Odontogenic Myxomas Harbor Recurrent Copy Number Alterations and a Distinct Methylation Signature.

Odontogenic myxoma is a rare, benign, and locally aggressive tumor that develops in the tooth-bearing areas of the jaw. The molecular mechanisms underlying odontogenic myxomas are unknown and no diagnostic markers are available to date. The aim of this study was to analyze DNA methylation and copy number variations in odontogenic myxomas to identify new molecular signatures for diagnostic decision-making. We collected a cohort of 16 odontogenic myxomas from 2006 to 2021 located in the mandible (n = 10) and maxilla (n = 6) with available formalin-fixed paraffin-embedded or fresh frozen tumor tissue from a biopsy or resection material. Genome-wide DNA methylation and copy number variation data were generated from 12 odontogenic myxomas using the Illumina Infinium Methylation EPIC array, interrogating >850,000 CpG sites. Unsupervised clustering and dimensionality reduction (Uniform Manifold Approximation and Projection) revealed that odontogenic myxomas formed a distinct DNA methylation class. Copy number profiling showed recurrent whole-chromosome gains (trisomies) of chromosomes 5, 8, and 20 in all cases, and of chromosomes 10, 12, and 17 in all except one case. In conclusion, odontogenic myxomas harbor recurrent copy number patterns and a distinct DNA methylation profile, which can be used as an additional diagnostic tool in the appropriate clinical and radiologic context. Further research is needed to explain the genetic mechanisms caused by these alterations that drive these locally aggressive neoplasms.

Intraosseous myofibroma mimicking an odontogenic lesion: case report, literature review, and differential diagnosis.

BACKGROUND: Intraosseous myofibroma of the jaw is a rare neoplasm of mesenchymal origin with limited comprehensive understanding. It typically affects patients in the first two decades of life with a male predilection. CASE PRESENTATION: This study presents a rare case of myofibroma mimicking an odontogenic lesion in a 2-year-old boy. The patient presented with an incidental finding of a painless swelling of the right mandibular ramus of unknown etiology. Imaging analysis revealed a solid, expansile lesion adjacent to the germinal zone of the right mandibular first molar. Histopathologic analysis and immunohistochemistry after incisional biopsy suggested a possible central odontogenic fibroma, and the patient underwent total enucleation, leading to the final diagnosis of intraosseous myofibroma. Follow-up examinations showed no evidence of recurrence. CONCLUSIONS: This report contributes to the understanding of myofibroma in pediatric patients and underscores the critical role of meticulous histopathologic examination for effective surgical planning and optimal patient outcomes.

Establishment of an Animal Model of Oral Squamous Cell Carcinoma Invading the Mandible.

OBJECTIVE: To establish an animal model of oral squamous cell carcinoma invading the mandible through multi-sample experiments that verified the stability, repeatability, tumorigenicity and mandible destruction rate of the model. METHODS: Oral squamous cell carcinoma cell suspension was injected into the outer side of the mandible through the anterior edge of the masseter muscle of naked mice to observe the tumourforming process. Then, the anatomical, histological and imaging examinations were carried out to determine whether the tumour had invaded the mandible. By comparing the tumour growth of multiple groups of various squamous cell carcinoma cells (CAL27, HN6 and HN30 cells), the changes in body weight and characteristics of tumour formation were compared, and the experience was summarised to further verify the stability, repeatability, tumour formation rate and arch damage rate of the model. RESULTS: The subsequent specimens of tumour-bearing nude mice were validated once the model had been established. In vitro, tumour tissue wrapped around the mandible's tumour-bearing side, and the local texture was tough with no resistance to acupuncture. Haematoxylin and eosin staining revealed that squamous cells were infiltrating the mandible in both the horizontal and sagittal planes. Microcomputed tomography results showed that the mandible on the tumour-bearing side displayed obvious erosion damage. Cell lines with various passage rates clearly had diverse tumour-bearing life cycles. CONCLUSION: This study successfully established an animal model of oral squamous cell carcinoma invasion of the mandible. The model has excellent biological stability, repeatability, tumorigenesis rate and mandible destruction rate.

