Frequency and Demographic Analysis of Odontogenic Tumors in Three Tertiary Institutions: An 11-Year Retrospective Study.

Odontogenic tumors (OTs) are distinct conditions that develop in the jawbones, exhibiting diverse histopathological features and variable clinical behaviors. Unfortunately, the literature on this subject in Saudi Arabia remains sparse, indicating a pressing need for more comprehensive data concerning the frequency, demographics, treatment modalities, and outcomes of OTs. OBJECTIVES: The study aims to evaluate the frequency, demographic features, treatment, and outcomes of OTs across three tertiary medical centers. METHODS AND MATERIAL: OT cases were identified in King Abdulaziz Medical City (KAMC), King Fahad Medical City (KFMC), and Prince Sultan Military Medical City (PSMMC) from January 2010 to December 2021. RESULTS: Ninety-two OT cases were identified from the anatomical pathology laboratories of three tertiary hospitals. KFMC contributed the highest number of cases (43.5%), followed by KAMC (30.4%) and PSMMC (26.1%). The median age of OT patients was 29 years (range: 5-83), with males representing more than half of the patients (56.5%). The mandible was the most frequent site of OT occurrence (72.5%), with ameloblastoma being the predominant OT (63.0%), followed by odontoma (19.5%). Among the treatment modalities, bone resection was employed the most (51.0%), followed by enucleation (25.6%). Notably, 11.5% of OT cases with available follow-up data exhibited recurrence, with ameloblastoma accounting for eight recurrent cases. CONCLUSIONS: Although OTs are relatively common in the jaws, they are rare in anatomical pathology laboratories and the general population. This study contributes valuable insights into the epidemiology characteristics, treatment trends, and recurrence rates of OTs in Saudi Arabia.

Tumor microenvironment of ameloblastoma with a focus on osteoclastogenesis, cell migration, and malignant transformation.

BACKGROUND: Odontogenic tumors arise in the jawbone and originate from cells associated with tooth development. Therefore, understanding odontogenic tumors requires knowledge of all aspects of dental research, including tooth development and eruption. Ameloblastoma is the most common odontogenic tumor. HIGHLIGHT: Although a benign tumor, ameloblastoma progresses with marked jawbone resorption. Because of its locally aggressive features, it can be treated surgically by resecting the surrounding bone. From a molecular pathology perspective, several genetic mutations and dysregulated signaling pathways involved in ameloblastoma tumorigenesis have been identified. Histopathologically, ameloblastomas consist of peripheral ameloblast-like cells and an inner stellate reticulum. The stromal region consists of fibrovascular connective tissue, showing a characteristic sparse myxoid histology. In general, the tumor microenvironment, including the surrounding non-tumor cells, contributes to tumorigenesis and progression. In this review, we focus on the tumor microenvironment of ameloblastomas. In addition, we present some of our recent studies on osteoclastogenesis, tubulin acetylation-induced cell migration, and hypoxia-induced epithelial-mesenchymal transition in ameloblastomas. CONCLUSION: Further research on ameloblastomas can lead to the development of new treatments and improve patients' quality of life.

Targeted therapies in ameloblastomas and amelobastic carcinoma-A systematic review.

Targeted therapy has the potential to be used in the neoadjuvant setting for odontogenic tumors, reducing the morbidities associated with major surgery. In this regard, the aim of this study was to summarize the current evidence on the different forms of targeted therapy, effectiveness, and drawbacks of this course of treatment. Four databases were searched electronically without regard to publication date or language. Grey literature searches and manual searches were also undertaken. Publications with sufficient clinical data on targeted therapy for odontogenic tumors were required to meet the criteria for eligibility. The analysis of the data was descriptive. A total of 15 papers comprising 17 cases (15 ameloblastomas and 2 ameloblastic carcinomas) were included. Numerous mutations were found, with BRAF V600E being most common. Dabrafenib was the most utilized drug in targeted therapy. Except for one case, the treatment reduced the size of the lesion (16/17 cases), showing promise. Most of the adverse events recorded were mild, such as skin issues, voice changes, abnormal hair texture, dry eyes, and systemic symptoms (e.g., fatigue, joint pain, and nausea). It is possible to reach the conclusion that targeted therapy for ameloblastoma and ameloblastic carcinoma may be a useful treatment strategy, based on the findings of the included studies.

