Ameloblastoma Research Articles (Page 1)

Background: Ameloblastoma (AM) and odontogenic keratocyst (OKC) are benign intraosseous lesions with similar radiographic features but distinct clinical behaviors and treatment approaches. Their differentiation through imaging remains challenging due to overlapping anatomical presentations and the absence of well-defined diagnostic criteria. In this context, artificial intelligence—particularly Convolutional Neural Networks (CNNs)—emerges as a promising tool for enhancing diagnostic accuracy. Methods: An integrative literature review was conducted using PubMed/Medline and Scopus databases, covering studies from 2018 to 2023. The search included the descriptors "Ameloblastoma," "Odontogenic Keratocyst," "Odontogenic Cysts," "Convolutional Neural Network," "Artificial Intelligence," and "Deep Learning." Results: Eleven studies met the inclusion criteria. CNNs achieved diagnostic accuracy ranging from 70% to 99.25%, with sensitivity from 71% to 98.08% and specificity up to 100%. Studies using CT imaging generally outperformed those using panoramic radiographs. However, most models relied exclusively on imaging data, and lesion-specific performance metrics were often underreported. Methodological inconsistencies—such as limited dataset diversity and overreliance on accuracy alone—were also observed. Conclusion: CNNs show strong potential as complementary tools in the differential diagnosis of AM and OKC, particularly when applied to high-resolution imaging modalities. Nonetheless, their clinical applicability remains limited by the lack of stratified performance data, inconsistent reporting standards, and the absence of multimodal integration. Future research should emphasize external validation, multicenter datasets, and the combination of imaging with clinical and histopathological features to improve real-world diagnostic performance.

Pro-apoptotic effects of 5-fluorouracil on ameloblastoma in vitro: Exploring the potential of topical 5-FU ointment in adjunctive therapy.

Ameloblastoma (AB) are aggressive odontogenic tumors, often treated with wide marginal resection and concurrent reconstruction. Extended total temporomandibular joint replacement (eTMJR) prosthesis is a viable treatment option for reconstruction of large defects caused by resection of AB tumors. The objective of this study was to systematically review the utilization and effectiveness of eTMJR prosthesis in treating patients with AB tumors. A detail search in Web of Science, Medline/PubMed, Google Scholar and Embase identified studies reporting AB patients who underwent implantation of eTMJR prosthesis. Studies reporting the use of eTMJR prosthesis in the management of AB tumors were eligible, with no restriction of the study type, language or year of publication and patient's demographics. Quality assessment of the selected case reports and case series was carried out with the 13 Domains (30 Items) of the CARE checklist, using a scoring scale of "0" (No/ non-adherence), "1" (Yes/ adherence) and "2" (unclear). The completeness of reporting (COR) score was determined as the ratio of "yes" responses to "total" (i.e., yes + no + unclear) responses. A total of 27 studies were selected for analysis, including 15 case reports, 06 case series and 06 retrospective cohort studies. These studies presented 41 patients of AB who received eTMJR prosthesis. The patients' mean age was 37.8 ± 14.9 (range: 14-72, median: 36) years, whereas the mean follow-up period was 19.7 ± 20.3 (range: 1-84, median 12) months. The majority of studies did not document all clinically relevant data regarding patient clinical presentation, surgical procedures, long-term follow-up and post-operative complications. The mean ± SD (range, median) COR score for all case reports/ series was 61.7 ± 23.5 (4.0-100, 64.0) %. The use of eTMJR prosthesis in the management of AB tumors has demonstrated promising treatment outcome in case reports/ series. However, large cohort randomized controlled trials are essential to establish their therapeutic efficacy.

Tenascin-C Expression in Relation to Tumor-Stroma Interaction in Ameloblastoma.