Unicystic ameloblastoma: Clinico-radiological and histopathological correlation with management.

Unicystic ameloblastoma is a distinct entity of ameloblastoma characterized by slow growth and locally aggressive behavior. This retrospective study aimed to assess the efficacy of different treatment modalities of unicystic ameloblastoma, focusing on clinico-radiological and histopathological features. Data from patients diagnosed with unicystic ameloblastoma were retrospectively analyzed. Patients were categorized into luminal and intraluminal (Group A) and mural (Group B) variants based on the Ackermann classification, which has a significant influence on their biological behavior, treatment approaches, and prognosis. Patients in Group A underwent enucleation with chemical cauterization, peripheral ostectomy, and iodoform packing, whereas those in Group B were treated with resection and reconstruction. Post-operatively, the patients were subjected to radiographic assessments via digital orthopantomogram at regular intervals. Because of the rarity of unicystic ameloblastoma, only 17 patients were included in the study (Group A: 9 patients; Group B: 8 patients), with a mean follow-up of 4.9 years (range: 1.4-11.8 years). The primary outcome measure was the absence of recurrence, which indicated treatment success. No patient in either group experienced recurrence within the follow-up period. This study provides evidence supporting the successful treatment of luminal and intraluminal variants of unicystic ameloblastoma in young individuals using a conservative approach. However, the more aggressive mural variant demonstrated favorable outcomes with radical treatment. These findings emphasize the importance of the Ackermann classification in guiding treatment decisions for unicystic ameloblastoma and contribute valuable insights into optimizing therapeutic strategies based on clinico-radiological and histopathological findings.

[Clincopathological analysis of 171 patients with osteochondroma and malignant transformation in maxillofacial bone].

PURPOSE: To investigate the clinical and pathological features of osteochondroma in maxillofacial region, and to summarize the clinicopathological features of rare osteochondroma malignant transformation in order to provide clinical guidance. METHODS: From January 2018 to September 2023, a total of 171 patients with osteochondroma were retrospectively collected in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Their preoperative CT and clinicopathological features were analyzed. RESULTS: Of the 171 patients with osteochondroma in maxillofacial bone, 66%（113/171） were females and 34% were male. Their age ranged from 11-76 with an average age was 44 years old. Of the 171 cases, 95.3%（163/171）in mandible condyle, 4%(7/171) in mandible processus coronoideus, and 0.5%（1/171） in zygomatic arch. The imaging findings showed that the thickness of cartilaginous cap was less than 1 cm in 98%（159/161） cases with condyle lesions. Only 2 cases(2/171, 1.1%) had malignant transformation. One was diagnosed with secondary chondrosarcoma, another developed low-grade osteosarcoma. CONCLUSIONS: Osteochondroma in maxillofacial region mostly occurs in females, and most commonly located in condylar process, with a malignant change rate of 1.1%, which is similar to that of other parts of the body. Imaging findings have important guiding significance for the diagnosis of osteochondroma malignant change.

Large Complex Odontoma in the Angulus Mandibulae - Intraoral Enucleation as an Alternative to Mandibular Continuity Resection.

BACKGROUND: Odontomas are among the most common odontogenic tumors and are generally considered as hamartomatous odontogenic lesions. These tumors can be histopathologically divided into complex odontomas and compound odontomas based on their composition. Odontomas show a slow growing behavior and typically lack characteristic symptoms. The standard surgical treatment for large odontogenic tumors is a mandibular (continuity) resection followed by primary or secondary plastic reconstruction. CASE REPORT: A 22-year-old male presented to the Department of maxillofacial surgery with an increasing feeling of pressure in the left mandible. An orthopantomogram revealed a large complex odontoma rg 038. Instead of mandible continuity resection an alternative minimally invasive technique/approach (intraoral) with a trapezoidal bone flap for the enucleation of an odontoma of the mandibular angle with subsequent flap reimplantation and osteosynthesis was performed. CONCLUSION: Surgical enucleation of large mandibular odontoma with a continuity resection through an extraoral approach represents the surgical standard treatment of this entity. The present case report describes an alternative minimally invasive technique/approach. This technique may reduce surgical risks of the continuity resection through an extraoral approach (nerve damage, scarring) and can improve the long-term stability of the mandible by bone preservation.

