Dysbiosis of saliva microbiome in patients with oral lichen planus.

BACKGROUND: Oral microbiota is not only important for maintaining oral health but also plays a role in various oral diseases. However, studies regarding microbiome changes in oral lichen planus (OLP) are very limited. To the best of our knowledge, there has been only two studies investigating salivary microbiome changes in OLP. Therefore, the purpose of this study was to identify the characteristic microbial profile in the saliva of OLP patients, with or without erosive lesions, and compare that with recurrent aphthous ulcer (RAU), a common oral immunological disorder that also shows multiple erosive/ulcerative lesions. Whole saliva samples were collected from 20 patients with OLP (erosive E, n = 10 and non-erosive NE, n = 10), 10 patients with RAU (U) and 10 healthy controls (C). DNA was extracted from the saliva samples, and the 16S rDNA gene V4 hypervariable region was analyzed using Illumina sequencing. RESULTS: We obtained 4949 operational taxonomic units (OTUs) from the V4 region in all saliva samples. Community composition analysis showed a clear decreased relative abundance of genera Streptococcus and Sphingomonas in saliva from RAU patients when compared to the other three groups. Relative abundance of Lautropia and Gemella were higher in E group, whereas relative abundance of Haemophilus and Neisseria were higher in NE group when compared to C group. Abiotrophia and Oribacterium were higher in OLP (combining E and NE groups), while Eikenella and Aggregatibacter were lower when compared to C group. There was statistically significance in α-diversity between E and RAU groups(p < 0.05). Significant differences in ß-diversity were detected in bacteria between E and C; NE and C; as well as E and NE groups. The LDA effect size algorithm identified the g_Haemophilus might be the potential biomarker in NE group. CONCLUSIONS: We found that salivary microbiome in erosive OLP was significantly different from that found in RAU; and these changes may be related to the underlying disease process rather than presence of ulcerative/erosive lesions clinically. In addition, our findings in bacterial relative abundance in OLP were significantly different from the previously reported findings, which points to the need for further research in salivary microbiome of OLP.

Updates Regarding Diagnostic Adjuncts for Oral Squamous Cell Carcinoma.

The 5-year survival rate for oral cancer (66%) is still one of the lowest among major human cancers, and delayed diagnosis until an advanced stage is thought to be the main factor contributing to this low survival rate. The detection and diagnosis of oral cancer is currently based on clinical visual examination and histopathological evaluation of a biopsy specimen. In response to the need for early detection of oral cancer, several diagnostic adjuncts have been developed and sold commercially over the years, including vital tissue staining, brush cytology, light-based visualization adjuncts, and the most recently developed test for salivary biomarkers for oral cancer. The purpose of this article is to review the current knowledge and research regarding these diagnostic adjuncts developed for early detection of oral cancer. Clinicians are best served by an awareness of the advantages and disadvantages of each adjunct, and to always consider and correlate with the clinical findings when interpreting the test results from these adjuncts.

Cone-beam computed tomographic imaging of central giant cell granuloma: A comprehensive review.

Purpose: The aim of this study was to characterize the cone-beam computed tomographic (CBCT) imaging features of central giant cell granuloma (CGCG) of the jawbone. Materials and Methods: This study retrospectively reviewed 26 CBCT studies of histologically proven cases of CGCG during a period of 20 years, from 1999 to 2019. Patients' demographic data were recorded, and radiographic features were assessed (location, border, cortication, appearance of the internal structure, locularity, septation, expansion, cortical perforation, effects on surrounding tissue, whether the lesion crossed the midline, and lesion volume). Results: In this study, CGCGs were seen almost twice as often in the mandible than in the maxilla, and 64.7% of mandibular lesions involved the anterior region. Only 26.9% of lesions crossed the midline, a feature that was considered characteristic of CGCG. Furthermore, 65.4% of lesions were unilocular and 34.6% were multilocular. The correlation between a lesion's size and its locularity was statistically significant, and larger lesions showed a multilocular appearance. The mean volume of multilocular lesions was greater than that of unilocular lesions. Conclusion: CGCGs showed variable radiographic features on CBCT, and this imaging modality is highly effective at demonstrating the radiographic spectrum and lesional extent of CGCGs in the jawbone.

Adenomatoid odontogenic tumor: evidence for a mixed odontogenic tumor.