Malignant transformation of primary ameloblastoma of skull: case report and review of current literature.

Background: Since 1964, there has been a scarcity of reported cases of primary ameloblastoma (AM) or ameloblastic carcinoma (AMCa) of the skull. The clinical presentation and distinctive features of this uncommon condition at specific anatomical sites remain unclear. We report a case of malignant transformation of a primary AM of the skull situated in the frontal-temporal-parietal region and highlight its similarities to other cases reported in the literature. Clinical presentation: A 53-year-old female patient presented with a 20-day history of headaches and bilateral lower limb weakness for 10 days. Physical examination revealed slow and unsteady gait. An occupying lesion was observed in the right frontal-temporal-parietal region of the skull on the Cranial imaging. A right cranial bone tumor margin expansion resection was performed. The patient's motor functions recovered normally after surgery. Postoperative imaging examinations showed10 tumor resection. Follow-up imaging examinations showed tumor recurrence. The patient underwent resection of the recurrent tumor. Postoperative pathological analysis revealed malignant transformation of the AM.Follow-up imaging examinations showed tumor recurrence again. The patient was admitted for stereotactic radiotherapy. Follow-up imaging examinations demonstrated no evidence of tumor recurrence and subsequent chest CT revealed no signs of metastasis. Conclusion: Primary AM or AMCa of the skull is increasingly being described in the literature, but detailed reports on the malignant transformation of primary AM of the skull are lacking. The pathogenesis of this condition remains unclear. Aggressive treatment and close follow-up may be crucial for preventing disease recurrence and malignant transformation.

Intraoral Basal Cell Carcinoma of Soft Palate: A Diagnostic Dilemma and Review of Literature.

Basal cell carcinoma is the most common cancer worldwide. Most of basal cell carcinoma can be detected in the early stages and are generally well controlled with local resection. Despite the high incidence of BCC, intramucosal BCC is a very rare clinical entity. We hereby present a rare case report of pigmented BCC on soft palate and review the literature of this entity.

A Retrospective Analysis of 129 Ameloblastoma Cases: Clinical and Demographical Trends from a Single Institution.

Ameloblastomas are benign neoplasms of the jaw, but frequently require extensive surgery. The aim of the study was to analyze the demographic and clinicopathological features of ameloblastoma cases at a single Oral and Maxillofacial Surgery group in the United States. STUDY DESIGN: A retrospective chart review of patients evaluated for ameloblastoma between 2010 and 2020 at a single tertiary care center. Age, race, sex, tumor size, tumor location, and histological subtypes were recorded. RESULTS: A total of 129 cases of ameloblastoma were recorded with a mean patient age of 42 ± 18.6 years (range 9-91 years old), male to female ratio 1.08:1. Ameloblastoma presenting in the mandible outnumbered maxilla in primary (118 to 8, respectively) and recurrent cases (8 to 1, respectively). There was a higher prevalence of ameloblastoma in Black patients (61.3%) with mean age of Black patients occurring at 40.5 years and the mean age of White patients occurring at 47.8 years and mean tumor size trended larger in the Black patients (15.7 cm2) compared to White patients (11.8 cm2). CONCLUSION: Data suggests a strong influence of racial factors on the incidence of ameloblastoma, with regards to size, Black patients with ameloblastoma trended higher and more data is needed to clearly elucidate any relationship between the tumor size and race, as other factors may influence the size (such as time to discovery).

Desmoplastic histological subtype of ameloblastoma in 16 dogs.