Synchronous cemento-ossifying fibromas: a systematic review.

BACKGROUND: This systematic review aimed to incorporate published data regarding synchronous cemento-ossifying fibromas (COF), with an analysis of their demographic and clinicopathological characteristics. MATERIAL AND METHODS: Case reports and case series of synchronous COF were searched in PubMed, Web of Science, Scopus, EMBASE, and LILACS according to the PRISMA (2020) statement. Also, a manual search was carried out and the grey literature was assessed. A descriptive statistical analysis was performed. RESULTS: Nineteen studies comprising 20 cases of synchronous COF were included. The mean age at diagnosis was 35 years (±13.8), with a predominance of female patients (n=12/60%). In 13 cases (65%) the mandible and the maxilla were affected simultaneously. In two cases (10%) first-degree relatives (parents or siblings) had been previously diagnosed with COF. The diagnostic hypotheses were reported in 8 cases (40%), with florid cemento-osseous dysplasia, ameloblastic fibroodontoma, calcifying cystic odontogenic tumor, osteoma and cementoblastoma being cited in the differential diagnosis. Among the cases with details about management (n=17), eleven were treated by surgical enucleation and/or excision (64.7%). Follow-up was provided for 10 cases (50%), with a mean period of 44.7±62.19 months. Recurrence occurred in three of informed cases. CONCLUSIONS: Synchronous manifestation of COF is rare. Female patients around the 3rd decade of life are more commonly affected. Bilateral involvement of the mandible and maxilla is the most common clinical presentation.

Ossifying fibroma: the peripheral variant.

Introduction: Peripheral ossifying fibroma (POF) is a solitary gingival growth thought to arise from the gingiva, periosteum or the periodontal ligament. It is a slow-growing, benign, progressive lesion that is limited in size. Case description: This article describes a case of ossifying fibroma of a peripheral variant that occurred in a 26-year-old female in the anterior region of the lower jaw and presented as a growth on the gingiva. Since it was difficult to diagnose clinically, a pathological evaluation was mandatory. Upon pathological confirmation of the diagnosis, the lesion was surgically excised up to the periosteum. This was deemed to be the required treatment yet, since the recurrence rate is high for POF (8% to 20%), the patient must be followed up yearly to check for recurrence.

Introduction: Le fibrome ossifiant périphérique (FOP) est une excroissance gingivale solitaire dont on pense qu'elle provient des gencives, du périoste ou du ligament parodontal. Il s'agit d'une lésion progressive, bénigne et à croissance lente dont la taille est limitée. Description du cas: Cet article décrit le cas d'une variante périphérique du fibrome ossifiant survenue chez une femme de 26 ans, dans la région antérieure de sa mâchoire inférieure et se présentant comme une excroissance sur la gencive. Comme il était difficile d'établir un diagnostic clinique, une évaluation pathologique a été nécessaire. Après confirmation pathologique du diagnostic, la lésion a été excisée jusqu'au périoste lors d'une opération chirurgicale. On a jugé ce traitement nécessaire, puisque le taux de récidive du FOP est élevé (entre 8 % et 20 %). La patiente doit faire l'objet d'un suivi annuel pour rechercher toute récidive éventuelle.

Giant cell granuloma and neurofibroma in the mandible of a patient with neurofibromatosis type 1: a long-term follow-up case report with radiological and surgical aspects and a review of the literature.

