Regulation of olfactomedin 4 by Porphyromonas gingivalis in a community context.

At mucosal barriers, the virulence of microbial communities reflects the outcome of both dysbiotic and eubiotic interactions with the host, with commensal species mitigating or potentiating the action of pathogens. We examined epithelial responses to the oral pathogen Porphyromonas gingivalis as a monoinfection and in association with a community partner, Streptococcus gordonii. RNA-Seq of oral epithelial cells showed that the Notch signaling pathway, including the downstream effector olfactomedin 4 (OLFM4), was differentially regulated by P. gingivalis alone; however, regulation was overridden by S. gordonii. OLFM4 was required for epithelial cell migratory, proliferative and inflammatory responses to P. gingivalis. Activation of Notch signaling was induced through increased expression of the Notch1 receptor and the Jagged1 (Jag1) agonist. In addition, Jag1 was released in response to P. gingivalis, leading to paracrine activation. Following Jag1-Notch1 engagement, the Notch1 extracellular domain was cleaved by P. gingivalis gingipain proteases. Antagonism by S. gordonii involved inhibition of gingipain activity by secreted hydrogen peroxide. The results establish a novel mechanism by which P. gingivalis modulates epithelial cell function which is dependent on community context. These interrelationships have relevance for innate inflammatory responses and epithelial cell fate decisions in oral health and disease.

Ridge Augmentation Comparing a Cancellous Block Allograft to an Osteoinductive Demineralized Bone Matrix Allograft: A Randomized, Controlled, Blinded Clinical Trial.

Twenty-six patients with a horizontal ridge defect were entered into this 4-month randomized, controlled, blinded clinical trial to compare a cancellous block allograft to a demineralized bone matrix (DBM) allograft for ridge augmentation. Six patients were excluded from the study, leaving 20 for data interpretation. Both groups had a xenograft overlay and a collagen membrane. For the Block group there was a significant gain of 4.8 ± 1.9 mm (P = .00002; 95% confidence interval [CI]: 3.49 to 6.21), while the DBM group gained 4.6 ± 2.4 mm (P = .0002; 95% CI: 2.88 to 6.36). Vertical change was minimal for both groups (P > .05). The Block group had a mean of 40% vital bone while the DBM group had 35%.

A Comparison of the Effect of Barrier Membranes on Clinical and Histologic Hard and Soft Tissue Healing with Ridge Preservation.

Twenty patients completed this randomized, controlled, blinded clinical trial comparing ridge preservation with a bioabsorbable polylactic acid membrane (PLA group) compared to an acellular dermal matrix membrane guided bone regeneration (ADMG group). An intrasocket corticocancellous allograft plus a facial overlay xenograft was used for both groups. Final crestal ridge width was significantly greater for the ADMG group (P < .05). Soft tissue thickness, conversely, was thicker for the PLA group. Vertical ridge height change increased significantly for the midbuccal site of the ADMG group. Histologic evaluation showed high percentages of vital bone for both groups.

Ridge Preservation Comparing the Clinical and Histologic Healing of Membrane vs No-Membrane Approach to Buccal Overlay Grafting.

Twenty-four patients completed this randomized, controlled, blinded clinical trial comparing ridge preservation with a membrane (acellular dermal matrix graft [ADMG]) vs no membrane on buccal overlay graft technique. An intrasocket corticocancellous allograft with a facial overlay xenograft was used for both groups, and an ADMG was used as a membrane with guided bone regeneration in the ADMG group (control group). In the No Membrane group (test group), ADMG was used to cover only the occlusal surface for graft containment, with no membrane on the buccal overlay graft. Final crestal ridge width and vertical ridge height had no significant difference between groups (P > .05). Facial contour was preserved for the ADMG group compared to No Membrane group. Histologic examination showed a high percentage of vital bone for both groups with no significant difference between groups.

Ridge Augmentation Comparing an Allograft Plus Autogenous Bone Chips to an Osteoinductive Demineralized Bone Matrix: A Clinical and Histologic Study in Humans.

