. CONCLUSION: This case involves an unusual clinical and radiographic presentation of a dentigerous cyst. It shows a new variant of presentation that medical professionals, specifically dentists and radiologists, should be aware of, since a dentigerous cyst crossing the midline has not been previously reported as far as we are aware. This additional knowledge is important for inclusion on differential diagnosis lists and aids in the development of a proper treatment plan.

Diagnosis and management of oral candidiasis.

Oral candidiasis is the most common fungal infection in both the immunocompetent and the immunocompromised populations. This article reviews the clinical presentations of the different forms of oral candidiasis, as well as the diagnosis and management.

Simvastatin application to augment facial jaw bone in a dog model: pilot study.

BACKGROUND: Locally injected simvastatin (SIM) has been shown to induce bone growth in rat models. The purpose of this study is to evaluate the effects of locally injected simvastatin in several human-like clinical situations in a beagle dog model. METHODS: Four beagle dogs completed the study and were used in a split-mouth design. Dehiscence defects of 5 × 3 mm were created bilaterally on the lateral aspect of the mandibular second premolar (PM2) mesial roots including removal of root cementum. At the same surgery, porous hydroxyapatite-collagen grafts with resorbable membranes with or without 10-mg SIM were placed buccal to the mandibular first molars (M1). One week later, three weekly local injections of 10-mg SIM in ethanol and contralateral ethanol alone were initiated at three sites through the buccal mucosa: 1) 6 mm apical to the cemento-enamel junction (CEJ) of the maxillary fourth premolar (PM4; thin bone over root); 2) 6 mm apical to the CEJ of PM2 (dehiscence defect); and 3) 10 mm distoapical to the CEJ of the maxillary canine (edentulous ridge). Dogs were euthanized 2 months after the final injections. Block sections were harvested and specimens were decalcified and stained with hematoxylin and eosin. Histomorphometry was performed using digitized photographs and analyzed with distribution-free rank tests. RESULTS: Regarding M1, the distance between CEJ and the alveolar crest was significantly more coronal in the SIM group (P = 0.038). Regarding the edentulous ridge, the width of new bone was significantly greater in SIM injection specimens (P = 0.0164). Regarding PM2, buccal bone in the dehiscence defects lacking periosteum was not augmented in the SIM group. Regarding PM4, the total width of bone 5 mm apical to the coronal height of contour (thin buccal bone covering the root) was significantly wider on the SIM side (SIM, 0.63 ± 0.53 mm; contralateral ethanol alone, 0.25 ± 0.19 mm; P = 0.0098). CONCLUSION: Locally injected SIM has the ability to induce modest amounts of new bone formation in closed injection sites over a periosteal surface.

Implications of drug dependence on dental patient management.

Drug abuse and dependence/addiction are complex health issues. A broad understanding of these problems is important in terms of dental patient management. Dental professionals should be knowledgeable in recognizing the symptoms of drug abuse and signs of drug-seeking behavior, while ensuring that patients still receive the best possible dental treatment. This article reviews several important characteristics of drug abuse and dependence and provides recommendations for patient management.

Oral histoplasmosis: an unusual presentation.

BACKGROUND: Histoplasmosis is a localized or systemic fungal infection which may present as an acute primary or "reactivation" infection in the setting of immunosuppression. Tumor necrosis factor alpha (TNF-alpha) antagonists, used in the management of rheumatoid arthritis and Crohn disease, have been linked to reactivation of quiescent histoplasmosis. Microscopically, granulomas are either not evident or are infrequent in histoplasmosis when associated with TNF antagonist therapy presumably due to the suppression of macrophage activity. METHODS AND RESULTS: This article describes an unusual presentation of oral histoplasmosis in a 75-year-old-woman patient on TNF-alpha antagonist, namely infliximab. Microscopically, cellular atypia resulted in a work-up to rule out lymphoma. Gomori's methenamine silver stain demonstrated Histoplasma capsulatum leading to a diagnosis of histoplasmosis. She was treated successfully with itraconozole. CONCLUSION: This is the first reported case, insofar as the authors are able to determine, of oral histoplasmosis, in a patient undergoing treatment with infliximab.

Injectable simvastatin in periodontal defects and alveolar ridges: pilot studies.

BACKGROUND: Topical injection of simvastatin in methylcellulose gel was shown to stimulate bone growth and inflammation over mouse calvaria and in rat mandible models. The purpose of these pilot studies was to evaluate the potential of locally injected simvastatin in human-sized periodontal defects. METHODS: Chronic periodontal defects were created bilaterally in seven 1-year-old beagle dogs: 3-walled intrabony defects distal of the mandibular second premolar and mesial of the fourth premolar and Class II furcation defects at the buccal furcation of the mandibular first molars. The edentulous space distal to the mandibular canine was left undisturbed. After 16 weeks of healing, defect sites were treated with scaling and root planing, and mandible sides were randomly selected to receive three weekly injections of 0.5 mg simvastatin in 30 microl methylcellulose gel and contralateral gel alone (n=3) or 2.0 mg simvastatin/methylcellulose gel and contralateral gel alone (n=4). Two months following drug application, block sections, including teeth and surrounding tissues, and submandibular lymph nodes were obtained for histomorphometric analysis. RESULTS: Two trends were noted in this pilot study: buccal edentulous ridge thickness was 29% greater with simvastatin, 0.5 mg, compared to gel alone (P=0.0845), and the simvastatin groups had bone-height loss in interproximal intrabony and furcation defects, but the length of new cementum in the interproximal intrabony defects was greater with simvastatin, 0.5 mg (0.35+/-0.14 mm), compared to gel alone (0.06+/-0.15 mm; P=0.069). No new cementum was found in furcations. CONCLUSIONS: Multiple injections of simvastatin are not appropriate for the treatment of intrabony or furcation defects. However, this approach shows potential to augment bone thickness in closed alveolar environments.