Ameloblastoma (AM) is a well-known benign odontogenic tumor recognized for its aggressive nature, believed to originate from tooth-forming tissue or the dental follicle (DF). Phosphoproteins are crucial for cellular signaling, enabling intracellular communication and regulating various physiological processes. In cancer, phosphoproteins are fundamental to both pathogenesis and pathophysiology. However, studies on phosphoproteins in AM are still limited. This study aimed to compare phosphoprotein profile and identify the crucial phosphoproteins between AM and DF. The phosphoprotein profiles of seven AM and five DF were discovered using mass spectrometry, and their associated phosphosites were examined by Netphos 3.1. Biological functions were analyzed by Metascape database. Thirteen significant phosphoproteins were found in AM, and six in DF, all of which have phosphorylation sites. For example, among the proteins uniquely identified in AM were SENP1 (Sentrin-specific protease 1), DDX42 (ATP-dependent RNA helicase DDX42), LMBR1L (Protein LMBR1L), Cathepsin H (CATH), and Retinoblastoma-binding protein 5 (RBBP5), whereas those unique to DF included GC-rich sequence DNA-binding factor (GCF), Plexin-C1 (PLXC1), and proline/serine-rich coiled-coil protein 1 (PSRC1), PTHD3 (Patched domain-containing protein 3), and TPC6B (Trafficking protein particle complex subunit 6B). For biological analysis, the enriched terms included processing of capped intron-containing pre-mRNA, signaling by rho GTPases, establishment of organelle localization, signaling by receptor tyrosine kinases and cell morphogenesis. These phosphoproteomic findings provide essential insights into the pathogenesis of AM and warrant further investigation. This is crucial for advancing our understanding of AM biology and identifying potential therapeutic targets.

Ameloblastoma is a benign but locally aggressive odontogenic tumour broadly divided into conventional, unicystic, peripheral, adenoid and metastasising types. The first three entities compose the majority and especially the conventional type which has different histopathological subtypes such as follicular, plexiform, acanthomatous, granular cell, basal cell and desmoplastic have been described. We report the largest series of ameloblastoma in a single study to analyse the demographic characteristics according to histopathological subtypes of ameloblastoma. 1,312 cases of ameloblastoma reported from two centres in Sri Lanka and Malaysia were analysed according to age, site and histopathological subtype. Of the total of 1,312 cases, the mean age for conventional ameloblastoma (excluding desmolastic subtype) was 36.82±16.57. It was 46.3±15.21 for categorisewhile peripheral and unicystic ameloblastoma occurred at 40.77±16.35 and 31.00±17.37, respectively. Ninety percent of the cases were in the mandible (p=0.00001) with significant predilection for the right side. Unicystic and plexiform subtypes were mostly seen in the 11-20 age group while the desmoplastic subtype was seen in the 51-60 age group. The commonesthistological subtype was follicular subtype and acanthomatous changes were observed predominately in combination with follicular subtype. Majority of the acanthomatous subtype was observed inposterior mandible (p=0.00001). The frequency of luminal (243) and mural (246) subtypes werealmost similar. This study provides a comprehensive demographic detail of differenthistological subtypes of ameloblastoma using the largest sample in the literature. The present findingswill be helpful in classification and understanding of different subtypes of the tumours.

The study aimed to evaluate the significant trends of advancement in the body of literature of specialty journals on molecular biological investigations of ameloblastoma (AB). Additionally, this bibliometric study sought to identify the authors, organizations, journals, and countries from emerging regions that have exerted the most significant influence on molecular biological and bioinformatics studies on AB. The novelty of this study lies in its comprehensive bibliometric integration of bioinformatics and molecular perspectives, offering a structured roadmap for future ameloblastoma research. A complete list of AB molecular biological research citations was found in Scopus. The search was restricted to papers published between 2014 and 2024, but there were no restrictions on the language or type of research studies. The study examined total citations, citation density, journal name, impact factor, journal category, quartile, published year, authors, affiliations, and study type. The analysis included collecting 112 publications published between 2014 and 2024. There were 95 original research papers, 6 systematic reviews, 5 case reports, 3 brief communications, and 6 systematic reviews and meta-analyses. Our analysis identifies noteworthy authors and nations that have contributed, with Brazil emerging as a leading figure in this field of study. The research on AB, especially its biological profile, has changed significantly across the years, as can be observed by perusing the contents of the papers included here. The data from this study would help the researchers target specific objectives for future research in more relevant avenues.

