Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

Clinical, histopathological characteristics and malignant transformation of proliferative verrucous leukoplakia with 36 patients: a retrospective longitudinal study.

BACKGROUND: Proliferative verrucous leukoplakia (PVL), distinguished by its malignant transformation rate of 43.87% to 65.8%, stands as the oral potentially malignant disorder with the highest propensity for malignancy. PVL is marked by distinctive heterogeneity regarding the clinical or histopathological characteristics as well as prognostic factors pertinent to this condition. The purpose of this study is to compile and assess the clinicopathological features, malignant transformation, and associated risk factors in patients diagnosed with PVL. METHODS: This study is a hospital-based retrospective longitudinal study of 36 patients diagnosed with PVL from 2013 to 2023. We conducted complete clinical and histopathological evaluations of the patients. RESULTS: The cohort comprised 16 males and 20 females, yielding a male-to-female ratio of 1:1.25. The follow-up period ranged from 8 to 125 months, with an average of 47.50 months. The most common clinical type of lesion was the verrucous form (58.33%), and the gingiva was the most common site (44.44%). Each patient had between 2 to 7 lesions, averaging 3.36 per patient. During the follow-up period, twelve patients (33.3%) developed oral cancer, with an average time to malignant transformation of 35.75 months. Kaplan-Meier survival analysis indicated that patients with complaints of pain, roughness, or a rough sensation, with diabetes, and the presence of cytologic atypia histologically showed a higher risk of malignant transformation (p < 0.05). In this study, the rate of malignant transformation in the treatment group (5/23) was lower than that in the untreated group (7/13), however, no statistically significant difference (p = 0.05). CONCLUSION: The main complaints of pain, roughness, or foreign body sensation, coupled with cytologic atypia histologically are indicative of an increased risk of malignant transformation in PVL. Further research is needed to elucidate the influence of these clinicopathological parameters on the malignant progression of PVL.

Comparison of the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible, chronic suppurative osteomyelitis, and craniofacial fibrous dysplasia.

BACKGROUND: There are relatively few reports on the histopathological characteristics of diffuse sclerosing osteomyelitis of the mandible (DSOM), which is difficult to distinguish from chronic suppurative osteomyelitis (CSO) and craniofacial fibrous dysplasia (CFD). This study aimed to summarize and compare the histopathological characteristics of DSOM, CFD, and CSO. MATERIALS AND METHODS: In this study, hematoxylin and eosin-stained sections of patients with DSOM, CSO, and CFD at the Peking University Hospital of Stomatology from 2015 to 2020 were retrieved. The histopathological characteristics were summarized, including new bone formation, inflammatory cell infiltration, bone trabecular morphology, osteoclasts, sequestrum, bacterial mass, and calcified spherules, similar to cementicles. The histopathological characteristics of DSOM, CSO, and CFD were compared, and the results were statistically analyzed. RESULTS: In total, 50, 13, and 10 patients with DSOM, CSO, and CFD were included in this study, respectively. In terms of new bone formation, both DSOM and CSO showed reactive bone formation (p = 1), whereas CFD mainly showed fiber osteogenesis (p < 0.001). The inflammatory cells of DSOM were mainly lymphocytes and plasma cells, whereas those of CSO were mainly lymphocytes and neutrophils (p < 0.001), and there was usually no inflammatory cell infiltration in the CFD specimens (p < 0.001). DSOM, CSO, and CFD showed irregular bone trabeculae (p = 0.045, p = 0.703) and active osteoclasts (p1 = 0.189, p2 = 0.256). DSOM showed a small amount of bacterial mass but no sequestrum; neither of which was found in CFD (p = 1, p = 1), but it was common in CSO (p = 0.011 and p = 0.025). DSOM and CSO showed smooth and regular basophilic lines (p = 0.308), whereas CFD showed a rough and irregular basophilic line (p < 0.001). CONCLUSIONS: The histopathological characteristics of the three diseases were partly similar, but there were evident differences. The main differences are the type of new bone formation, types and distribution of inflammatory cells, and presence of sequestrum and bacterial masses. These differences will help clinicians diagnose DSOM.

PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.