BACKGROUND: Magnetic resonance imaging (MRI) of the brain is frequently performed on patients with neurofibromatosis type 1 (NF1), to detect and follow-up intracranial findings. In addition, NF1-related pathologies can appear in the jaws. This case study investigates if it is advantageous to assess the depicted parts of the jaws in the imaging of NF1 patients with intracranial findings, thereby detecting jaw pathologies in their initial stages. CASE PRESENTATION: We report on the 3-year management with clinical and radiological follow-ups of a central giant cell granuloma and a neurofibroma in the mandible of a patient with NF1 who underwent examinations with brain MRIs. A review of the mandible in the patient's MRIs disclosed lesions with clear differences in progression rates. CONCLUSION: NF1-related jaw pathologies may be detected in the early stages if the depicted parts of the jaws are included in the assessment of the imaging of NF1 patients with intracranial findings. This could impact the treatment of eventual pathologies before lesion progression and further damage to the vicinity.

Telangiectatic osteosarcoma of the mandible-A rare case report and an insight into differential diagnosis.

Telangiectatic osteosarcoma (TOS) is a rare variant of osteosarcoma that typically affects young individuals and long bones. The case under discussion was seen in the mandible of a 57-year-old female and had rapidly grown in size within a week. Microscopically, the tumour was characterised by large vascular cavities surrounded by anaplastic cells. Thin lacy tumour osteoid was observed at various foci. Abundant multinucleated osteoclastic giant cells along with areas of necrosis were also noted. The tumour cells were positive for SATB2, while negative for Cytokeratin AE1/3, CD 34. Ki-67 positivity was observed in more than 50% of tumour cells. A diagnosis of high grade telangiectatic osteosarcoma was thus made.

Carbon-ion radiotherapy for clear cell odontogenic carcinomas.

BACKGROUND: Clear cell odontogenic carcinoma (CCOC) is a rare odontogenic malignant tumor. The standard treatment for CCOC is surgical resection and adjuvant radiotherapy (RT). Radiotherapy is generally considered in inoperable cases. However, there are no reports on definitive RT for CCOC, and the role of RT in patients with inoperable CCOC remains unknown. Therefore, in this report, we present two cases of carbon-ion (C-ion) RT for CCOC. CASE PRESENTATION: In case 1, a 73-year-old man with mandibular CCOC presented with recurrence in the inferior temporal fossa after two tumor resections. The tumor was considered inoperable, and C-ion RT (57.6 Gy in 16 fractions) was administered. The tumor remained controlled even after 20 months of C-ion RT; however, the patient died of other causes. In case 2, a 34-year-old man with maxillary CCOC presented with recurrence in the left sinonasal region after two tumor resections. The tumor was considered inoperable, and C-ion RT (64 Gy in 16 fractions) was administered. However, recurrence was observed in the irradiated field 19 months after the treatment. Subsequently, C-ion RT (64 Gy in 16 fractions) was repeated for the recurrent tumors. Seven years and 6 months after the initial irradiation, the tumor remains controlled, and the patient is alive without any unexpected serious adverse events. CONCLUSION: C-ion RT may be an effective treatment option for patients with inoperable CCOC.

Odontome and its pathological effect on surrounding teeth.

Odontoma is the most common odontogenic tumour derived from both epithelial and mesenchymal components of the tooth-forming apparatus. It is commonly diagnosed in the second and third decades of life when a radiograph is taken for some other purpose, as most cases are asymptomatic. This case involves a young boy, with the chief complaint of pain and swelling in the lower left back region. An intraoral examination revealed a carious and hypoplastic left permanent mandibular first molar. Although the molar was suspected as the source of his symptoms, radiographic imaging revealed multiple odontomas and missing second and third molar tooth buds. This case highlights the pathological effects of odontomas on surrounding teeth, including the malformation of the first molar and aplasia of the second and third molars. The sole management depends on the early diagnosis, histopathological examination to rule out malignancy and conservative surgical excision of these tissues.

Adenoid Ameloblastoma: The Newly Recognized Odontogenic Tumor - A Case Report.