Ameloblastoma (AM) is a clinically significant odontogenic tumour known for its local invasive and high post-treatment recurrence risk. Despite advancements in surgical techniques, predicting recurrence remains challenging. The role of immunomarkers in predicting recurrence of ameloblastoma remains non-conclusive. The aim of this study is to investigate the predictability of recurrence using selected immune markers. 42 AM samples comprising 16 non-recurrent AM (AMNR), 13 primary tumour of recurrent AM (PAMR), and 13 recurrent AM from the same patient as PAMR (RAM) were immunohistochemically examined for the expression of interleukin 1-alpha (IL-1α), interleukin 6 (IL-6) and CD 10. Immunoreactive scoring (IRS) was used to assess the expression levels. The expression levels were further analyzed for the correlation with demographic and clinicopathological parameters of interest. The three markers were heterogeneously expressed in the ameloblastoma samples (IL-1α = 97.6%; IL-6 = 97.6% and CD 10 = 90.5%). Major findings were the upregulation of IL-6 (RAM > PAMR > AMNR) in RAM, while IL-1α and CD 10 scored higher in AMNR (AMNR > PAMR > RAM). Further correlation with clinicopathological parameters showed significant association between IL-1α expression with histopathological variants in AMNR (p = 0.03) and PAMR (p = 0.002). IL-6 expression was significantly correlated with tumour locality in AMNR (p = 0.01), and CD 10 showed significant correlation with tumour locality in PAMR (p = 0.02) and subsites of tumour locality in PAMR (p = 0.005) and RAM (p = 0.002). The upregulation of IL-6 in recurrent ameloblastoma may predict its potential for recurrence. However, this interpretation should be considered tentative due to the inherent limitations of the study. Immunoexpression of IL-1α and CD 10 requires further investigation to elucidate their roles in tumourigenesis and invasiveness of ameloblastoma.

The clinical classification of ameloblastoma (AM) plays a decisive role in the selection of treatment options, but the difference of single-cell landscape among clinical classifications is still unclear. At the same time, there is an urgent need to understand the key cell subtypes that determine the clinical subtypes. We characterized the single-cell transcriptional profiles of clinical subtypes of AM. We also characterized a pseudotime transition trajectory from immunoactive epithelial cells to vascular-associated fibroblasts, identifying key transcription factors involved in this process. Notably, we observed significant heterogeneity between M1 and M2 macrophages among the clinical subtypes of AM. Furthermore, our analysis revealed that metabolic disorder in AM was primarily driven by the metabolic disturbances in M1 and M2 macrophages. At the cellular communication level, we highlighted the role of M2 macrophages in mediating cell interactions, focusing on the RANKL/RANK pathway associated with osteoclast activity. Finally, we attempted to establish a unicystic AM–derived epithelial cell line and utilized it to construct an AM-like organoid model; we found that M2 macrophages competed with AM for L-cysteine to achieve cystic changes in the solid lesion. Our exploration of pathogenesis underlying various clinical types of AM advances our knowledge of AM heterogeneity, offering promising targets for novel therapeutic strategies.

The existence of intraoral basal cell carcinoma (IOBCC) remains controversial, despite reported cases in the literature. A systematic search of four electronic databases and grey literature was conducted. Strict inclusion criteria were established to define a true case of IOBCC, including Ber-EP4 positivity to distinguish it from peripheral ameloblastoma and the absence of a history of skin lesions-either nearby, which could indicate direct infiltration, or at distant sites, which could suggest metastasis rather than a true primary IOBCC. A total of 9 cases met the inclusion criteria. IOBCC lesions were located on the palate, buccal mucosa and gingiva, with no cases involving the tongue or floor of the mouth-common sites for squamous cell carcinoma. Histologically, islands of basaloid cells with peripheral palisading and stromal retraction were the predominant findings. All cases were Ber-EP4 positive. Six patients remained disease-free during follow-up, one experienced multiple recurrences, and two had no follow-up data. IOBCC is extremely rare, with few documented cases. While previous studies suggested the gingiva as a common site, this review found no clear predilection, and some previously reported cases may have been misdiagnosed as peripheral ameloblastoma. Ber-EP4 positivity in IHC is valuable for distinguishing between these entities. Additionally, by excluding cases with potential infiltration from skin lesions, this review underscores the importance of a thorough dermatological evaluation to rule out cutaneous extension or metastasis.