BACKGROUND: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC-0449 and GANT61 on OKC fibroblasts. METHODS: Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS-related fibroblasts were cultured in vitro. The effect of PTCH1 non-truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound-healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co-culture. Quantitative real-time PCR detected the effects of GDC-0449 or GANT61 on the SHH signaling pathway in NBCCS-related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and/or SMO c.2081C>G (p.P694R) mutations. RESULTS: PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS-related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC-0449 significantly inhibited the SHH signaling pathway in NBCCS-related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS-related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC-0449 but inhibited by GANT61. CONCLUSIONS: Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC-0449 could be used to treat OKCs, especially NBCCS-related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC-0449; however, GANT61 may be used as an alternative inhibitor.

[Application of Deep Learning in Differential Diagnosis of Ameloblastoma and Odontogenic Keratocyst Based on Panoramic Radiographs].

Objective To evaluate the accuracy of different convolutional neural networks (CNN),representative deep learning models,in the differential diagnosis of ameloblastoma and odontogenic keratocyst,and subsequently compare the diagnosis results between models and oral radiologists. Methods A total of 1000 digital panoramic radiographs were retrospectively collected from the patients with ameloblastoma (500 radiographs) or odontogenic keratocyst (500 radiographs) in the Department of Oral and Maxillofacial Radiology,Peking University School of Stomatology.Eight CNN including ResNet (18,50,101),VGG (16,19),and EfficientNet (b1,b3,b5) were selected to distinguish ameloblastoma from odontogenic keratocyst.Transfer learning was employed to train 800 panoramic radiographs in the training set through 5-fold cross validation,and 200 panoramic radiographs in the test set were used for differential diagnosis.Chi square test was performed for comparing the performance among different CNN.Furthermore,7 oral radiologists (including 2 seniors and 5 juniors) made a diagnosis on the 200 panoramic radiographs in the test set,and the diagnosis results were compared between CNN and oral radiologists. Results The eight neural network models showed the diagnostic accuracy ranging from 82.50% to 87.50%,of which EfficientNet b1 had the highest accuracy of 87.50%.There was no significant difference in the diagnostic accuracy among the CNN models (P=0.998,P=0.905).The average diagnostic accuracy of oral radiologists was (70.30±5.48)%,and there was no statistical difference in the accuracy between senior and junior oral radiologists (P=0.883).The diagnostic accuracy of CNN models was higher than that of oral radiologists (P<0.001). Conclusion Deep learning CNN can realize accurate differential diagnosis between ameloblastoma and odontogenic keratocyst with panoramic radiographs,with higher diagnostic accuracy than oral radiologists.

GNAS mutation analysis assists in differentiating chronic diffuse sclerosing osteomyelitis from fibrous dysplasia in the jaw.

Chronic diffuse sclerosing osteomyelitis of the mandible (DSOM) and fibrous dysplasia (FD) are distinct lesions with overlapping clinicopathological features that complicate their diagnosis. This study aimed to evaluate the efficacy of GNAS mutation analysis in differentiating between these two conditions. DNA samples from patients with DSOM (n = 35) and FD (n = 29) were collected to analyze the presence of GNAS mutations in exons 8 and 9, the two previously reported hotspot regions, using polymerase chain reaction and direct sequencing. Twenty-four of 29 patients (83%) with FD showed missense mutations in codon 201 in exon 8, whereas no mutation was detected in exon 9. No mutations were found in any of the 35 cases with DSOM. We also identified one case with an uncertain diagnosis due to overlapping clinicopathological features of DSOM and FD. A Q227H mutation was detected in this case, that confirmed the diagnosis of FD. Taken together, the findings indicate that mutational analysis of the GNAS is a reliable approach to differentiate between DSOM and FD of the jaw.

Orthokeratinized odontogenic cysts: A clinicopathologic study of 159 cases and molecular evidence for the absence of PTCH1 mutations.

BACKGROUND: Orthokeratinized odontogenic cyst (OOC), a newly designated entity of odontogenic cysts, is an intraosseous jaw cyst that is entirely or predominantly lined by orthokeratinized squamous epithelium. The aim of this study was to report a large series of OOC to substantiate its clinicopathologic profiles and to investigate PTCH1 mutations in OOCs. METHOD: The clinicopathologic features of 167 OOCs from 159 patients were analyzed and the immunohistochemical expression of markers related to cell differentiation and proliferation was evaluated. Furthermore, PTCH1 mutations were analyzed in 14 fresh samples of OOC. RESULTS: OOCs occurred mostly in the third and fourth decades (60.4%) with a male predilection (66.7%). The lesions developed more often in the mandible than maxilla, primarily in the posterior mandible and ramus. Eight patients (5.0%) showed multiple locations of either bilateral posterior mandible (n = 6) or both the maxilla and mandible. Radiographically, the majority of OOCs (91.2%) showed a well-demarcated, unilocular radiolucency with 14 multilocular cases (8.8%). A follow-up of 131 patients (123 treated by enucleation with or without marsupialization and eight by peripheral ostectomy) revealed no recurrence during an average period of 4.56 years after surgery. Immunohistochemistry indicated lower proliferative activity and a varying epithelial differentiation pattern in OOC compared with odontogenic keratocysts (OKC). No PTCH1 mutation was detected, except for three known single nucleotide polymorphisms. CONCLUSION: The clinicopathological and molecular differences between OOC and OKC justified their separation, and unlike OKCs, OOCs did not harbor PTCH1 mutations, suggesting different pathogenesis underlying these two jaw cysts.

