In light of the lack of reliable molecular markers for odontogenic myxoma (OM), the detection of copy number variation (CNV) may present a more objective method for assessing ambiguous cases. In this study, we employed multiregional microdissection sequencing to integrate morphological features with genomic profiling. This allowed us to reveal the CNV profiles of OM and compare them with dental papilla (DP), dental follicle (DF), and odontogenic fibroma (OF) tissues. We identified a distinct and robustly consistent CNV pattern in 93.75% (30/32) of OM cases, characterized by CNV gain events in chromosomes 4, 5, 8, 10, 12, 16, 17, 20, and 21. This pattern significantly differed from the CNV patterns observed in DP, DF, and OF. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated potential links between this CNV patterns and the calcium signaling pathway and salivary secretion, while Gene Ontology (GO) term analysis implicated CNV patterns in tumor adhesion, tooth development, and cell proliferation. Comprehensive CNV analysis accurately identified a case that was initially disputable between OF and OM as OM. Our findings provide a reliable diagnostic clue and fresh insights into the molecular biological mechanism underlying OM.
Humans ; DNA Copy Number Variations ; Odontogenic Tumors/diagnosis* ; Myxoma/genetics* ; Female ; Male ; Adult ; Adolescent ; Middle Aged ; Dental Papilla ; Young Adult ; Fibroma/genetics* ; Dental Sac ; Child

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.
Humans ; Ameloblastoma/diagnostic imaging* ; Deep Learning ; Diagnosis, Differential ; Radiography, Panoramic ; Retrospective Studies ; Odontogenic Cysts/diagnostic imaging* ; Odontogenic Tumors

Central granular cell odontogenic tumors (CGCOTs) are rare, benign, slowly growing odontogenic neoplasms. Due to their uncertain histogenesis, CGCOTs are still not included as a distinct entity in the WHO classification (2017) of odontogenic tumors. We report a case of CGCOT involving the right side of maxillary anterior region of a 39-year-old white female. Immunohistochemical staining showed that granular cells positively expressed CD68 and vimentin, and negatively expressed S-100 protein. Meanwhile, we searched PubMed, Google Scholar, and Scopus databases to summary the clinico-pathological features of 51 reported cases of CGCOT. The results showed that the granular cells of 28.6% cases were immunopositive for vimentin and CD68, and odontogenic epithelial cells were positive immunoreactivity for cytokeratin. These findings reinforced the mesenchymal origin of granular cells and the odontogenic nature of epithelium islands.
Humans ; Female ; Adult ; Vimentin ; Odontogenic Tumors/pathology* ; Epithelial Cells/pathology* ; Keratins

Odontogenic tumors are rare lesions with unknown etiopathogenesis. Most of them are benign, but local aggressiveness, infiltrative potential, and high recurrence rate characterize some entities. The MAP-kinase pathway activation can represent a primary critical event in odontogenic tumorigenesis. Especially, the BRAF V600E mutation has been involved in 80-90% of ameloblastic lesions, offering a biological rationale for developing new targeted therapies. The study aims to evaluate the BRAF V600E mutation in odontogenic lesions, comparing three different detection methods and focusing on the Sequenom MassARRAY System. 81 surgical samples of odontogenic lesions were subjected to immunohistochemical analysis, Sanger Sequencing, and Matrix-Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (Sequenom). The BRAF V600E mutation was revealed only in ameloblastoma samples. Moreover, the presence of BRAF V600E was significantly associated with the mandibular site (ρ = 0.627; P value <0.001) and the unicystic histotype (ρ = 0.299, P value <0.001). However, any significant difference of 10-years disease-free survival time was not revealed. Finally, Sequenom showed to be a 100% sensitive and 98.1% specific, suggesting its high-performance diagnostic accuracy. These results suggest the MAP-kinase pathway could contribute to ameloblastic tumorigenesis. Moreover, they could indicate the anatomical specificity of the driving mutations of mandibular ameloblastomas, providing a biological rational for developing new targeted therapies. Finally, the high diagnostic accuracy of Sequenom was confirmed.
Ameloblastoma/pathology* ; Carcinogenesis ; Humans ; Mitogen-Activated Protein Kinases/genetics* ; Mutation ; Odontogenic Tumors/pathology* ; Proto-Oncogene Proteins B-raf/metabolism* ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective: To improve the understanding of histological variants of calcifying epithelial odontogenic tumor (CEOT). Methods: In this retrospective study, 11 cases of CEOT diagnosed from January 2008 to March 2022 were enrolled in the Department of Oral Pathology of Nanjing Stomatological Hospital, Medical School of Nanjing University. Among them, 10 were male and 1 was female. The patients were 19 to 58 years old [(43.0±11.9) years] and the course of disease was 2 weeks to 5 years. The clinicopathological characteristics were analyzed and the follow-up of patients ranged from 1 to 8 years, including 8 cases with follow-up data and 3 cases lost to follow-up. Furthermore, the related domestic and international literature was reviewed. Results: Eleven cases of CEOT included 6 cases of classic CEOT, 2 cases of clear cell CEOT, 2 cases of Langerhans cell-rich variant of CEOT and 1 case of non-calcified CEOT. In 6 cases of classic CEOT, the ratio of occurrence in mandible to maxilla was 2∶1, the ratio in central parts to peripheral parts was 5∶1, 2 cases were associated with unerupted teeth and 3 cases showed local aggressiveness. Histopathologically, classic CEOT showed eosinophilic epithelial cells, amyloid and calcification with Ki-67 value<5%. Among 4 cases with follow-up information, 1 case recurred after 1 year and 3 cases did not recur for 3 to 8 years. In 2 cases of clear cell CEOT, they both occurred in the periphery of mandible, pathologically showing a mix of lamellar balloon-like clear cells and typical CEOT, positive for CK5/6 and p63 in the area where the epithelial cells and clear cells were located, scattered positive for periodic acid-Schiff (PAS) in clear cells, which indicated the presence of glycogen. The maximum Ki-67 value was 5% in this type. One case lost to follow-up and the other case did not recur for 1 year follow-up after surgery. In 2 cases of Langerhans cell-rich variant of CEOT, they were cystic solid lesions and both occurred in the anterior maxilla. Langerhans cells were scattered in the epithelium and non-calcified amyloid glomeruli were present. Two cases were followed up for 1 year and 2 years without recurrence after surgery. One case of non-calcified CEOT that occurs within the jan showed invasion of surrounding soft tissues and the highest of Ki-67 value at 8% in all 11 cases without recurrence at 1 year follow-up. Conclusions: The histological pattern of classic CEOT is unique, and it is necessary to prompt the understanding of several histological variants derived from it.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Retrospective Studies ; Ki-67 Antigen ; Odontogenic Tumors/surgery* ; Skin Neoplasms/pathology*