Ameloblastoma (ABL), a common odontogenic tumor in the maxillofacial region, presents primarily as unicystic (U-ABL) and conventional (C-ABL) variants. Despite shared epithelial features, their distinct biological behaviors may stem from interactions between connective tissue and epithelial cells. Vimentin 3 (VIM3), a truncated variant of Vimentin-Full Length (VIMFL), exhibits unique biological properties. This study is the first to investigate VIM3 expression in ABLs. Formalin-fixed paraffin-embedded (FFPE) samples of C-ABL (n = 30), U-ABL (n = 30), and dental follicles (DF, n = 30) were analyzed. Immunohistochemical evaluation of VIM3, VIMFL, WNT5a, and MTCO1 was performed, alongside qRT-PCR for VIM3, VIMFL, WNT5a, ROR2, and miR-498. VIM3 expression was significantly higher in C-ABL (p < 0.0001) compared to U-ABL and DFs. VIMFL was absent in the epithelial components of all cases. C-ABL showed significantly higher WNT5a (p < 0.0001) and MTCO1 (p = 0.0327) expression. qRT-PCR revealed significant differences in VIM3 and miR-498 levels between U-ABL and DFs (p < 0.0001). No significant differences were found for WNT5a, VIMFL, or ROR2 (p > 0.05). This study identifies VIM3 expression in ABLs, distinct from VIMFL, suggesting its potential as a biomarker. Additionally, mitochondrial dysfunction may play a role in ABL tumorigenesis.

THE MANAGEMENT OF TEETH IN ODONTOGENIC KERATOCYST AND AMELOBLASTOMA AND ITS PROGNOSTIC ROLE IN RECURRENCE: A SYSTEMATIC REVIEW AND META-ANALYSIS WITH TRIAL SEQUENTIAL ANALYSIS.

Peripheral Ameloblastoma, Rare and Often Misdiagnosed Entity. Case Report and Review of Literature

ABSTRACTIntroduction:Odontogenic tumors are lesions that originate from the tooth-producing tissues or their remnants that remain entrapped either within the jawbones or into the adjacent soft tissues. They comprise a range of disorders of growth, from malignant and benign neoplasms, to malformations of dental tissues of self-limited growth.Aim:To do a retrospective analysis of 56 cases of odontogenic tumors in oral cavity over a period of 5 years.Materials and Methods:Institutional histopathology registry was scrutinized to gather data of cases of odontogenic tumors over a period of 5 years (2020-2024). The information of all the cases was thoroughly reviewed, analyzed, and tabulated.Results:A total of 56 cases of odontogenic tumors were found. Males were most commonly affected than females (M > F). The most common site was posterior mandible (molar-ramus) region. We found 19 cases of solid multicystic ameloblastoma (SMA), 22 cases of unicystic ameloblastoma, 5 cases of KCOT, 3 cases each of desmoplastic ameloblastoma and AOT, and 2 each of peripheral ameloblastoma and ameloblastic carcinoma.Conclusion:Ameloblastoma was the commonest odontogenic tumor with unicystic variant being 39.28% followed by SMA (33.92%), KCOT (8.92%), AOT (5.35%), and desmoplastic variant (5.35%).