Biopsied non-dental plaque-induced gingival diseases in a Chinese population: a single-institute retrospective study.

BACKGROUND: While inflammatory diseases such as gingivitis and periodontitis induced by dental plaque biofilms constitute the majority of gingival lesions, gingiva can also be affected by a variety of diseases with aetiologies different from bacterial biofilms. The aim of this study was to retrospectively analyze the frequency and distribution of non-dental plaque-induced gingival diseases (NDPIGDs) in the Chinese population in a single institute. METHODS: A total of 6859 samples of biopsied gingival diseases during the period 2000-2019 were obtained from the Department of Pathology, Peking University Hospital of Stomatology. Lesions were categorized by histopathological diagnosis, pathological characteristics and the new classification of gingival health and gingival diseases/conditions. Demographic information, such as gender, location, and age, were also analyzed. RESULTS: Among 6859 biopsied NDPIGD samples, the five most frequent diagnoses included oral squamous cell carcinoma (OSCC, n = 2094), fibrous hyperplasia (n = 2026), pyogenic granuloma (n = 478), epithelial dysplasia (n = 477), and epithelial hyperplasia/hyperkeratosis (n = 436). All types could be grouped into nine categories according to their pathological characteristics. The most common biopsied NDPIGDs category was "hyperplastic lesions" (n = 2648, 38.61%), followed by "malignant neoplasms" (n = 2275, 33.17%). The most common diagnosis types in each category were fibrous hyperplasia and OSCC. Of all NDPIGDs, most lesions could be categorized into the new classification of gingival health and gingival diseases/conditions; only 7.07% did not fit the current classification system. CONCLUSIONS: The present study is the first report on the frequency and distribution of biopsied NDPIGDs in a Chinese population. Unlike previous studies, the most prevalent categories were "hyperplastic lesions" and "malignant neoplasms". The proportion of "malignant neoplasms" and "oral potentially malignant disorders" was remarkably higher than in previous researches. Nevertheless, the study provided epidemiological information on many NDPIGDs, which could be useful for future health policies as well as screening programs.

Development and validation of nomogram for prediction of malignant transformation in oral leukoplakia: A large-scale cohort study.

PURPOSE: Oral leukoplakia (OL) is the well-known disorder of oral mucosa, which has potential to be malignant and can lead to squamous cell carcinoma (OSCC). In the following study, we developed a comprehensive nomogram for predicting the malignant progression of OL, based on analysis of clinicopathological variables. METHODS: A retrospective analysis of patients diagnosed with OL was performed between 1998 and 2017 at the Peking University School and Hospital of Stomatology. OL was confirmed by pre-treatment biopsy. The candidate risk factors for OL malignant transformation were screened from clinicopathological variables using the Cox proportional hazard regression analysis. The nomogram model was generated based on the COX regression results and was validated through Harrell concordance index (c-index) and calibration plots RESULTS: The incidence of OL malignant transformation (MT) was 12.2% (107/875), and the mean follow-up time was 4.5 years. The risk factors (age, histologic grade, site of lesion and smoking habit) derived from Cox proportional hazard regression analysis were incorporated in a novel nomogram model for prediction of MT severity. The c-index value of the nomogram model was 0.752, which confirmed the prediction ability; and was further confirmed by calibration plots results. CONCLUSION: Our data suggest that patients with OL who are over 50 years old, non-smokers with dysplasia, and OL lesions involving the lip, the floor of mouth, and tongue have an enhanced risk of MT. The established nomogram model has the predictive value of malignant progression, which is conductive to screen high-risk patients and guide treatment strategy.

High-Performance Polymer Solar Cells Achieved by Introducing Side-Chain Heteroatom on Small-Molecule Electron Acceptor.

