Clinicopathological evaluation of oral leukoplakia: a single-center study of 676 cases in Japan.

OBJECTIVES: To analyze the clinical and histopathological characteristics of oral leukoplakia (OL) in the Japanese population and investigate the prevalence and risk factors for epithelial dysplasia (ED) and carcinoma within lesions. STUDY DESIGN: Data, including age, sex, lesion site, and histopathological features, of 676 cases diagnosed with OL over the previous 10 years were analyzed. Dysplasia and carcinoma prevalence were determined. RESULTS: In male patients, the most affected site was the gingiva (42.7%), whereas in females, it was the tongue (47.6%). Moreover, ED was more prevalent in males (41.9%), whereas epithelial hyperplasia was more common in females (44.7%). A significant difference was observed between affected sites with regard to the presence of dysplasia. The ED rates by site were 64.6% and 33.7% for the tongue and gingiva, respectively (P < 0.05). The squamous cell carcinoma rates by site were 23.4%, 5.4%, and 3.4% for the tongue, buccal mucosa, and gingiva, respectively (P < 0.05). Logistic regression analysis revealed a higher prevalence of dysplasia in males than it did in females and that the risk for both dysplasia and carcinoma was highest in the tongue. CONCLUSIONS: Dysplasia is common in OL cases, often showing carcinoma. Early biopsy and interventions are key in OL management.

The Effects of Tricalcium-Silicate-Nanoparticle-Containing Cement: In Vitro and In Vivo Studies.

A tricalcium-silicate-nanoparticle-containing cement (Biodentine) was developed to overcome the disadvantages of existing mineral trioxide aggregate (MTA) dental materials. This study aimed at evaluating the effects of Biodentine on the osteogenic differentiation of human periodontal ligament fibroblasts (HPLFs) in vitro and the healing of furcal perforations created experimentally in rat molars in vivo, in comparison to MTA. The in vitro studies performed the following assays: pH measurement using a pH meter, the release of calcium ions using a calcium assay kit, cell attachment and morphology using SEM, cell proliferation using a coulter counter, marker expression using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and cell mineralized deposit formation using Alizarin Red S (ARS) staining. In the in vivo studies, MTA and Biodentine were used to fill the rat molar perforations. Rat molars were processed at 7, 14 and 28 days for analysis of inflammatory processes using hematoxylin and eosin (HE) staining, immunohistochemical staining of Runx2 and tartrate-resistant acid phosphate (TRAP) staining. The results demonstrate that the nanoparticle size distribution of Biodentine is critical for osteogenic potential at an earlier stage compared to MTA. Further studies are required to elucidate the mechanism of action of Biodentine in osteogenic differentiation.

Intraoral Minor Salivary Gland Tumors: A Retrospective, Clinicopathologic, Single-Center Study of 432 Cases in Japan and a Comparison with Epidemiological Data.

BACKGROUND: Intraoral minor salivary gland tumors are relatively rare lesions with histological subtypes not commonly found in major salivary glands. This study aimed to retrospectively evaluate the clinicopathologic features of intraoral minor salivary gland tumors from the Tokyo Dental College Hospital, Japan, and compare them with findings from other epidemiological studies. METHODS: We conducted a retrospective clinicopathologic evaluation of 432 cases of intraoral minor salivary gland tumors [161 male (37.3%) and 271 female (62.7%) patients; mean age: 52.5 and 48.6 years for males and females, respectively; age at diagnosis: 7-87 (mean: 50.1) years] from the Tokyo Dental College Hospital between 1975 and 2022, including 283 benign tumors (65.5%) and 149 malignant tumors (34.5%). RESULTS: The most common benign tumor was pleomorphic adenoma (n = 239), whereas mucoepidermoid carcinoma was the most common malignant tumor (n = 74). The mean age of patients with benign and malignant tumors was 48.4 and 53.2 years, respectively, with patients with malignant tumors being significantly older (P = 0.0042). The mean age of patients with malignant tumors was significantly higher in males (56.7 years) than in females (50.9 years) (P = 0.0376), although the mean age of patients with benign tumors did not differ by sex. Tumors were commonly located in the palate [250 cases (57.9%)]. Benign tumors were more frequent in the palate, upper lip, and buccal mucosa, whereas malignant tumors were more frequent in the palate, floor of the mouth, buccal mucosa, and retromolar area. CONCLUSIONS: Understanding the features of intraoral minor salivary gland tumors is useful for diagnosis. Our study provides important epidemiological data (patient differences in age at occurrence, sex, and site of origin) that will inform clinicians and researchers.