PURPOSE: The primary aim of this randomized, controlled, blinded, clinical trial was to compare a mix of particulate allograft and harvested autogenous particles (Autogenous) to an osteoinductive demineralized bone matrix (DBM) allograft on clinical and histologic outcomes for horizontal ridge augmentation procedure. MATERIALS AND METHODS: Fourteen patients with a horizontal ridge defect with at least 1 adjacent tooth were entered into this study. The test group of 7 subjects received corticocancellous particulate allograft (Mineross) mixed with autogenous bone chips (70:30) harvested using a bone scraper (SafeScraper TWIST). Seven subjects in the control group received DBM (Optecure-CCC). Both groups had a corticocancellous particulate allograft overlay and an acellular dermis membrane (ADMG) (AlloDerm GBR) to cover the grafts. RESULTS: For the Autogenous group, there was a gain of 3.5 ± 1.4 mm while the DBM group gained 3.8 ± 1.6 mm (P < 0.05). Vertical change was minimal for both groups (P > 0.05). The Autogenous group had a mean of 35% vital bone while the DBM had 39% (P > 0.05). CONCLUSIONS: Both treatments provided similar gain of ridge width and minimal loss of ridge height. The autogenous bone chips did not provide any additional benefit when compared with allograft alone that had lot verified osteoinductive activity.

Aggressive histologic features do not predict biologic behavior in melanotic neuroectodermal tumor of infancy.

While generally benign, occasional aggressive histologic features in the melanotic neuroectodermal tumor of infancy (MNTI) have been used to justify a diagnosis of malignancy; this could lead to overtreatment. We report a case with presumed aggressive histologic features that did not recur following conservative treatment. This adds evidence that histologic features are not predictive of clinical behavior in MNTI.

Viral DNA integration and methylation of human papillomavirus type 16 in high-grade oral epithelial dysplasia and head and neck squamous cell carcinoma.

This study evaluated the integration and methlyation of human papillomavirus type 16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of HPV16-positive hgOED (N = 19) and HNSCC (N = 15) were evaluated, along with three HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell lines. HgOED cases were stratified into three groups with increasing degrees of cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was higher and the E2/E6 ratio lower (indicating a greater tendency toward viral integration) in group 3 than in groups 1 or 2 (p = 0.002, 0.03). Methylation was not observed in hgOED cases and occurred variably in only three HNSCC cases (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated with higher levels of methylation. HgOED with increased cytologic change, now termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased viral load and a tendency toward DNA integration, suggesting a potentially increased risk for malignant transformation. More detailed characterization and clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in HNSCC carcinogenesis.

Effect of Lecture Attendance and Prerequisite Academic Outcomes on Dental Students' Oral Pathology Performance.

Decreased lecture attendance in undergraduate and health science professions education has been noted throughout the world. The limited study of the effect of lecture attendance on dental students' performance has yielded mixed results, with some studies finding a positive effect and others reporting no association. The aim of this study was to evaluate the effect of lecture attendance on dental students' final grades in an oral pathology course at one U.S. dental school. Due to a curriculum change, second- and third-year students (N=233) were concurrently enrolled in the spring 2016 oral pathology (OP) course. Students' course grades were compared to attendance percentage (Att), grades in prerequisite basic science (PBS) courses, and Academic Average and Total Science (TS) scores on the Dental Admission Test. The results showed that both Att (p=0.011) and TS score (p<0.001) were significant predictors of OP grade, while race, gender, and age were not. Students' grades in OP were moderately to strongly correlated with their grades in all PBS courses (p<0.001). These results suggest that lecture attendance in OP should be encouraged but viewed in light of the finding that it was not as strongly correlated as PBS course performance and was a weaker predictor than TS score. Students with lower TS scores and PBS course grades should be encouraged to use additional supports such as tutoring to improve their performance in OP.

Histologic variation in high grade oral epithelial dysplasia when associated with high-risk human papillomavirus.