Ameloblastoma in dogs most often has a highly conserved acanthomatous cell morphology and is recognized as canine acanthomatous ameloblastoma (CAA) while conventional ameloblastoma (CA) makes up a smaller yet morphologically diverse group of epithelial odontogenic tumors. In humans, a rare desmoplastic histological subtype has distinctive clinical, radiological, and microscopic features. Desmoplastic ameloblastoma (DA) has not previously been described in dogs, although it has been rarely referenced in the veterinary literature. This is the first thorough description of a case series of DA in dogs and describes clinical presentation, diagnostic imaging findings, histopathological features for diagnosis, and treatment outcome. Clinically, DA most often presents as a mass or swelling in the rostral mandible or maxilla of middle age to older dogs. On diagnostic imaging, the lesion has a radiolucent or mixed pattern with well-defined borders and variable loculation. As a solid, fibrous tumor with obscured odontogenic epithelium, DA is challenging to diagnose histologically and can mimic several other oral tumors, both benign and malignant. As an ameloblastoma, the biological behavior of DA is locally destructive yet benign and prognosis is favorable following surgical excision.

Application of machine learning in the preoperative radiomic diagnosis of ameloblastoma and odontogenic keratocyst based on cone-beam CT.

OBJECTIVES: Preoperative diagnosis of oral ameloblastoma (AME) and odontogenic keratocyst (OKC) has been a challenge in dentistry. This study uses radiomics approaches and machine learning (ML) algorithms to characterize cone beam computed tomography (CBCT) image features for the preoperative differential diagnosis of AME and OKC and compares ML algorithms to expert radiologists to validate performance. METHODS: We retrospectively collected the data of 326 patients with AME and OKC, where all diagnoses were confirmed by histopathologic tests. A total of 348 features were selected to train six ML models for differential diagnosis by a five-fold cross-validation. We then compared the performance of ML-based diagnoses to those of radiologists. RESULTS: Among the six ML models, XGBoost was effective in distinguishing AME and OKC in CBCT images, with its classification performance outperforming the other models. The mean precision, recall, accuracy, F1-score, and area under the curve (AUC) were 0.900, 0.807, 0.843, 0.841, and 0.872, respectively. Compared to the diagnostics by radiologists, ML-based radiomic diagnostics performed better. CONCLUSIONS: Radiomic-based ML algorithms allow CBCT images of AME and OKC to be distinguished accurately, facilitating the preoperative differential diagnosis of AME and OKC. ADVANCES IN KNOWLEDGE: ML and radiomic approaches with high-resolution CBCT images provide new insights into the differential diagnosis of AME and OKC.

Molecular pathogenesis of ameloblastoma.

Ameloblastoma (AM) is a benign, although aggressive, epithelial odontogenic tumour originating from tooth-forming tissues or remnants. Its aetiopathogenesis remains unclear; however, molecular analysis techniques have allowed researchers to progress in understanding its genetic basis. The high frequency of BRAF p.V600E as a main driver mutation in AM is well established; nevertheless, it is insufficient to explain its tumourigenesis. In this review, we aimed to integrate the current knowledge about the biology of AM and to describe the main genetic alterations reported, focusing on the findings of large-scale sequencing and gene expression profiling techniques. Current evidence shows that besides BRAF mutation and activation of the MAPK pathway, alterations in Hedgehog and Wnt/ß-catenin pathway-related genes are also involved in AM pathogenesis. Recently, a tumour suppressor gene, KMT2D, has been reported as mutated by different research groups. The biological impact of these mutations in the pathogenesis of AM has yet to be elucidated. Further studies are needed to clarify the impact of these findings in the identification of novel biomarkers that could be useful for diagnosing, classifying, and molecular targeting this neoplasm.

Adenomatoid odontogenic tumor: A histopathologic profile of 43 cases with evidence supporting a mixed odontogenic origin.