Evaluation of oral brush liquid-based cytology for oral squamous cell carcinoma: a comparative study of cytological and histological diagnoses at a single center.

PURPOSE: Liquid-based cytology is highly useful in oral cytology. However, there are only few reports on the accuracy of this method. The current study aimed to compare oral liquid-based cytological and histological diagnoses and to evaluate items that should be considered in oral cytological diagnosis for oral squamous cell carcinoma. METHODS: We included 653 patients who underwent both oral cytological and histological examinations. Data on sex, specimen collection region, cytological and histological diagnoses, and histological images were reviewed. RESULTS: The overall male-to-female ratio was 1:1.18. The tongue was the most common specimen collection region, followed by the gingiva and buccal mucosa. The most common cytological examination result was negative (66.8%), followed by doubtful (22.7%) and positive (10.3%). The sensitivity, specificity, positive predictive value, and negative predictive value of cytological diagnosis were 69%, 75%, 38%, and 92%, respectively. Approximately 8.3% of patients with a negative cytological diagnosis had a histological diagnosis of oral squamous cell carcinoma. Furthermore, 86.1% of histopathologic images of cytology-negative squamous cell carcinomas exhibited well-differentiated keratinocytes lacking atypia on the surface. The remaining patients developed recurrence, or they had low cell counts. CONCLUSION: Liquid-based cytology is useful in screening oral cancer. However, a cytological diagnosis of superficial-differentiated oral squamous cell carcinoma is occasionally inconsistent with the histological diagnosis. Therefore, histological and cytological examinations should be performed if tumor-like lesions are suspected clinically.

Second Primary Metachronous Malignancies Occurring in Oral Cavity of Young Adult-A Case Report.

The incidence of oral cancer in Japan is increasing. Interestingly, the number of young patients with oral cancer is also rising. A 19-year-old man with no history of smoking or drinking alcohol presented with a 20×15-mm elastic, hard, protruding mass with a white surface on the right-hand margin of the tongue. A biopsy resulted in a diagnosis of a well-differentiated squamous cell carcinoma of the tongue, for which a partial resection was subsequently performed. During regular follow-up, the patient demonstrated no clinical or imaging abnormalities until 4 years and 9 months later, when erosion was observed at the right palatoglossal arch. A malignant tumor of the right palatoglossal arch was diagnosed based on cytology and imaging findings, and total resection of the lesion performed. Histopathological examination of the resected lesion revealed a moderately differentiated squamous cell carcinoma. Epithelial dysplasia on the right-hand margin of the tongue was diagnosed 4 years and 9 months after the second surgery and was subsequently resected. The patient's condition has been favorable for 7 years since the diagnosis of the second cancer, with no noted recurrence. This case emphasizes the importance of follow-up after initial treatment, as even young people, who are likely to have to endure long-lasting consequences from treatment, can develop metachronous cancer in the oral cavity.

Genetic Study of BRAF V600E and SMO L412F Mutations in Japanese Patients with Ameloblastoma.