OBJECTIVES: Reported cytologic alterations associated with high-risk human papillomavirus (HR-HPV) in oral epithelial dysplasia (HPV-OED) need further characterization. STUDY DESIGN: Archival cases of high-grade oral epithelial dysplasia (hgOED) (N = 38) were assigned a cytologic score (CS) based on the average number of mitotic, karyorrhectic, and apoptotic cells per high-power field. Three groups were then generated on the basis of increasing CS: Focal (group 1, N = 14), Intermediate (group 2, N = 12), and Diffuse (group 3, N = 12). Polymerase chain reaction-based HPV genotyping and p16 immunohistochemistry were performed. RESULTS: HR-HPV was found significantly more in group 3 (83.3%) compared with groups 1 and 2 (group 1&2; 42.9% and 41.7%, respectively; P = .047). HPV16 predominated in HR-HPV-positive cases (90.5%). By location, the tongue or the floor of mouth was associated with all groups (P = .04). Increasing CS was associated with a slightly younger age (P = .04) and increased expression of p16 (P = .005). CS and p16 expression were not sensitive but were highly specific predictors for HR-HPV presence. Based on limited follow-up information, HPV-OED does not differ in clinical aggressiveness compared with conventional OED. CONCLUSIONS: Increased CS in hgOED is strongly associated with HR-HPV (mostly HPV16) and p16 expression. CS and p16 expression are specific predictors of HR-HPV presence. Further molecular study and long-term follow-up of HPV-OED are needed.

Ridge Preservation Comparing a Nonresorbable PTFE Membrane to a Resorbable Collagen Membrane: A Clinical and Histologic Study in Humans.

PURPOSE: The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. MATERIALS AND METHODS: All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. RESULTS: The change in horizontal crestal ridge width was -1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost -2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was -1.2 ± 1.5 for the CM group, whereas the PTFE group lost -0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. CONCLUSION: The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.

Human papillomavirus detection in histologic samples of multifocal epithelial hyperplasia: a novel demographic presentation.

OBJECTIVE: Human papillomavirus (HPV) typing of oral lesions microscopically consistent with multifocal epithelial hyperplasia (MEH) was performed to identify potential novel clinical presentations. STUDY DESIGN: MEH (N = 22 lesions, 17 patients) and squamous papilloma control samples (N = 9 lesions, 9 patients) were compared by using polymerase chain reaction-based HPV genotyping. Student's t tests were used to compare continuous characteristics. RESULTS: Of the study cases, 86.4% of MEH and only 11% of controls were positive for HPV (P = .0002). In MEH lesions, 45.5% contained HPV32, 36.4% HPV6, and 4.5% HPV40. MEH lesions were mostly multifocal (50%) and occurred in HIV-negative patients (81.3%). They predominated on the labial/buccal mucosa (63.3%), and there were significant differences between groups by anatomic site (P < .0001). HPV32, but not HPV6, was detected in known HIV-positive patients. CONCLUSIONS: A novel clinical presentation of MEH associated with HPV32 in HIV-negative, middle-aged to older adults is reported here. One case with HPV40 is the first to be reported. Future detection protocols should include HPV32, as it may be currently overlooked.

Topical application of a mucoadhesive freeze-dried black raspberry gel induces clinical and histologic regression and reduces loss of heterozygosity events in premalignant oral intraepithelial lesions: results from a multicentered, placebo-controlled clinical trial.

PURPOSE: Approximately 30% higher grade premalignant oral intraepithelial neoplasia (OIN) lesions will progress to oral cancer. Although surgery is the OIN treatment mainstay, many OIN lesions recur, which is highly problematic for both surgeons and patients. This clinical trial assessed the chemopreventive efficacy of a natural product-based bioadhesive gel on OIN lesions. EXPERIMENTAL DESIGN: This placebo-controlled multicenter study investigated the effects of topical application of bioadhesive gels that contained either 10% w/w freeze-dried black raspberries (BRB) or an identical formulation devoid of BRB placebo to biopsy-confirmed OIN lesions (0.5 g × q.i.d., 12 weeks). Baseline evaluative parameters (size, histologic grade, LOH events) were comparable in the randomly assigned BRB (n = 22) and placebo (n = 18) gel cohorts. Evaluative parameters were: histologic grade, clinical size, and LOH. RESULTS: Topical application of the BRB gel to OIN lesions resulted in statistically significant reductions in lesional sizes, histologic grades, and LOH events. In contrast, placebo gel lesions demonstrated a significant increase in lesional size and no significant effects on histologic grade or LOH events. Collectively, these data strongly support BRB's chemopreventive impact. A cohort of very BRB-responsive patients, as demonstrated by high therapeutic efficacy, was identified. Corresponding protein profiling studies, which demonstrated higher pretreatment levels of BRB metabolic and keratinocyte differentiation enzymes in BRB-responsive lesions, reinforce the importance of local metabolism and differentiation competency. CONCLUSIONS: Results from this trial substantiate the LOH reductions identified in the pilot BRB gel study and extend therapeutic effects to significant improvements in histologic grade and lesional size.

