Response of Central Giant Cell Granuloma of the Jaw to Imatinib.

Central giant cell granuloma of the jaw (CGCJ) can be locally aggressive and result in facial and dental deformity. A child with CGCJ was treated surgically and with denosumab with a response but life-threatening toxicity. Imatinib, a tyrosine kinase inhibitor, was prescribed based on clinical similarities between CGCJ and cherubism, for which Imatinib has been effective. Within 2 months, a computed tomographic scan showed significant ossification, which increased over the following 8 months. This case suggests that tyrosine kinase inhibitors may be an effective option, and one with limited toxicity, for CGCJ.

Expression of ETS1 and LEF1 in salivary glands of Sjögren syndrome patients.

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease affecting exocrine glands, thereby causing dry mouth and eyes (sicca). Our objective was to determine the expression of pSS pathogenic biomarker MMP9 and its putative transcription factors ETS1 and LEF1, in labial salivary glands of pSS patients. METHODS: Sicca patients were assigned to three groups based on focus score (FS): non-pSS sicca (i.e., GR1 [FS = 0] and GR2 [0 < FS < 1]) and pSS (i.e., GR3 [FS ≥ 1]). We determined the mRNA and protein expression of MMP9, ETS1, and LEF1 in salivary gland biopsies. Also, ETS1-CD4 and LEF1-CD4 co-expression analyses were performed. RESULTS: The mRNA expression of MMP9, ETS1, and LEF1 was upregulated in GR3 compared to GR1 (p < 0.01). Most GR3 salivary gland areas had moderate to high MMP9, ETS1, and LEF1 protein expression compared to GR1 and GR2. Further, ETS1-CD4 and LEF1-CD4 dual staining demonstrated that both salivary gland epithelial cells and lymphocytic infiltrates had increased levels of ETS1 and LEF1. Moreover, there was a strong correlation between ETS1(+)-CD4(-) and LEF1(+)-CD4(-) cells. CONCLUSION: These results suggest, for the first time, a concerted increase in ETS1 and LEF1 expression in salivary gland epithelial cells of pSS patients that is reflective of the etiopathogenesis of pSS.

Incidental findings from cone beam computed tomography of the maxillofacial region: a descriptive retrospective study.

OBJECTIVE: To evaluate the type and prevalence of incidental findings from cone beam computed tomography (CBCT) of the maxillofacial region. Findings are divided into those that require (i) intervention/referral, (ii) monitoring, and (iii) no further evaluation. METHODS: Three hundred consecutive CBCT scans conducted in the University of North Carolina School of Dentistry Oral and Maxillofacial Radiology Clinic from January 1 to August 31, 2008 were retrospectively reviewed. Findings were categorized into airway, soft tissue calcifications, bone, temporomandibular joint (TMJ), endodontic, dental developmental, and pathological findings. RESULTS: A total of 272 scans revealed 881 incidental findings (3.2 findings/scan). The most prevalent was airway findings (35%) followed by soft tissue calcifications (20%), bone (17.5%), TMJ (15.4%), endodontic (11.3%), dental developmental (0.7%), and pathological (0.1%). 16.1% required intervention/referral, 15.6% required monitoring, and the remainder (68.3%) required neither. CONCLUSION: This study underscores the need to thoroughly examine all CBCT volumes for clinically significant findings within and beyond the region of interest.

Malignant Lymphoproliferative Disorders of the Oral and Maxillofacial Region: Report of Two Institutions.

BACKGROUND: Report of the incidence of malignant hematologic neoplasms in the oral cavity according to the experience of the two oral and maxillofacial pathology institutions in North Carolina, USA. METHODS: A 10-year retrospective review was carried out in the records of patients at ECU SoDM and UNC Adams SoD. Age, sex, location of the lesion, clinical impression, initial diagnosis, and the expression immunohistochemical and molecular markers were recorded for each subject. All diagnoses were reviewed according to the 2016 revision of the WHO classification of lymphoid neoplasms. RESULTS: A total of 318 records from both institutions were reviewed. Seventy males and 68 females with an average age of 60.7 comprised the study population. The most common neoplasm encountered was plasma cell myeloma, followed by diffuse large B-cell lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. We encountered primarily intraosseous tumors, with the posterior mandible and posterior maxilla being the most common locations. Twelve cases were identified initially as a periapical radiolucency. CONCLUSION: Our findings are concurrent with the existing literature regarding epidemiologic data. However, the type and location of tumors encountered do not, as the most common lymphoma in the oral cavity is diffuse large B-cell lymphoma, typically present in soft tissue. To aid in diagnosis and treatment, the collection of data should continue over time so that eventually, a more specific diagnostic profile of North Carolina residents with these neoplasms can be made.