Functional activities and immunohistochemical cellular distribution of glutathione s-transferases in normal, dysplastic, and squamous cell carcinoma human oral tissues.

Clinical data show a strong correlation between tobacco and alcohol use and the development of oral squamous cell carcinoma (SCC). While this association implies that the oral mucosa actively metabolizes carcinogens, there is little information which depicts the carcinogen metabolizing enzymes within the oral cavity. Glutathione S-transferases (GSTs) primary function is to detoxify carcinogens by increasing their water solubility, GSTs represent key carcinogen metabolizing enzymes. Notably, individuals with a null phenotype for certain GST isoforms are at an increased risk to develop cancer. This study investigated the function and distribution of GSTs in human oral tissues. Our results from this pilot study showed a trend towards higher GST activities in SCC tissues relative to normal mucosa. Also, relative to normal tissues, the SCC and epithelial dysplasia samples showed a more intense and uniform GST intracellular distribution. GST activities are increased in many high grade cancers. Similarly, our data suggest that GST upregulation occurs in at least a subset of precancerous and malignant oral lesions.

Adenoid cystic carcinoma of the buccal vestibule: A case report and review of the literature.

Minor salivary gland tumors of the buccal vestibule are relatively rare. Adenoid cystic carcinoma is the fifth most common salivary gland malignancy following mucoepidermoid carcinoma, adenocarcinoma not otherwise specified (NOS), acinic cell adenocarcinoma and polymorphous low-grade adenocarcinoma (PLGA). Greater than half of adenoid cystic carcinomas occur in the parotid and submandibular glands. The most common intraoral site is the palate. Adenoid cystic carcinoma tends to have a protracted clinical course with wide infiltration and late distant metastases. We present a case of an adenoid cystic carcinoma of the buccal vestibule in a 59-year-old Caucasian female patient that she had been aware of for 15 years.

Chronic craniofacial dematiaceous fungal infection: a case report.

Curvularia is a saprobic dematiaceous mold that has been associated with a wide spectrum of human infection. In non-immunosuppressed patients, infections frequently involve the paranasal sinus, skin, and soft tissue, whereas systemic dissemination and endocarditis are extremely rare. The optimal antifungal therapy for Curvularia infection is not known, and responses to treatment with amphotericin B, miconazole, ketoconazole, terbinafine, and itraconazole have been reported. We describe a patient with an invasive dematiaceous fungal sinusitis who was immunocompetent and was infected with Curvularia. The patient was successfully treated with oral itraconazole by otolaryngology and the infectious disease service.

Clinical and microbiological efficacy of chlorine dioxide in the management of chronic atrophic candidiasis: an open study.

OBJECTIVE: To assess the clinical and microbiological efficacy of chlorine dioxide (ClO2) as a topical antiseptic for the treatment of chronic atrophic candidiasis in geriatric patients. PARTICIPANTS: Thirty patients with chronic atrophic candidiasis. METHODS: Patients were instructed to rinse the mouth with 0.8% ClO2 mouth rinse (DioxiDent) twice daily for one minute and to soak their dentures overnight in the ClO2 for 10 days. Patients were evaluated both clinically and microbiologically at baseline and after 10 days, and any significant side effects were recorded. The clinical appearance of the oral soft tissues was scored on a scale of 0-3 (0 indicating no clinical signs, 1 indicating involvement of < 25% of the palatal mucosa, 2 indicating involvement of 25-50% of the palatal mucosa, and 3 indicating marked erythema involving > 50% of the palatal mucosa). Microbiological testing was undertaken to determine the number of colony forming units (CFUs) of Candida albicans. RESULTS: ClO2 significantly improved the clinical appearance and microbial count (p < 0.001) after treatment, without significant side effects. Results showed marked improvement in the clinical appearance of the tissues after 10 days, with total resolution in the majority of cases. The total CFU/ml ranged from 15,000-53,000 at baseline and was reduced to < or = 500 after 10 days of treatment (p < 0.001). The mean clinical score was 2.50 at baseline, and was reduced to 0.17 after 10 days of treatment (p < 0.001). CONCLUSIONS: Within the limitations of this pilot study, the effectiveness of topical chlorine dioxide (0.8%) in the management of chronic atrophic candidiasis was demonstrated. ClO2 provided a safe and clinically effective option in the management of chronic atrophic candidiasis.