Side chains of photovoltaic materials play an important role in determining charge transport property, film morphology, and the corresponding device performance. In this work, two new acceptor materials, ATT-6 and ATT-7 with different side chains, m-hexylphenyl and m-hexyloxyphenyl on the indacenodithiophene, are designed and synthesized for applications in non-fullerene polymer solar cells. ATT-7 shows a higher absorption coefficient, increased crystallinity, and improved electron mobility in comparison with ATT-6. Using wide-bandgap polymer poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)-benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2-ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione)] (PBDB-T) as donor, optimized devices based on PBDB-T:ATT-7 and PBDB-T:ATT-6 delivers power conversion efficiencies of 10.30% and 8.39%, respectively. The higher performance of ATT-7-based device can be attributed to efficient exciton dissociation, reduced bimolecular recombination, and enhanced and balanced charge carrier mobilities. These results indicate that side-chain modification is an easy but efficient way in the design of high-performance non-fullerene acceptors.

Clinicopathologic study on a rare variant of ameloblastoma with basal cell features.

OBJECTIVES: To investigate the clinical features, pathologic manifestations, and biologic behaviors of a variant of ameloblastoma with basal cell features (AM-BC). MATERIALS AND METHODS: Following retrospective review of the clinical and pathological data of six cases of AM-BC, we described their histological and immunohistochemical (IHC) features and discussed the biologic behaviors, prognoses, pathogenesis, and clinical relevance of AM-BC. Direct sequencing of polymerase chain reaction products was also performed in all cases. RESULTS: The six cases of AM-BC involved four women and two men, aged 22-82 years. Four lesions occurred in the maxilla and two in the mandible. Histologically, the basal cells tended to be arranged as unequally sized follicles, strands, or cords of odontogenic epithelium in the connective tissue stroma. Little or no stellate reticulum was present in the central portion of the nest. Expression of CKs was consistent with other histological variants of ameloblastoma (AM), but AM-BC had significantly higher p53 and Ki-67 (p < 0.05) labeling indices than other histological variants of AM. Two patients had BRAF gene mutations. CONCLUSION: Ameloblastoma with basal cell features is a very rare variant of AM. Our study showed the differences and relationships that exist between AM-BC and other variants of AM, which could enhance understanding of AM-BC.

PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts.

OBJECTIVE: Odontogenic keratocysts (OKCs) are benign jaw lesions with high growth potential and propensity for recurrence. Our previous study revealed that PTCH1 mutations, which were frequently detected in sporadic OKCs, might be underestimated due to the masking effect of the stromal components within the tested tissues. We aimed to confirm these results in larger scale and further present the unbiased view of the genomic basis of sporadic OKCs except PTCH1. MATERIALS AND METHODS: We analyzed PTCH1 mutations in additional 19 samples. Using whole-exome sequencing (WES), we further characterized the mutational landscape of five sporadic OKC samples lacking PTCH1 mutation and loss of heterozygosity (LOH). RESULTS: Combined with our previously reported 19 cases, thirty of 38 (79%) cases harbored PTCH1 mutations. Through whole-exome sequencing and integrative analysis, 22 novel mutations were confirmed among five PTCH1-negative samples. No recurrent mutations were identified in the WES samples and validation cohort of 10 OKCs. CONCLUSIONS: Our data further confirmed the frequent PTCH1 mutation and other rare genetic alterations in sporadic OKCs, highlighting the central role of SHH signaling pathway. In PTCH1-negative cases, other rare mutations scattered in a subset of OKCs were independent of the SHH pathway. These results suggested that an SHH inhibitor may be effective to treat the majority of OKCs.

Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts.

Odontogenic keratocyst (OKC) is a common jaw cyst with a high recurrence rate. OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome. Moreover, OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts. Because of the different prognosis, differential diagnosis of several cysts can contribute to clinical management. We collected 519 cases, comprising a total of 2 157 hematoxylin and eosin-stained images, to develop digital pathology-based artificial intelligence (AI) models for the diagnosis and prognosis of OKC. The Inception_v3 neural network was utilized to train and test models developed from patch-level images. Finally, whole slide image-level AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms. The AI models showed great performance in the diagnosis (AUC = 0.935, 95% CI: 0.898-0.973) and prognosis (AUC = 0.840, 95%CI: 0.751-0.930) of OKC. The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model. Furthermore, the study investigates the correlation between AI features generated by deep learning and pathological findings, highlighting the interpretative potential of AI models in the pathology. Here, we have developed the robust diagnostic and prognostic models for OKC. The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Alveolar bone height changes in the anterior tooth region before and after orthodontic treatment for Angle's Class II division 1 malocclusion and related factors.