Background and aim. Ameloblastoma is a benign, intraosseous, progressively growing, epithelial, odontogenic neoplasm. BRAF and SMO mutations have been reported in ameloblastoma. In this study, we evaluated BRAF V600E and SMO L412F mutations; and assessed the relationship between BRAF V600E mutant expression and the clinicopathological features in Japanese patients with ameloblastoma. Methods. We examined 24 formalin-fixed paraffin-embedded samples. All specimens were from patients with mandibular ameloblastoma: 20 were conventional ameloblastoma and 4 were unicystic ameloblastoma. The BRAF V600E mutation was assessed by Sanger sequencing and immunohistochemistry, and the SMO L412F mutation was assessed only by Sanger sequencing. Results. Twenty of the 24 (83%) ameloblastoma samples carried the BRAF V600E mutation; 22 of the 24 (92%) samples were immunohistochemically positive for BRAF V600E. However, the SMO L412F mutation was not detected in any of them. The BRAF V600E mutation status did not correlate with the clinicopathological features, such as age, sex, location, method, recurrence, and subtype. Conclusion. BRAF inhibitors could be a potential treatment option for Japanese patients with ameloblastoma, harboring the BRAF V600E mutation.

Frequency of Odontogenic Tumors: A Single Center Study of 1089 Cases in Japan and Literature Review.

Several attempts have been made to classify odontogenic tumors; however, the need for a uniform international classification system led the World Health Organization (WHO) to present a classification of odontogenic tumors in 1971. We aimed to evaluate the number and types of odontogenic tumors examined at the Tokyo Dental College Hospital in Japan to determine the frequency and types of odontogenic tumors, based on the 2017 WHO classification system, as this information has not been reported previously in Japan. We also compared the results of our evaluation with those reported in previous studies. We conducted a clinicopathological evaluation of odontogenic tumors examined at the Tokyo Dental College Hospital between 1975 and 2020. This included an analysis of 1089 cases (malignant, n = 10, 0.9%; benign, n = 1079, 99.1%) based on the 2017 World Health Organization Classification of Head and Neck Tumors. We identified 483 (44.3%), 487 (44.7%), and 109 (10.0%) benign epithelial odontogenic, mixed odontogenic, and mesenchymal tumors, respectively. The most common tumor types were odontoma (42.5%) and ameloblastoma (41.9%). Of the 1089 cases, 585 (53.7%) and 504 (46.3%) were male and female patients, respectively. Ameloblastoma and ameloblastic fibroma occurred more commonly in male patients, whereas odontogenic fibroma and cemento-ossifying fibroma affected female patients primarily. The age at diagnosis ranged from three to 87 (mean, 29.05) years. In 319 (29.3%) patients, the age at diagnosis ranged from 10 to 19 years. Ameloblastoma and odontoma were the most common tumor types among patients in their 20s and those aged 10-19 years, respectively. In 737 (67.7%) and 726 (66.7%) patients, the tumors were located in the mandible and posterior region, respectively. Ameloblastoma was particularly prevalent in the posterior mandible. Odontogenic tumors are rare lesions and appear to show a definite geographic variation.

Effects of Excimer Laser Treatment of Zirconia Disks on the Adhesion of L929 Fibroblasts.

The adhesion of zirconia and soft tissue is very important for the success of zirconia implants. The aim of this study was to characterize the effects of excimer laser treatment of zirconia on the adhesion of L929 fibroblasts. In this study, polished zirconia disks treated with an excimer laser were the experimental group and untreated zirconia disks were the control group. Surface roughness and contact angles of zirconia disks were measured. mRNA expression levels of integrin ß1 and collagen type I α1 in L929 fibroblasts cultured on zirconia disks were measured using qRT-PCR. Cell morphology was evaluated using 3D laser microscopy and the expression of vinculin was characterized using confocal microscopy. There was no significant difference in the surface roughness of zirconia disks, but contact angles were significantly lower. mRNA expression of integrin ß1 was significantly higher at 3, 6 and 24 h and of collagen type I α1 was significantly higher at 6 and 24 h. L929 fibroblasts tended to form elongated microspikes and vinculin colocalization in those microspikes. Furthermore, vinculin was strongly expressed in filopodia of L929 fibroblasts at 24 h. These results suggest that excimer laser treatment improves adhesion between zirconia disks and L929 fibroblasts.

The effect of fibroblast growth factor 7 on human dental pulp stem cells for differentiation to AQP5-positive and αSMA-positive cells in vitro and in vivo.