OBJECTIVE: Adenomatoid odontogenic tumor (AOT) was classified by the World Health Organization as a mixed odontogenic tumor in 1992 and reclassified without a clear rationale as an epithelium-only tumor in 2005. The purpose of this study was to investigate if there was any evidence to suggest AOT might be a mixed odontogenic tumor. STUDY DESIGN: Immunohistochemical studies with nestin, dentin sialophosphoprotein (DSPP), cytokeratin, and vimentin were performed using 21 cases of AOT, and the staining results were analyzed according to the various morphologic patterns seen in AOT. Sirius red stain was used to detect the presence of collagen types I and III in AOT products. RESULTS: Our results showed that 20 of 21 (95.23%), 0 of 21 (0%), 21 of 21 (100%), and 20 of 21 (95.23%) cases expressed nestin, DSPP, cytokeratin, and vimentin, respectively. Some cells in rosette/duct-like structures (RDSs) expressed nestin, vimentin, or both, without cytokeratin. Coexpression of vimentin and cytokeratin or of nestin, cytokeratin, and vimentin was noted in some cells. Sirius red staining was positive in eosinophilic products in RDSs, double-layered spheres, and dentinoids. CONCLUSION: Although most AOT cells appear epithelial, there is a small population of cells expressing mesenchymal proteins and secreting collagen types I and III. This evidence suggests that AOT is a mixed odontogenic tumor.

Non-calcifying Langerhans Cell Rich Variant of Calcifying Epithelial Odontogenic Tumor and Amyloid Rich Variant of Central Odontogenic Fibroma: A Unique Entity or a Spectrum?

Overlapping clinicopathological features of non-calcifying Langerhans cell rich variant of calcifying epithelial odontogenic tumor (NCLC-CEOT) and the amyloid rich variant of the central odontogenic fibroma (AR-COF) have been recognized recently. It is still under debate whether these two diseases are indeed one unique disease entity or belong to CEOT and COF, respectively. To clarify this issue, we have performed a literature review to compare the similarities and differences in clinicopathological features among NCLC-CEOT, AR-COF, classic CEOT, and classic COF. We aimed to investigate whether NCLC-CEOT and AR-COF might be the same and one distinctive disease entity, or a variant (or variants) of either CEOT or COF; or whether COF, NCLC-CEOT/AR-COF, and CEOT represented a histopathological spectrum of one disease. Our results indicate that NCLC-CEOT and AR-COF cases share many similar clinicopathological features. Thus, we suggest that they are the same disease entity. Due to nearly no reported recurrence of NCLC-CEOT/AR-COF cases, the conservative surgical treatment is appropriate. The NCLC-CEOT/AR-COF cases show some overlapping clinicopathological features with COF rather than the CEOT cases. However, differences in the clinicopathological features are still recognized among the NCLC-CEOT/AR-COF, COF, and CEOT cases. Future research, particularly molecular biological studies, may further elucidate their relationships and assist proper classification of the NCLC-CEOT/AR-COF cases.

Radiographic manifestations of fibroblastic osteosarcoma: A diagnostic challenge.

Osteosarcoma is the most common primary bone tumor after plasma cell neoplasms. Osteosarcoma has diverse histological features and is characterized by the presence of malignant spindle cells and pluripotent neoplastic mesenchymal cells that produce immature bone, cartilage, and fibrous tissue. Osteosarcoma most frequently develops in the extremities of long bones, but can occur in the jaw in rare cases. The clinical and biological behavior of osteosarcoma of the jaw slightly differs from that of long-bone osteosarcoma. The incidence of jaw osteosarcoma is greater in the third to fourth decades of life, whereas long-bone osteosarcoma mostly occurs in the second decade of life. Osteosarcoma of the jaw has a lower tendency to metastasize and a better prognosis than long-bone osteosarcoma. Radiographically, osteosarcoma can present as a poorly-defined lytic, sclerotic, or mixed-density lesion with periosteal bone reaction response. Multi-detector computed tomography is useful for identifying the extent of bone destruction, as well as soft tissue involvement of the lesion. The current case report presents a fibroblastic osteosarcoma involving the left hemimandible with very unusual radiographic features.

Nanoparticle-based assay for detection of S100P mRNA using surface-enhanced Raman spectroscopy.

The focus of this work is toward the development of a point-of-care (POC) handheld technology for the noninvasive early detection of salivary biomarkers. The initial of focus was the detection and quantification of S100 calcium-binding protein P (S100P) mRNA found in whole saliva for use as a potential biomarker for oral cancer. Specifically, a surface-enhanced Raman spectroscopy (SERS)-based approach and assay were designed, developed, and tested for sensitive and rapid detection of S100P mRNA. Gold nanoparticles (AuNPs) were conjugated with oligonucleotides and malachite green isothiocyanate was then used as a Raman reporter molecule. The hybridization of S100P target to DNA-conjugated AuNPs in sandwich assay format in both free solution and a vertical flow chip (VFC) was confirmed using a handheld SERS system. The detection limit of the SERS-based assay in free solution was determined to be 1.1 nM, whereas on the VFC the detection limit was observed to be 10 nM. SERS-based VFCs were also used to quantify the S100P mRNA from saliva samples of oral cancer patients and a healthy group. The result indicated that the amount of S100P mRNA detected for the oral cancer patients is three times higher than that of a healthy group.