BACKGROUND: Adenomatoid Odontogenic Tumor (AOT) accounts for 3% of all odontogenic tumors. It has been classified by WHO as an odontogenic tumor of purely epithelial origin. The current study attempts to establish the origin of the tumor along with detailed histopathological and clinicoradiographic analysis of 43 cases of AOT. MATERIAL AND METHODS: Forty-three cases were reviewed from the departmental archives for demographic data, radiographic features and histological features. Further, histopathological slides were stained with Picrosirius Red (PSR) and observed under polarised light. RESULTS: A majority of the cases were seen in the anterior jaws (76.7%), and were less than 3 cms (76.7%) in greatest dimension. Equal number of cases were of follicular and extra-follicular location while one was peripheral. Predominantly solid histological pattern was noted in 53.5%. Varied sub-patterns were observed with most cases exhibiting solid nodules and strands of tumor cells. Few cases showed melanin pigmentation. Over a third of cases (37.2%) showed dentigerous cyst like areas and one case each showed features of ossifying fibroma and focal cemento-osseous dysplasia. Tumor droplets, hyaline rings within duct-like structures, dentinoid material and osteodentin showed reddish yellow birefringence when observed under polarised microscopy post PSR staining. CONCLUSION: This study highlights the diverse histopathological variation of AOT with evidence to reclassify it as a mixed odontogenic tumor based on the polarising microscopic findings with PSR staining.

Calcifying Odontogenic Cyst Demonstrates Recurrent WNT Pathway Mutations and So-Called Adenoid Ameloblastoma-Like Histology: Evidence Supporting Its Classification as a Neoplasm.

Calcifying odontogenic cyst (COC), once called calcifying cystic odontogenic tumor, is classified under the category of odontogenic cysts. However, the proliferative capacity of the lesional epithelium and consistent nuclear ß-catenin expression raise questions about its current classification. This study aimed to determine whether COC would be better classified as a neoplasm in the histologic and molecular context. Eleven odontogenic lesions diagnosed as COC or calcifying cystic odontogenic tumor were included in this study. The growth patterns of the lesional epithelium were analyzed histologically in all cases. ß-catenin immunohistochemistry and molecular profiling using Sanger sequencing and whole-exome sequencing were performed in 10 cases. Of the 11 cases studied, histologic features reminiscent of so-called adenoid ameloblastoma were observed in 72.7% (8/11), and small islands of clear cells extended into the wall in 36.4% (4/11). Intraluminal and/or mural epithelial proliferation was found in 72.7% of the cases (8/11). Nuclear ß-catenin expression was observed focally in all 10 cases studied, mainly highlighting epithelial cells forming morules and adjacent to dentinoid. CTNNB1 hotspot mutations were detected in 60.0% of the cases (6/10). All the remaining cases had frameshift mutations in tumor-suppressor genes involved in the WNT pathway, including APC and NEDD4L. Recurrent WNT pathway mutations leading to nuclear translocation of ß-catenin and distinct epithelial growth patterns found in COC are the neoplastic features shared by its solid counterpart, dentinogenic ghost cell tumor, supporting its classification as a tumor rather than a cyst.

An Unusual Case Report of Unicystic Ameloblastoma of the Mandible.

There are plenty of benign lesions that can result in swelling of the mandible, and these can be classified as odontogenic and non-odontogenic lesions. Among the categories of odontogenic lesion, ameloblastoma is the most occurring lesion that takes origin from the epithelial cellular elements and dental tissues in their different stages of development. Ameloblastoma is the most serious odontogenic neoplasm due to its prevalence and clinical characteristics. Ameloblastoma is a broad class which encompasses 80% of solid multicystic type of ameloblastoma with unicystic ameloblastoma (UA) variant included as vital clinicopathological form claiming the rest 20% along with peripheral ameloblastoma variant. UA refers to cystic lesions that seem like jaw cysts clinically, radiographically, or grossly but are lined by typical ameloblastomatous epithelium, with or without luminal and/or mural tumor development, on histologic investigation. Around 5-15% of all ameloblastic lesions do not have a propensity to metastasis, and this is UA. Unicystic mural form, although slow growing overall, is very invasive locally and has a high recurrence rate. As UA tumors show very close features with dentigerous cyst, a very sharp differential diagnosis protocol need to be executed to exclude the other unicystic odontogenic lesions considering the clinical, radiological, and biological characteristics along with proper follow-up and seeing any recurrence of the lesion taking place. Here, we report the case of a twenty-one year male patient with UA of the mandible and review of the literature.