Platelet-rich plasma-assisted guided bone regeneration for ridge augmentation: a randomized, controlled clinical trial.

BACKGROUND: Platelet-rich plasma (PRP) contains a number of biologically active growth factors, and previous studies have reported conflicting ridge augmentation results. The primary aim of this randomized, controlled, masked, clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP. METHODS: Thirty-two patients with an edentulous ridge defect were sequentially entered into the study; four were excluded from data analysis. Fourteen patients received a cancellous allograft (CAN group) and the other 14 received a cancellous allograft mixed with PRP (PRP group). All 28 grafted sites were covered with a resorbable polylactide membrane. After elevation of a full-thickness flap, horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest. Vertical ridge dimensions were measured from a tooth-supported stent. All sites were reentered at 4 months, and a trephine core was obtained for histologic analysis before implant placement. RESULTS: The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm, whereas the PRP group gained 2.9 ± 1.0, and the difference was statistically significant between groups (P <0.05). The percent vital bone was 36% ± 14% for the CAN group compared with 51% ± 15% for the PRP group and was statistically significant between groups (P <0.05). Loss of augmented ridge width was 34% ± 17% for the CAN group and 28% ± 17% for the PRP group (P >0.05). CONCLUSION: These clinical and histologic findings suggest that PRP enhanced bone regeneration and resulted in increased horizontal bone gain and percentage vital bone.

Recurrent gingival fibrous lesions: comparison of 2 cases and potential need for additional classification.

Historically, the classification of localized gingival fibrous lesions has been inconsistent, leading to multiple naming schemes and confusion among pathologists. Currently, lesions are broadly grouped into localized hyperplastic lesions and true neoplasms. Although some cases are clearly defined histologically (i.e., peripheral ossifying fibroma, peripheral odontogenic fibroma), another set of "reactive" fibrous lesions exhibit overlapping histologic features including nondistinctive fibrosis and inflammation. This group can exhibit recurrence, classically related to a local stimulus. However, when local factors are absent, recurrence suggests inherent neoplastic potential. Herein, we describe 2 recurrent fibrous gingival masses, one of which reportedly recurred 3 times with no obvious inciting agent. The histologic appearance of both lesions was similarly distinctive but not well classifiable, while the immunohistochemical profile indicated divergent lesions. This highlights the need for further study of recurrent gingival fibrous lesions to better predict independent growth potential.

Ridge preservation comparing socket allograft alone to socket allograft plus facial overlay xenograft: a clinical and histologic study in humans.

BACKGROUND: Previous studies of ridge preservation showed a loss of ≈18% or 1.5 mm of crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, masked clinical trial is to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft. METHODS: Twelve patients who served as positive controls received an intrasocket mineralized cancellous allograft (socket group), and 12 patients received the same socket graft procedure plus buccal overlay cancellous xenograft (overlay group). Horizontal ridge dimensions were measured with a digital caliper, and vertical ridge changes were measured from a stent. Before implant placement, at 4 months, a trephine core was obtained for histologic analysis. RESULTS: The mean horizontal ridge width at the crest for the socket group decreased from 8.7 ± 1.0 to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (P <0.05), whereas the same measurement for the overlay group decreased from 8.4 ± 1.4 to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (P >0.05). The overlay group was significantly different from the socket group (P <0.05). Histologic analysis revealed that the socket group had 35% ± 16% vital bone, and the overlay group had 40% ± 16% (P >0.05). CONCLUSIONS: The overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The socket and overlay groups healed with a high percentage of vital bone.

Oral atypical cellular blue nevus: an infiltrative melanocytic proliferation.

The atypical cellular blue nevus is an extremely rare nevomelanocytic lesion which lacks precise histologic characterization in the current literature. Given the potential for significant architectural and cytologic overlap with melanoma, further study, including molecular analysis, is needed. This is the first description of an atypical cellular blue nevus of the oral cavity.

Pathology of the jaw: the importance of radiographs.