Adenoid ameloblastoma is a newly recognized epithelial odontogenic tumor. Herein, we present the case of a 24-year-old male patient who exhibited swelling in the anterior region and right hemi-mandible. Computed tomography demonstrated the presence of a hypodense osteolytic lesion associated with an impacted tooth. Based on the clinical hypotheses of the dentigerous cyst, odontogenic keratocyst, and ameloblastoma, an incisional biopsy was performed, and the diagnosis of ameloblastoma was rendered. A surgical resection of the tumor was performed. Histopathological examination of the specimen revealed typical areas of ameloblastoma associated with ductiform structures and cell proliferation in a solid storiform pattern, features resembling those found in adenomatoid odontogenic tumor. Based on these findings, the diagnosis of adenoid ameloblastoma was rendered. The accurate diagnosis of this locally infiltrative tumor is essential due to its similarity to other odontogenic neoplasms.

[Komplexes Odontom im Unterkieferfrontzahnbereich bei einer 16-jährigen Patientin - Diagnostik, Therapie und Nachsorge].

Odontome gelten zusammen mit den Amelo- blastomen als die häufigsten odontogenen Tumoren. Sie entstehen während der embryo- nalen Zahnkeimentwicklung durch fehlerhaft differenziertes Keimgewebe und werden daher auch als Hamartome bezeichnet. Somit sind sie also strenggenommen keine klassischen Neoplasien.

Wnt/ß-catenin-YAP axis in the pathogenesis of primary intraosseous carcinoma NOS, deriving from odontogenic keratocyst.

Odontogenic tumors (OGTs), which originate from cells of odontogenic apparatus and their remnants, are rare entities. Primary intraosseous carcinoma NOS (PIOC), is one of the OGTs, but it is even rarer and has a worse prognosis. The precise characteristics of PIOC, especially in immunohistochemical features and its pathogenesis, remain unclear. We characterized a case of PIOC arising from the left mandible, in which histopathological findings showed a transition from the odontogenic keratocyst to the carcinoma. Remarkably, the tumor lesion of this PIOC prominently exhibits malignant attributes, including invasive growth of carcinoma cell infiltration into the bone tissue, an elevated Ki-67 index, and lower signal for CK13 and higher signal for CK17 compared with the non-tumor region, histopathologically and immunohistopathologically. Further immunohistochemical analyses demonstrated increased expression of ADP-ribosylation factor (ARF)-like 4c (ARL4C) (accompanying expression of ß-catenin in the nucleus) and yes-associated protein (YAP) in the tumor lesion. On the other hand, YAP was expressed and the expression of ARL4C was hardly detected in the non-tumor region. In addition, quantitative RT-PCR analysis using RNAs and dot blot analysis using genomic DNA showed the activation of Wnt/ß-catenin signaling and epigenetic alterations, such as an increase of 5mC levels and a decrease of 5hmC levels, in the tumor lesion. A DNA microarray and a gene set enrichment analysis demonstrated that various types of intracellular signaling would be activated and several kinds of cellular functions would be altered in the pathogenesis of PIOC. Experiments with the GSK-3 inhibitor revealed that ß-catenin pathway increased not only mRNA levels of ankyrin repeat domain1 (ANKRD1) but also protein levels of YAP and transcriptional co-activator with PDZ-binding motif (TAZ) in oral squamous cell carcinoma cell lines. These results suggested that further activation of YAP signaling by Wnt/ß-catenin signaling may be associated with the pathogenesis of PIOC deriving from odontogenic keratocyst in which YAP signaling is activated.

Aggressive Late Recurrence of a Calcifying Epithelial Odontogenic Tumor: Surgical Refinements Based on New Technologies.