The 'D-M-C' strategy for conventional ameloblastoma of the mandible: a retrospective study.

The purpose of this multicentre study was to evaluate the efficacy of the 'dredging-marsupialization-curettage' (D-M-C) strategy in the treatment of conventional intraosseous ameloblastoma of the mandible. A total of 31 patients from three institutions, who had a pathological diagnosis of conventional ameloblastoma of the mandible, were treated with the D-M-C strategy. The surgical protocol comprised a dredging and marsupialization (D-M) step, with additional D-M steps as required. The patients then underwent curettage (C) once an obvious effect of the D-M step had been achieved during follow-up. Eight patients were followed up for ≥36 months but <60 months, while 23 were followed up for ≥60 months. Nineteen of the 23 patients followed up for ≥60 months were disease-free at the last follow-up, with no evidence of recurrence. The D-M step is effective for reducing the tumour size and preserving vital structures. The D-M-C surgical strategy may be a feasible treatment option for conventional ameloblastoma of the mandible.

Proteomics study of bone tissue around ameloblastoma and the potential mechanism of CD36 in bone remodelling.

Ameloblastoma (AM) is characterised by local aggressiveness and bone resorption. To our knowledge, the proteomic profile of bone adjacent to AM has not previously been explored. We therefore looked at the differential proteins in cancellous bone (CB) adjacent to AM and normal CB from the mandible. CB proteins were extracted, purified, quantified, and analysed by liquid chromatography-mass spectrometry (LC-MS) using samples from five patients with AM. These proteins were further investigated using gene ontology for additional functional annotation and enrichment. Proteins that met the screening requirements of expression difference ploidy > 1.5-fold (upregulation and downregulation) and p < 0.05 were subsequently deemed differential proteins. Immunohistochemical staining was performed to confirm the above findings. Compared with normal mandibular CB, 151 differential proteins were identified in CB adjacent to the mandibular AM. These were mainly linked to cellular catabolic processes, lipid metabolism, and fatty acids (FA) metabolism. LC-MS and immunohistochemistry showed that CD36 was one of the notably decreased proteins in CB bordering the AM compared with normal mandibular CB (p = 0.0066 and p = 0.0095, respectively). CD36 expression in CB correlates with bone remodelling in AM, making CD36 a viable target for therapeutic approaches.

Collision Tumour Comprising Desmoplastic Ameloblastoma and Squamous Odontogenic Tumour in the Anterior Maxilla: A Case Report.

Collision tumours, characterized by the simultaneous occurrence of two distinct neoplasms within the same anatomical site, are exceedingly rare in oral pathology. This case report presents an uncommon collision tumour involving desmoplastic ameloblastoma and squamous odontogenic tumour in the anterior maxilla of a 52-year-old male from the Indian population. Desmoplastic ameloblastoma is a variant of ameloblastoma known for its unique histopathological features, while squamous odontogenic tumour is a benign epithelial odontogenic tumour with distinctive clinical behaviour. The rarity of this occurrence emphasizes the need for accurate diagnosis and effective treatment strategies. This report discusses the clinical presentation, radiographic findings, and histopathological characteristics of this collision tumour. Through the presentation of this case, we aim to contribute to the understanding of these rare entities and their management considerations.

Metamorphosis of Dentigerous cyst: A case Series with Insight into Molecular Profiling.