OBJECTIVES: Transplantation of stem cells into wounds has become popular in regeneration therapies. As stem cells for transplantation, human dental pulp stem cells (hDPSCs) are known to be pluripotent cells that are relatively easy to collect from the pulp of deciduous or wisdom teeth. The purpose of this study was to investigate whether hDPSCs treated with fibroblast growth factor 7 (FGF7) would contribute to the regeneration of wounded rat submandibular glands (SMGs). MATERIALS AND METHODS: In in vitro studies, hDPSCs were treated with or without FGF7 and mRNA expression levels were examined at days 3, 7 and 14 using qRT-PCR. The target genes analyzed were BMI1 as an undifferentiated marker, AQP5 as an acinar cell marker, CK19 as a ductal epithelial cell marker, αSMA as a myoepithelial cell marker and VIMENTIN as a fibroblast marker. In in vivo studies, hDPSCs treated with or without FGF7 for 14 days were mixed with type I collagen gels and were transplanted into wounded rat SMGs. Hematoxylin-Eosin and immunohistochemical staining were performed at days 3 and 7, and the numbers of positive cells were counted. The primary antibodies used were against BMI1, AQP5, αSMA, PanCK and VIMENTIN. RESULTS: In the in vitro studies, mRNA levels of BMI1 were decreased and αSMA were increased at days 3, 7 and 14, while AQP5 was increased at day 14 in the FGF7 group. In the in vivo studies, the proliferation of hDPSCs and cell islands was observed at day 7 in the FGF7 group. Few BMI1-positive cells were observed, while numbers of AQP5-positive and αSMA-positive cells were increased at days 3 and 7 in the FGF7 group. Moreover, cell islands were AQP5-positive. CONCLUSION: These results suggest that FGF7-treated hDPSCs differentiate into AQP5-positive and αSMA-positive cells. Moreover, AQP5-positive cell aggregations were formed.

Current status of dental metal allergy in Japan.

PURPOSE: To assess the current status of patients with dental metal allergies in Japan. METHODS: This study analyzed dental metal allergy in 1225 patients (1:3 male to female ratio; average age 53.0 ±16.5 years), including 300 who were scheduled to undergo dental implant surgery, between 2006 and 2016. For diagnosis of metal allergy, patch tests using metal allergens were performed. Additionally, when necessary, metal element analysis of dental alloys was performed in the mouths of some patients using an X-ray fluorescence analyzer for those who exhibited positive reactions. RESULTS: Among 925 patients (i.e., excluding those scheduled to undergo dental implant surgery [n=300]), nearly one-half (44.0%) exhibited a positive response to any metal element in the patch test. The positivity rates were as follows: nickel (22.5%); palladium (14.8%); and zinc (11.5%). Almost one-half (42.3%) of the patients had diseases associated with metal allergy. Among patients who exhibited a positive reaction to any metal element in the patch test, more than two-thirds (67.9%) had dental alloys containing the positive metal element(s). One-half (55.6%) of the patients who underwent treatment to remove the metal experienced improvement in symptoms. In patients who underwent patch testing as an implant preoperative examination, several (2.7%) exhibited a positive reaction to titanium. CONCLUSIONS: Dental metals, including nickel, palladium and zinc, which are indispensable to dental treatment in Japan, had high positivity rates in patch testing, and one-half of the patients improved following removal of the metal. Additionally, there were several patients with allergy to titanium.

Congenital Epulis: A Case and Review of the Literature.

Congenital epulis is an unusual benign oral mucosal lesion in newborns with no tendency to recur after excision. The histogenesis of the lesion is unknown, but it is believed to be of mesenchymal origin. We describe a case of congenital epulis (20×10 mm) in the mandibular gingiva of a newborn. The mass, which was smooth-surfaced and pedunculated with a healthy color, was surgically removed at 5 months post-birth. Histologically, the tumor consisted mainly of large eosinophilic granular cells. Immunohistochemical studies revealed intense staining for vimentin, STRO-1, and CD44, suggesting that it was derived from mesenchymal cells. The literature and immunohistochemical profile of congenital epulis are also discussed.