High-quality radiographs are essential in diagnosing pathology of the jaw. When appropriate radiographs are not submitted to the pathologist along with a biopsy specimen, misdiagnosis and mismanagement may occur. In this case study, we highlight the complementary value of panoramic and intraoral radiographs in allowing a definitive diagnosis of a mixed lesion of the jaw and preventing inappropriate treatment. Although many general dental practitioners tend to refer potential bony pathology, they should acquire and communicate high-quality radiographic information to specialty providers so that a precise diagnosis can be made.

Allelic imbalance in oral lichen planus and assessment of its classification as a premalignant condition.

OLP is a relatively common immune-mediated mucosal condition with a predilection for middle-aged women. Although classified as a premalignant condition, this classification remains controversial. Using stringent diagnostic criteria, some authors have found that OLP patients are not at increased risk for oral SCC. Credible but limited genetic evidence also indicates that epithelial tissues from OLP patients diagnosed using stringent criteria differs from premalignant or malignant oral lesions but is similar to epithelium from benign oral lesions. To further investigate this genetic line of evidence, biopsy specimens diagnosed as fibroma, OLP, low-grade dysplasia, high-grade dysplasia, and SCC were retrieved from the archives of the Oral Pathology Consultants at the Ohio State University. Using laser capture microdissection, tissue of interest was captured from each case and DNA subsequently extracted. Fluorescently labeled PCR primers were used to amplify DNA at 3 tumor suppressor gene loci (3p14.2, 9p21, and 17p13) and evaluated for LOH or microsatellite instability (MSI). OLP was found to be significantly different from low-grade dysplasia, high-grade dysplasia, and SCC when LOH/MSI was found at more than 1 loci (P = .011, P = .032, P = .003), but not different from benign fibromas (P = .395). In agreement with previous studies, well-documented cases of OLP diagnosed using stringent criteria exhibit a genetic profile more similar to a benign or reactive process than a premalignant/malignant one. These findings do not support the classification of OLP as a premalignant condition.

Basal cell carcinoma of the buccal mucosa in a patient with nevoid basal cell carcinoma syndrome.

Basal cell carcinoma (BCC) of the oral cavity is a controversial lesion with clinical and histopathologic features that overlap with those of peripheral ameloblastoma (PA). Ber-EP4, a cell surface glycoprotein preferentially expressed in BCC of the skin, has been suggested as a useful marker to support the diagnosis of oral BCC.This study presents a case of intraoral BCC arising in the anterior buccal mucosa of a patient with nevoid basal cell carcinoma syndrome (NBCCS), which represents a previously unreported clinical finding, to our knowledge. Histopathologic and immunohistochemical features of the case were compared to examples of PA, conventional intraosseous ameloblastoma, sporadic cutaneous BCC and cutaneous BCC from NBCCS patients. Ber-EP4 expression by the oral tumor was distinct from both peripheral and intraosseous forms of ameloblastoma and was identical to cutaneous BCC in both sporadic and syndromic settings.

Primary mucin-producing tumours of the salivary glands: a clinicopathological and morphometric study.

AIMS: To determine clinicopathological and morphometric features that discriminate between mucin-producing primary salivary gland carcinomas. MATERIALS AND RESULTS: Fifteen mucin-producing tumours were stratified into five colloid carcinomas (CCs), four mucinous cystadenocarcinomas (MCAs), three mucin-rich salivary duct carcinomas (SDCs) and three mucin-rich mucoepidermoid carcinomas (MECs). The mean patient age was 70, 58, 43 and 63 years for CC, MCA, SDC and MEC, respectively. Eleven of 15 patients were female. The majority of CC cases originated from major salivary glands; MCA showed a predilection for the minor salivary glands. No disease-related mortality was observed in the CC group; one patient died in the MCA group, and one in the SDC group. Receiver-operating characteristic curve analysis revealed an optimal cut-off point of 17% of the tumour cells in contact with stroma that best distinguished between the CC and MCA. Histomorphometric measurements revealed that CC was best differentiated from MCA by smaller nuclear size and more regular chromatin. CONCLUSIONS: Strict morphological criteria of CC coupled with assessment of the tumour cell/stroma relationship and the nuclear features facilitate discrimination between mucinous tumours of salivary gland.