The objective of this study was to review the clinical, radiologic, and histologic aspects of cases of dentigerous cysts metamorphosing into different entities along with comments on the molecular factors involved in the process. A series comprising 8 cases of dentigerous cysts was performed retrospectively along with a comprehensive literature review. Two cases of dentigerous cyst converting into mucous metaplasia were included, out of which one case was transformed into ameloblastoma after a year. The other two cases were reported as acanthomatous and unicystic ameloblastoma, whereas four transitioned to AOT. The complete review of cases and literature with molecular profiling concluded that the lining of dentigerous cysts has the potential for transforming into benign odontogenic tumors. Therefore, a careful clinical and histopathological examination is crucial for the correct diagnosis. Also, a thorough molecular understanding of the cystic lining is required.

BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis.

BACKGROUND: Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas. METHODS: This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%. RESULTS: Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment. CONCLUSION: BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.

Maxillary Ameloblastoma with Local Recurrence, Orbital Invasion, and Systemic Metastases: A Case Report and Review of the Literature.

Introduction: Maxillary ameloblastoma is a rare, slow-growing odontogenic tumor that can recur after surgical excision, be locally aggressive, and rarely develop systemic metastases. We describe the course and management of a patient with recurrent maxillary ameloblastoma with orbital invasion and systemic metastases, the fourth case of its kind to be described in the literature. Case Presentation: A 50-year-old female presented with left hyperglobus. A diagnosis of maxillary ameloblastoma was made based on biopsy and neuroimaging with MRI and CT. Surgical management included partial maxillectomy with orbital floor reconstruction, given the orbital invasion. Three years later, left hyperglobus recurred, and the patient was found to have orbital recurrence and lung metastases on PET imaging. The lung and orbital lesions have responded well to chemoradiation therapy without surgical intervention. Conclusion: Maxillary ameloblastoma is a rare tumor that typically arises from odontogenic tissues. Though considered benign, they can recur and in the case of our patient, metastasize. Complete surgical excision with wide surgical margins is associated with a shorter average time to recurrence and a lower incidence of metastasis. Cases of metastasis are managed with chemotherapy with or without adjuvant radiotherapy. Precision medicine may play a role in managing this entity in the future, given the discovery of differing profiles of maxillary ameloblastoma compared to mandibular. Ophthalmologists should be aware of this tumor as it can invade the orbit, resulting in significant ocular morbidity and mortality.

Virtual Surgical Planning in Condyle Reconstruction of Posterior Mandibulectomy Defects.

Background: Ameloblastoma is a rare odontogenic tumor most commonly located within the mandible. These tumors can grow to massive proportions and result in malocclusion. Segmental mandibulectomy and reconstruction with an osteocutaneous free flap are frequently required. Virtual surgical planning (VSP) aids the surgeon in creating precise anatomic reconstruction when there is preoperative malocclusion due to tumor size. In this study we seek to further examine reconstruction of posterior mandibulectomy defects inclusive of condylar resection. Methods: Retrospective review of patients treated for giant ameloblastoma (tumor >4 cm) was examined; 3 patients with posterior tumors requiring ramus and condylar resection were included. Reconstruction in all patients was performed using fibula free flaps and VSP custom-made mandibular reconstruction plates. In these patients the reconstructed ramus was shortened and precise contouring done with a burr to recreate the native condylar surface. Intermaxillary fixation was used to maintain occlusion for 1 month postoperatively. Inferior alveolar nerve repair with allograft and nerve connectors was performed for all 3 patients. Results: All patients underwent successful mandibular reconstruction with preservation of mandibular function and improved occlusion postoperatively. Inferior alveolar nerve repair using nerve allograft allowed for neurosensory recovery in the mandibular division of trigeminal nerve distribution in 2 of the 3 patients. Conclusions: Giant ameloblastoma involving the mandibular condyle can be successfully treated with the fibula free flap utilizing mandible reconstruction plates and VSP. This technique allows for excellent restoration of occlusion and neurosensory recovery when paired with reconstruction of the inferior alveolar nerve at time of reconstruction.