BACKGROUND: The aim of this study was to observe the alveolar bone height changes in the anterior tooth region after orthodontic treatment for Angle's Class II division 1 malocclusion. METHODS: Ninety-three patients treated from January 2015 to December 2019 were retrospectively analyzed, of whom 48 received tooth extraction and 45 did not. RESULTS: After orthodontic treatment, the alveolar bone heights in the anterior tooth regions of tooth extraction and non-extraction groups decreased by 67.31% and 66.94%, respectively. Except for the maxillary and mandibular canines in the tooth extraction group as well as the labial side of maxillary anterior teeth and the palatal side of maxillary central incisors of the non-extraction group, the alveolar bone heights of other sites significantly reduced (P<0.05). The reduction in the alveolar bone height of the tooth extraction group significantly exceeded that of the non-extraction group on the palatal side of maxillary incisors and the lingual side of mandibular anterior teeth (P<0.05). CONCLUSIONS: Alveolar bone height in the anterior tooth region decreases after orthodontic treatment for Angle's Class II division 1 malocclusion, being closely related to tooth position together with movement direction and amplitude.

Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor: A Comparative Analysis.

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear ß-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic ß-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.

Head and neck carcinoma in children: A clinicopathological study of 42 cases.

Background/purpose: Cancer is an important part of the global burden of childhood diseases. Head and neck carcinoma in children is rare and related research is limited. This study aimed to investigate the clinicopathological features of childhood head and neck carcinoma. Materials and methods: Forty-two cases of childhood head and neck carcinoma treated in our institution were reviewed and analyzed. Results: Median age overall was 11 years. Twenty-three patients (54.8%) were male and 19 (45.2%) were female. Parotid gland location was most common (54.8%). Mucoepidermoid carcinoma and squamous cell carcinoma were the most common histological types (57.1% and 11.9%, respectively). Two patients had a history of bone marrow transplantation and two had a history of odontogenic keratocyst. The recurrence rate after treatment was 8.6%. Conclusion: Early diagnosis and treatment and close follow-up of childhood head and neck carcinoma are warranted to prevent recurrence and improve clinical outcome.

Clinicopathological and genetic study of a rare occurrence: Malignant transformation of fibrous dysplasia of the jaws.

BACKGROUND: Malignant transformation of fibrous dysplasia (FD) is very rare and little is known about this occurrence. METHODS: We present the detailed clinical course of three cases of osteosarcoma arising from FD of the jaws and explore the genetic aberrations by Sanger sequencing, whole-exome sequencing (WES) and immunohistochemistry (IHC). A literature review of important topics related to this occurrence was also performed. RESULTS: It was observed that patients with secondary sarcoma from FD showed a wide range of ages, with most during the third decade. Female and males were equally affected. Craniofacial bones and femurs were the most affected sites. High-risk factors for this occurrence included polyostotic FD, McCune-Albright syndrome and excess growth hormone. Notably, a potential relationship between thyroid hormones and sarcoma development was suggested in one patient, who began to show malignant features after hypothyroidism correction. Sanger sequencing revealed GNAS mutations of FD retained in all malignant tissues. Additionally, abnormal TP53 was demonstrated in all three cases by WES and IHC. WES also revealed two other driver mutations, ROS1 and CHD8, and large amounts of somatic copy number alterations (CNAs) where various oncogenes and tumour suppressors are located. CONCLUSION: This study demonstrated and reviewed the clinical features and risk factors for a rare occurrence, secondary sarcoma from FD, and provided important new knowledge about its genetics.

A three-in-one alveolar process reconstruction protocol for maxillary molar sites with severe residual bone height deficiency: A proof-of-concept pilot study.