Spindle-cell variant of ameloblastic carcinoma: a report of 3 cases and demonstration of epithelial-mesenchymal transition in tumor progression.

Ameloblastic carcinoma is a rare odontogenic neoplasm that demonstrates the histologic characteristics of ameloblastoma, accompanied by the cytologic features of malignancy. The spindle-cell variant of ameloblastic carcinoma (SCAC) is exceptionally rare, with a total of 10 cases having been reported in the literature to date. Histologically, a prominent sarcomatoid cell population appears to originate from the epithelial (ameloblastic) component. Like conventional ameloblastic carcinoma, most cases of SCAC occur in individuals older than 40 years of age. Here, 3 additional cases of SCAC are reported, 2 of which occurred in young individuals. Diagnostic criteria to aid in the identification of SCAC are proposed. Finally, histologic and immunohistochemical evidence supporting the occurrence of epithelial-mesenchymal transition in SCAC is presented.

Interobserver Variation Among Pathologists in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma.

The aims of this study are as follows: (1) to assess variations among pathologists in evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC), (2) to survey PNI criteria used by pathologists and how they came to adopt those criteria. An electronic survey was sent to 363 oral and/or surgical pathologists. Eligibility criteria included pathology board certification. The survey participants were asked to rate whether PNI was present, absent, or uncertain for 15 provided photomicrographs, which depicted various types of tumor-nerve relationships without excessive desmoplasia or lymphocytic host response. The survey obtained information regarding demographics, whether PNI criteria were taught during residency, criteria used by participants to evaluate PNI, how the participants developed their criteria, and agreement with six proposed PNI definitions. 88 pathologists completed the survey. The participants included 47 males and 41 females, with average age = 49 years and average practice experience = 17 years. Practice settings included dental school (40 %), medical school (36 %), private pathology lab (13 %), and other (11 %). Agreement between participants in rating PNI status for the provided images was fair (κ = .38, 95 % CI .37-.39). 56 % of respondents indicated that they were taught PNI criteria during residency training. The basis for criteria currently used by participants included residency training (n = 42), published literature (n = 29), and own experience/views (n = 32). Agreement regarding six proposed PNI definitions was slight (κ = .10, 95 % CI .08-.11). In conclusion, interobserver agreement in assessing PNI status was fair. Our results suggest that more widely accepted, objective, and reproducible criteria are needed for evaluating PNI in OSCC.

Phosphaturic Mesenchymal Tumor: 2 New Oral Cases and Review of 53 Cases in the Head and Neck.

Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm that secretes fibroblast growth factor-23 (FGF-23) and causes oncogenic osteomalacia. It occurs in adults with equal gender distribution and the most common location is the lower extremities, followed by the head and neck. Besides osteomalacia, the clinical presentation includes bone pain and multiple bone fractures. Microscopic features consist of spindle cells, multinucleated giant cells, and calcifications embedded in a chondromyxoid matrix. Laboratory findings indicate normal calcium and parathyroid levels, hypophosphatemia, and increased levels of FGF-23 that usually revert to normal after surgical removal. Due to its rarity, the purpose of the study was to report 2 new oral cases of PMT and to review the literature in the head and neck. The first case occurred in the gingiva and had been present for 6 years. The second case was a recurrence of a previously diagnosed PMT in the right mandible that metastasized to the lung and soft tissue. The literature review included 53 cases in the head and neck. There was a predilection for extra-oral sites (76%) compared to intra-oral sites (24%) with paranasal sinuses considered the most common location (38%) followed by the mandible (15%). There were 9 recurrences that included 3 malignant cases indicating a potentially aggressive tumor. Due to the indeterminate biological behavior of PMT and its rarity, a comprehensive evaluation of medical, laboratory, radiographic, and histological findings are crucial for a definitive diagnosis and treatment.

A novel multimodal optical imaging system for early detection of oral cancer.

OBJECTIVES: Several imaging techniques have been advocated as clinical adjuncts to improve identification of suspicious oral lesions. However, these have not yet shown superior sensitivity or specificity over conventional oral examination techniques. We developed a multimodal, multi-scale optical imaging system that combines macroscopic biochemical imaging of fluorescence lifetime imaging with subcellular morphologic imaging of reflectance confocal microscopy for early detection of oral cancer. We tested our system on excised human oral tissues. STUDY DESIGN: In total, 4 tissue specimens were imaged. These specimens were diagnosed as either clinically normal, oral lichen planus, gingival hyperplasia, or superficially invasive squamous cell carcinoma. The optical and fluorescence lifetime properties of each specimen were recorded. RESULTS: Both quantitative and qualitative differences among normal, benign, and squamous cell carcinoma lesions can be resolved with fluorescence lifetime imaging reflectance confocal microscopy. The results demonstrate that an integrated approach based on these two methods can potentially enable rapid screening and evaluation of large areas of oral epithelial tissue. CONCLUSIONS: Early results from ongoing studies of imaging human oral cavity illustrate the synergistic combination of the 2 modalities. An adjunct device based on such optical characterization of oral mucosa can potentially be used to detect oral carcinogenesis in early stages.