A calcifying epithelial odontogenic tumor is a rare, benign odontogenic neoplasm. Surgical treatment is the option, and late recurrence is very rare. Radiologically, the lesions are commonly present scattered calcifications. This case report details a 64-year-old female patient with a recurrence of a right mandibular calcifying epithelial odontogenic tumor 2 decades after successful initial surgical removal. A segmental mandibulectomy and immediate reconstruction were performed using a planned vascularized free fibula flap with virtual surgery, custom reconstruction plate, and intraoperative computed tomography. Modifications were made to the design of the reconstruction plate to improve the cervicofacial profile and subsequent rehabilitation with dental implants. Fully guided implant surgery with point-of-care manufacturing protocol was done to improve prosthetically driven implant planning. The case presented highlights the usefulness of new technologies for mandibular reconstruction with the free fibula flap and the concept of point-of-care with technical notes that increase precision and reduce morbidity in implant-supported rehabilitation.

Odontogenic carcinoma with dentinoid: case report and literature review of a rare entity.

BACKGROUND: Odontogenic carcinoma with dentinoid (OCD) is a rare and controversial entity, which has not yet been included in the current World Health Organization classification of odontogenic lesions. Owing to the small number of reported cases, the clinicopathological characteristics, biological behavior, prognosis, and appropriate treatment strategies for OCD remain to be defined. Herein, we present an additional case of OCD with a focus on the differential diagnosis and review of the pertinent literature, in order to enable better recognition by oral clinicians and pathologists and further characterization of this entity. CASE PRESENTATION: This paper reports a case of OCD in the posterior mandible of a 22-year-old female. Radiography showed a well-defined unilocular radiolucency with radiopaque materials. The intraoperative frozen section pathology gave a non-committed diagnosis of odontogenic neoplasm with uncertain malignant potential. Then a partial mandibulectomy with free iliac crest bone graft and titanium implants was performed. Microscopically, the tumor consisted of sheets, islands, and cords of round to polygonal epithelial cells associated with an abundant dentinoid matrix. Immunohistochemically, the tumor cells were diffusely positive for CK19, p63, and ß-catenin (cytoplasmic and nuclear). No rearrangement of the EWSR1 gene was detected. The final diagnosis was OCD. There has been no evidence of recurrence or metastasis for 58 months after surgery. We also provide a literature review of OCD cases, including one case previously reported as ghost cell odontogenic carcinoma from our hospital. CONCLUSIONS: OCD is a locally aggressive low grade malignancy without apparent metastatic potential. Wide surgical excision with clear margins and long-term period follow-up to identify any possible recurrence or metastases are recommended. Histopathological examination is essential to conclude the diagnosis. Special care must be taken to distinguish OCD from ghost cell odontogenic carcinoma and clear cell odontogenic carcinoma, as misdiagnosis might lead to unnecessary overtreatment. Study of additional cases is required to further characterize the clinicopathological features and clarify the nosologic status and biological behavior of this tumor.

Central giant cell granuloma in the posterior region of mandible mimicking a fibro-osseous lesion and hemangioma: a case report.

BACKGROUND: A central giant cell granuloma (CGCG) is a benign, proliferative, intraosseous, and non-odontogenic lesion occurring primarily in children and young adults. On the histological level, it is characterized by numerous multinucleated giant cells scattered randomly throughout a sea of spindle-shaped mesenchymal stromal cells which are dispersed throughout the fibrovascular connective tissue stroma containing areas of haemorrhage. When it comes to radiographic features, CGCG can have an array of variations, ranging from well-defined expansile lesions to ill-defined and destructive lesions, with or without expansion. CASE PRESENTATION: This case report reviews an 11-year-old Caucasian patient with a chief complaint of slow-growing swelling involving the right posterior mandibular region. The cone beam computed tomography (CBCT) revealed an ill-defined mixed lesion mimicking both fibro-osseous lesion and hemangioma. However, microscopic examination revealed multinucleated giant cells in a fibrous stroma suggestive of central giant cell granuloma. CONCLUSION: Our intent in reporting this case is to highlight the importance of thorough clinical, radiographical and histopathological examination for accurate diagnosis and therapeutic interventions as well as to emphasize the importance of taking different possibilities into consideration when examining bony swellings in the head and neck region.