SARS-CoV-2 infection of the oral cavity and saliva.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

Decellularized pulp matrix as scaffold for mesenchymal stem cell mediated bone regeneration.

Scaffolds that are used for bone repair should provide an adequate environment for biomineralization by mesenchymal stem cells (MSCs). Recently, decellularized pulp matrices (DPM) have been utilized in endodontics for their high regenerative potential. Inspired by the dystrophic calcification on the pulp matrix known as pulp stone, we developed acellular pulp bioscaffolds and examined their potential in facilitating MSCs mineralization for bone defect repair. Pulp was decellularized, then retention of its structural integrity was confirmed by histological, mechanical, and biochemical evaluations. MSCs were seeded and proliferation, osteogenic gene expression, and biomineralization were assessed to verify DPM's osteogenic effects in vitro. MicroCT, energy-dispersive X-ray (EDX), and histological analyses were used to confirm that DPM seeded with MSCs result in greater mineralization on rat critical-sized defects than that without MSCs. Overall, our study proves DPM's potential to serve as a scaffolding material for MSC-mediated bone regeneration for future craniofacial bone tissue engineering.

Working collaboratively across schools to promote oral health education through interprofessional education.

PURPOSE: The Association of American Medical Colleges and American Dental Education Association have identified oral health knowledge, skills, and attitudes shared by both medical and dental professionals. Although oral health was deemed an essential competency for medical practitioners, our state struggled to ensure learners received proper training. This training deficit resulted in conducting a needs assessment and implementing an oral health interprofessional module at our schools. METHODS: First-year medical students and clinical faculty were emailed surveys in 2016 to obtain baseline information. A team of faculty and students from the Schools of Medicine and Dentistry reviewed the curriculum to determine where to augment oral health content. An oral health module to teach a basic head, neck, and oral examination to first-year medical students during their patient-centered care small-group sessions was implemented and evaluated. RESULTS: Only 13.6% of faculty respondents were aware of national oral health competency recommendations, and <50% rated oral health important for primary care physicians (PCPs) to include in history, physical exam, or oral health counseling. On baseline, ≤25% of PCP respondents reported integrating the listed skills in their practice, and most indicated lacking expertise to teach oral health. Teaching sessions were rated helpful by students and faculty. After the teaching sessions, ratings on the importance of including oral health significantly increased from baseline. CONCLUSION: Collaboration between Schools of Dentistry and Medicine successfully integrated oral health into medical school curriculum and improved the tutors' attitudes of its importance.

Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis.

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS-CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection and implicates saliva in viral transmission.

Desmoplastic fibroma associated with tuberous sclerosis: case report and literature review.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that affects the skin, brain, kidneys, and other organ systems. It may exhibit a wide spectrum of clinical manifestations. Desmoplastic fibroma (DF) of the jaw is a rare benign myofibroblastic neoplasm. Less than 10 cases of DF associated with TSC have been published previously. We report a new case of a maxillary DF in a 12-year-old girl with TSC. The presentation, diagnostic process, and management of this case are discussed, and the literature is reviewed for the additional cases of DF associated with TSC; 7 previously reported cases are summarized. Small sample size limits conclusions, but there may be differences in the presentations of DF of the jaws in patients with TSC vs those in the general population. DF of the jaws may be a manifestation of TSC, and the authors propose surveillance panoramic radiographs every 2 to 3 years in patients with TSC.

Interprofessional Education: Oral Health in the Medical Curriculum.