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247_1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.
Basal Cell Nevus Syndrome/genetics* ; Female ; Humans ; Male ; Mutation ; Odontogenic Cysts/genetics* ; Odontogenic Tumors/genetics* ; Smoothened Receptor/genetics*

Fibroma/diagnostic imaging* ; Humans ; Odontogenic Tumors/diagnostic imaging* ; Tuberous Sclerosis/complications*

Peripheral odontogenic keratocysts are rarely observed, and cases of odontogenic keratocysts of buccal soft tissues are even rarer. This study was performed to present two rare cases of odontogenic keratocysts in buccal soft tissues and review related literature.
Humans ; Odontogenic Cysts/diagnosis* ; Odontogenic Tumors

Among the ghost cell lesions, Dentinogenic Ghost Cell Tumors (DGCT) are among the rarest. We report a case of a 45-year-old Filipino man, who presented with a right mandibular mass. Microscopic examination showed a solid neoplasm composed of islands of odontogenic epithelium with areas showing aberrant keratinization forming ghost cells and dentinoid material. We also discuss the pertinent differential diagnosis of ghost cell-containing odontogenic tumors. We report this case due to its rarity, its morphological resemblance to ameloblastoma, and its potential for malignant transformation.
Odontogenic Cysts ; Odontogenic Tumors

A 37-year-old woman consulted for a slow-growing mass of one-year duration on the left side of the mandible with associated tooth mobility. Clinical examination showed buccal expansion along the left hemi-mandible from the mid-body to the molar-ramus region with associated mobility and displacement of the pre-molar and molar teeth. Radiographs showed a well-defined unilocular radiolucency with root resorption of the overlying teeth. Decompression and unroofing of the cystic lesion was performed. Received in the surgical pathology laboratory were several gray-white rubbery to focally gritty tissue fragments with an aggregate diameter of 1 cm. Histopathologic examination shows a fibrocollagenous cyst wall lined by a fairly thin and flat stratified squamous epithelium without rete ridges. (Figure 1) The epithelium is parakeratinized with a wavy, corrugated surface while the basal layer is cuboidal and quite distinct with hyperchromatic nuclei. (Figure 2) Based on these features, we signed the case out as odontogenic keratocyst (OKC). Odontogenic keratocysts are the third most common cysts of the gnathic bones, comprising up to 11% of all odontogenic cysts, and most frequently occurring in the second to third decades of life.1,2 The vast majority of cases occur in the mandible particularly in the posterior segments of the body and the ramus. They typically present as fairly large unilocular radiolucencies with displacement of adjacent or overlying teeth.1 If associated with an impacted tooth the radiograph may mimic that of a dentigerous cyst.2 Microscopically, the parakeratinized epithelium without rete ridges, and with a corrugated luminal surface and a prominent cuboidal basal layer are distinctive features that enable recognition and diagnosis.1,2,3 Occasionally, smaller “satellite” or “daughter” cysts may be seen within the underlying supporting stroma, sometimes budding off from the basal layer. Most are unilocular although multilocular examples are encountered occasionally.1 Secondary inflammation may render these diagnostic features unrecognizable and non-specific.2 Morphologic differential diagnoses include other odontogenic cysts and unicystic ameloblastoma. The corrugated and parakeratinized epithelial surface is sufficiently consistent to allow recognition of an OKC over other odontogenic cysts, while the absence of a stellate reticulum and reverse nuclear polarization will not favor the latter diagnosis.2,3 Odontogenic keratocysts are developmental in origin arising from remnants of the dental lamina. Mutations in the PTCH1 gene have been identified in cases associated with the naevoid basal cell carcinoma syndrome as well as in non-syndromic or sporadic cases.1,3 These genetic alterations were once the basis for proposing a neoplastic nature for OKCs and thus the nomenclature “keratocystic odontogenic tumor” was for a time adopted as the preferred name for the lesion.3,4 Presently, it is felt there is not yet enough evidence to support a neoplastic origin and hence the latest WHO classification reverts back to OKC as the appropriate term.1 Sekhar et al. gives a good review of the evolution of the nomenclature for this lesion.3 Treatments range from conservative enucleation to surgical resection via peripheral osteotomy.5 Reported recurrences vary in the literature ranging from less than 2% of resected cases up to 28% for conservatively managed cases.1,5 These are either ascribed to incomplete removal or to the previously mentioned satellite cysts - the latter being a feature associated with OKCs that are in the setting of the naevoid basal cell carcinoma syndrome.1,2,3 Thus, long term follow-up is recommended.5 Malignant transformation, though reported, is distinctly rare.
odontogenic cyst ; odontogenic tumors ; Basal Cell Nevus Syndrome