BACKGROUND: Implant placement in maxillary molar sites with severe height deficiency often requires multiple surgeries, which was time-consuming, invasive, and subject to serious postoperative complications. PURPOSE: To introduce and assess a three-in-one technique (extraction, alveolar ridge preservation [ARP], and sinus elevation) for augmenting deficiency maxillary molar alveolar ridges. MATERIAL AND METHODS: Fourteen patients with severe posterior maxillary ridge height deficiency underwent extraction, sinus elevation via an intrasocket window and ARP using sticky bone and then covered with acellular dermal matrix (ADM). Primary closure was intentionally not obtained. Cone-beam computed tomography and periapical radiography were used to measure dimensional ridge changes over time. Bone biopsies were taken at implant placement 7-21 months after surgery, which proceeded without additional grafting. Peri-implant soft tissue was assessed after 8-12 months of functional loading. RESULTS: Maxillary molar sites (13 first molars, 1 second molar) with a mean sinus floor height of 1.73 ± 0.86 mm and mean buccal plate thickness of 1.62 ± 1.15 mm were elevated and grafted. Immediately after surgery, the mean sinus floor height was 14.03 ± 1.97 mm and the alveolar thickness at virtual implant platform level was 12.99 ± 1.88 mm. After 5-9 months healing, those measurements decreased by 2.45 ± 1.73 mm (p = 0.000) and 3.88 ± 3.95 mm (p = 0.006), respectively. Healed ridges were composed of 18.74% ± 4.34% mean vital bone and 19.08% ± 9.10% mean residual graft. After 8-12 months of functional loading, the peri-implant tissue appeared healthy, and there was a mean marginal bone loss of 0.12 ± 0.11 mm. CONCLUSIONS: For maxillary first molar sites with severe sinus floor height deficiency, this minimally invasive three-in-one treatment allows for uncomplicated implant placement and short-term functional stability.

Should the solid variant of odontogenic keratocyst and keratoameloblastoma be classified as the same entity? A clinicopathological analysis of nine cases and a review of the literature.

The solid variant of odontogenic keratocyst (SOKC) is an extremely rare odontogenic lesion, which remains poorly defined even in the 2017 World Health Organization odontogenic tumour classification. It is difficult to distinguish between SOKC and so called keratoameloblastoma (KAB), both rare lesions that have similarities in clinical, histological and biological characteristics. Here, we report clinicopathological data and results of molecular analysis of nine cases with a literature review. First, they were compared to previously reported cases of SOKC and/or KAB, and many overlaps were found in clinical and pathological characteristics. Second, we performed PCR analysis for BRAF V600E mutation. Although ameloblastoma-like epithelia were often encountered, none exhibited BRAF V600E mutation, which has been reported to occur frequently in ameloblastomas but not in odontogenic keratocysts (OKCs). One of two cases of SOKC in the present series from which fresh frozen tissue specimens were available was found to harbour PTCH1 mutations, indicating that these were more likely to be a subtype of OKC. Moreover, we also examined the differences between SOKC and primary intraosseous carcinoma (PIOC) with regard to the expression of cytokeratins (pan-CK, CK5/6, CK7, CK8/18, CK10, CK14 and CK19), p53 and Ki-67. The proportions of p53-and Ki-67-positive cells were significantly higher in PIOC than in SOKC. These findings suggest that immunostaining for p53 and Ki-67 would be useful to differentiate between SOKC and PIOC. We also conducted a review of SOKC and KAB cases reported in the English language literature.

Expression of vitamin D 1α-hydroxylase in human gingival fibroblasts in vivo.

BACKGROUND: Vitamin D 1α-hydroxylase CYP27B1 is the key factor in the vitamin D pathway. Previously, we analyzed the expression of CYP27B1 in human gingival fibroblasts in vitro. In the present study, we analyzed the gingival expression of CYP27B1 in vivo. METHODS: Forty-two patients with periodontitis Stage IV Grade C and 33 controls were recruited. All patients with periodontitis had unsalvageable teeth and part of the wall of the periodontal pocket was resected and obtained after tooth extraction. All controls needed crown-lengthening surgery, and samples of gingiva resected during surgery were also harvested. All the individuals' gingivae were used for immunohistochemistry and immunofluorescence. In addition, gingivae from seventeen subjects of the diseased group and twelve subjects of the control group were analyzed by real-time PCR. RESULTS: Expression of CYP27B1 was detected both in gingival epithelia and in gingival connective tissues, and the expression in connective tissues colocalized with vimentin, indicating that CYP27B1 protein is expressed in gingival fibroblasts. The expression of CYP27B1 mRNA in gingival connective tissues and the CYP27B1 staining scores in gingival fibroblasts in the diseased group were significantly higher than those in the control group. CONCLUSIONS: Expression of CYP27B1 in human gingival tissues was detected, not only in the fibroblasts of gingival connective tissues, but also in the gingival epithelial cells, and might be positively correlated with periodontal inflammation.