Schools of medicine and dentistry on the same geographical campus have an opportunity to promote oral health by training physicians to become more skilled in screening for oral disease in addition to counseling and referring patients to dental health professionals.

AAOMP Case Challenge: a non-expansile radiolucency of the posterior mandible.

A 14-year-old Caucasian female was referred by her orthodontist with a non-expansile radiolucent lesion associated with impacted tooth #31.

Transcriptome Variability in Keratocystic Odontogenic Tumor Suggests Distinct Molecular Subtypes.

Keratocystic Odontogenic Tumor (KCOT) is a locally aggressive developmental cystic neoplasm thought to arise from the odontogenic epithelium. A high recurrence rate of up to 30% has been found following conservative treatment. Aggressive tumor resection can lead to the need for extensive reconstructive surgery, resulting in significant morbidity and impacting quality of life. Most research has focused on candidate-genes with a handful of studies employing whole transcriptome approaches. There is also the question of which reference tissue is most biologically-relevant. This study characterizes the transcriptome of KCOT using whole genome microarray and compare it with gene expression of different odontogenic tissues ("dentome"). Laser capture microdissection was used to isolate the neoplastic epithelial tissue in 20 cases. KCOT gene expression was compared with the "dentome" and relevant pathways were examined. Cluster analysis revealed 2 distinct molecular subtypes of KCOT. Several inflammatory pathways were activated in both subtypes. The AKT pathway was activated in one subtype while MAP kinase pathway was activated in the other. Additionally, PTCH1 expression was downregulated in both clusters suggesting involvement in KCOT tumorigenesis. In conclusion, this study provides new insights into the transcriptome of KCOT and highlights pathways that could be of diagnostic and prognostic value.

Ameloblastoma Phenotypes Reflected in Distinct Transcriptome Profiles.

Ameloblastoma is a locally invasive benign neoplasm derived from odontogenic epithelium and presents with diverse phenotypes yet to be characterized molecularly. High recurrence rates of 50-80% with conservative treatment in some sub-types warrants radical surgical resections resulting in high morbidity. The objective of the study was to characterize the transcriptome of ameloblastoma and identify relevant genes and molecular pathways using normal odontogenic tissue (human "dentome") for comparison. Laser capture microdissection was used to obtain neoplastic epithelial tissue from 17 tumors which were examined using the Agilent 44 k whole genome microarray. Ameloblastoma separated into 2 distinct molecular clusters that were associated with pre-secretory ameloblast and odontoblast. Within the pre-secretory cluster, 9/10 of samples were of the follicular type while 6/7 of the samples in the odontoblast cluster were of the plexiform type (p < 0.05). Common pathways altered in both clusters included cell-cycle regulation, inflammatory and MAPkinase pathways, specifically known cancer-driving genes such as TP53 and members of the MAPkinase pathways. The pre-secretory ameloblast cluster exhibited higher activation of inflammatory pathways while the odontoblast cluster showed greater disturbances in transcription regulators. Our results are suggestive of underlying inter-tumor molecular heterogeneity of ameloblastoma sub-types and have implications for the use of tailored treatment.

Biological assessment of a calcium silicate incorporated hydroxyapatite-gelatin nanocomposite: a comparison to decellularized bone matrix.

Our laboratory utilized biomimicry to develop a synthetic bone scaffold based on hydroxyapatite-gelatin-calcium silicate (HGCS). Here, we evaluated the potential of HGCS scaffold in bone formation in vivo using the rat calvarial critical-sized defect (CSD). Twelve Sprague-Dawley rats were randomized to four groups: control (defect only), decellularized bone matrix (DECBM), and HGCS with and without multipotent adult progenitor cells (MAPCs). DECBM was prepared by removing all the cells using SDS and NH4OH. After 12 weeks, the CSD specimens were harvested to evaluate radiographical, histological, and histomorphometrical outcomes. The in vitro osteogenic effects of the materials were studied by focal adhesion, MTS, and alizarin red. Micro-CT analysis indicated that the DECBM and the HGCS scaffold groups developed greater radiopaque areas than the other groups. Bone regeneration, assessed using histological analysis and fluorochrome labeling, was the highest in the HGCS scaffold seeded with MAPCs. The DECBM group showed limited osteoinductivity, causing a gap between the implant and host tissue. The group grafted with HGCS+MAPCs resulting in twice as much new bone formation seems to indicate a role for effective bone regeneration. In conclusion, the novel HGCS scaffold could improve bone regeneration and is a promising carrier for stem cell-mediated bone regeneration.