Inactivation of Fam20B in Joint Cartilage Leads to Chondrosarcoma and Postnatal Ossification Defects.

During endochondral ossification, chondrocytes embed themselves in a proteoglycan-rich matrix during the proliferation-maturation transition. Accumulating evidence shows that proteoglycans are essential components for chondrocyte proliferation and differentiation. When we conditionally inactivated FAM20B (Family with sequence similarity 20 member-B), which is a newly identified xylose kinase essential for glycosaminoglycan (GAG) formation on the protein core of proteoglycans, from the dental mesenchyme using Osr2-Cre, which is also strongly expressed in joint cartilage, we found chondrosarcoma in the knee joint and remarkable defects of postnatal ossification in the long bones. Mechanistic analysis revealed that the defects were associated with gain of function in multiple signaling pathways in the epiphyseal chondrocytes, such as those derived by WNT, BMP, and PTHrP/IHH molecules, suggesting that the FAM20B-catalyzed proteoglycans are critical mediators for a signaling balance in the regulatory network controlling chondrocyte differentiation and proliferation. In particular, we demonstrated that the WNT inhibitor was able to rescue part of the bone defects in Osr2-Cre;Fam20B(fl/fl) mice, indicating that FAM20B-catalyzed proteoglycans regulate postnatal endochondral ossification partially through the mediation of WNT signaling.

Multiple orthokeratinized odontogenic cysts: a case report.

The purpose of this report is to document the clinical, radiographic, pathological and molecular findings of the first case of multiple orthokeratinized odontogenic cysts (OOCs). Multiple odontogenic keratocysts are one of the major features of nevoid basal cell carcinoma syndrome (NBCCS), and loss of heterozygosity in the PTCH gene, the culprit gene for NBCCS, has recently been found in sporadic OOC cases. Therefore, in this presenting case, we also investigated the possibility that this patient might also have NBCCS, by comparing the available clinical information and the molecular findings of this case to the diagnostic criteria for NBCCS (as proposed by the First International Colloquium on NBCCS in 2011). However, this patient with multiple OOCs showed no evidence of having NBCCS. This conclusion supports the findings from previous case series based on sporadic cases that OOC does not appear to be associated with NBCCS.

Osteosarcoma arising in Paget's disease of the mandible.

Although osteosarcoma is a well-known complication of Paget's disease of bone, it uncommonly develops in the jaw bones. We present an osteosarcoma arising in Paget's disease of the mandible with unique features of a normal serum alkaline phosphatase level, and histologic features of telangiectatic change in the osteosarcoma and association with cemento-osseous dysplasia. Sixteen reported cases of osteosarcoma arising in Paget's disease of the jaw bones (OPJ) are also reviewed and compared to osteosarcoma arising in Paget's disease occurring in the entire skeleton (OPS) and osteosarcoma arising de novo in the jaw bones (OJ). Females are more commonly involved in OPJ in contrast to a male predominance in OPS and OJ. OPJ also has a distinctively higher percentage involving blacks compared to OPS. The prognosis of OPJ is poor, with 69% of patients dying within two years after diagnosis. Early recognition, early and aggressive treatment are important to improve the prognosis and are hence emphasized.

Calcifying epithelial odontogenic tumor showing microscopic features of potential malignant behavior.

Calcifying epithelial odontogenic tumor (CEOT) is a rare benign, but locally aggressive, odontogenic tumor, and only 2 cases of malignant CEOT are reported in the literature. We describe a case of an atypical CEOT that penetrates the blood vessels, invades bone, and perforates the cortical plates of the mandible. On histologic examination, it shows marked pleomorphism and numerous mitotic figures, including a tripolar mitotic figure. Proliferating activity was found to be 5 times higher than typical CEOTs as demonstrated by the proliferating index, Ki-67, and analyzed by a computerized image analysis system. The Ki-67 labeling index of this case was also compared to various previously reported benign and malignant neoplasms. Although there is no clinical finding of metastasis, we believe this neoplasm has malignant potential on the basis of the histologic features of vascular invasion, significant mitotic activity, atypical mitotic figures, and an increased proliferating index.