Use of archived biopsy specimens to study gene expression in oral mucosa from chemotherapy-treated cancer patients.

OBJECTIVES: Oral mucositis caused by cancer chemotherapy can result in significant clinical complications. There is a strategic need to accelerate the delineation of the pathobiology. This proof-of-principle study was designed to demonstrate the feasibility of studying archived oral mucosal specimens to further delineate oral mucositis pathobiology. MATERIALS AND METHODS: Twenty-nine formalin-fixed and paraffin-embedded tissue blocks of 25-year-old oral mucosa autopsy specimens from cancer chemotherapy patients were studied. Standardized technology was utilized, including RNA isolation and amplification, array hybridization, and gene expression analysis. RESULTS: A predominance of DNA damage in buccal mucosal basal keratinocytes was observed. Data comparing basal cells from buccal vs. gingival mucosa identified differential gene expression of host responses in relation to pathways relevant to oral mucositis pathogenesis, including responses to cancer-associated inflammation. CONCLUSIONS: This proof-of-principle study demonstrated that archived oral mucosal specimens may be a potentially valuable resource for the study of oral mucositis in cancer patients.

In vivo assessment of osseous wound healing using a novel bone putty containing lidocaine in the surgical management of tooth extractions.

Objective. This preclinical pilot study evaluated the systemic, radiographic, and histological responses to bone putty containing lidocaine in a canine tooth extraction model. Methods. In five beagle dogs the right mandibular premolars were extracted and sockets grafted with (1) xenograft particulate bone and a collagen sponge plug (control), (2) bone putty alone, (3) bone putty mixed with xenograft (3 : 1), or (4) xenograft sandwiched between bone putty. At 6 weeks post-op, the systemic and local responses were evaluated using a blood chemistry panel, micro-CT, and histological analyses. Results. No significant differences in blood chemistries were noted at 6 weeks postgrafting compared to baseline. Sockets grafted with either bone putty formulation demonstrated comparable radiographic and histologic evidence of bone healing compared to control sockets. Conclusions. Our preclinical results indicate that this bone putty appears to be a safe biocompatible device that may be useful in the postoperative management of tooth extractions.

The spectrum of gnathic osteosarcoma: caveats for the clinician and the pathologist.

Seven expansile jaw lesions in patients ranging from 7 to 63 years are presented to illustrate diagnostic and management issues pertaining to cases ultimately proven to be gnathic osteosarcoma (GO). Six of the cases in our series were low-grade osteoblastic and one high-grade chondroblastic. None of our cases exhibited the characteristic "sunburst" radiopaque appearance described for GO. All of our cases displayed cortical expansion and one showed development of diastema. Two occurred in the maxilla and five in the mandible. Two of the patients with mandibular lesions presented initially with pain; all other patients were asymptomatic. Lack of pain resulted in a delay in diagnosis due to postponement of consultation or biopsy. Two cases underwent initial shallow non-representative biopsies, requiring a second biopsy for definitive diagnosis, further delaying treatment. Those biopsies were initially interpreted as pyogenic granuloma and peripheral ossifying fibroma, respectively. GO should always be considered in the differential diagnosis of expansile jaw lesions. Bone biopsies of lesions exhibiting pain and expansion of cortical plates should include medullary bone in order to minimize sampling error. In addition, all rapidly growing or painful exophytic bone lesions, and presumed soft tissue lesions that may involve underlying bone, should be examined histopathologically, and receive clinical and radiographic follow-up until complete resolution or healing is evident, regardless of the diagnosis. Based on the positive outcomes of the patients in our series, the prognosis of GO appears to be relatively favorable when compared to other sarcomas and osteosarcomas of long bones.