To identify risk factors for the recurrence of conventional ameloblastoma (AM) and develop a predictive nomogram model for postoperative recurrence. Clinical, pathological, and radiographic data from 235 patients treated at the Hospital of Stomatology, Sun Yat-sen University (2005-2022) were retrospectively analyzed. Logistic regression identified independent prognostic factors, and a nomogram model was constructed using R software. Multilocularity, cortical bone perforation, and inferior alveolar nerve involvement significantly increased recurrence risk in conventional AM (p < 0.05). Logistic regression analysis revealed that multilocular tumors (OR = 3.68, p = 0.002), honeycomb patterns (OR = 10.80, p < 0.001), and cortical bone perforation (OR = 2.62, p = 0.011) were significantly associated with increased recurrence risk. Surgical approaches significantly impacted recurrence rates, with curative resection surgery (CRS) resulting in the lowest recurrence risk as compared with fenestration decompression (FD) and local curettage (LC). CRS and curettage and fenestration decompression (CFD) were identified as effective protective factors against recurrence (p < 0.001). A nomogram model with high predictive accuracy (AUC = 0.867) was developed. Multilocularity, cortical bone perforation, and inferior alveolar nerve involvement significantly increased the risk of recurrence. The nomogram model provided effective risk assessment for clinical decision-making.

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT+-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT+-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.

Ameloblastoma (ABM) is an aggressive, localized, infiltrating epithelial odontogenic neoplasm. The molecular pathogenesis of ABM is unknown, and studying its metabolic profile may allow the identification of biomarkers relevant to the diagnosis and prediction of pathology. Metabolomic analysis of 41 serum samples from 21 ABM patients and 20 healthy controls (HCs) was performed using gas chromatography-mass spectrometry (GC-MS). Using LASSO regression and receiver operating characteristic analysis, biomarker metabolites were screened and validated, and a diagnostic model was established. Tissue samples from ABM patients were analyzed using BRAF V600E-specific immunohistochemistry to investigate the impact of the BRAF V600E mutation on metabolic reprogramming in ABM. A total of 73 metabolites were identified in the samples. The ABM had a total of 32 dysregulated metabolites, of which 30 were downregulated. A diagnostic panel of 10 metabolites was then generated. The panel accurately identified ABM with 100% sensitivity, 100% specificity, and an AUC of 1.00. In addition, the presence of the BRAF-V600E mutation in ABM is associated with increased serum glutamine levels. This study identified distinct metabolic characteristics of ABM and established a diagnostic model. Our research also shows that BRAF-V600E may contribute to metabolic alterations in ABM.

B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation stands as a pivotal genetic alteration strongly associated with several neoplasms and contributes significantly to their pathogenesis as well as potential targeted treatment strategies. This cross-sectional study aimed to determine the frequency of BRAF V600E mutation in ameloblastoma in a multi-center of Thailand. Anti-BRAF V600E (clone VE1) immunohistochemistry was performed on 227 conventional ameloblastoma (AM) and 113 unicystic ameloblastoma (UA) samples collected from four major dental schools located in the Central, North, South, and Northeast regions of Thailand. Tumor cells from randomly chosen AM cases were also micro-dissected from the FFPE sections and subjected to DNA sequencing to confirm the immunohistochemical results. BRAF V600E mutation was detected in 71.8% of the AM samples, while 65.5% of samples with UAs demonstrated BRAF V600E positivity. The BRAF V600E mutation was significantly different in the histological subtypes of AMs in the four centers (p = 0.012) and the location of UA in three centers (p = 0.013). There was no significant association between the BRAF V600E mutation and the location of ameloblastoma in the overall prevalence of our multi-center study; nonetheless, a statistically significant association was found between the BRAF V600E mutation and the mandible location of AMs from the Central Faculty of Dentistry, Mahidol University (MU) center (p = 0.033), as well as with the histological subtypes of AMs from the Southern Faculty of Dentistry, Prince of Songkla University (PSU) center (p = 0.009). No statistical association was observed between the BRAF V600E mutation and AM and UA recurrence (p = 0.920 and p = 0.312), respectively. The results of DNA sequencing performed in randomly selected 40 BRAF V600E-positive and 20 BRAF V600E-negative ameloblastoma tissues were in accordance with the immunohistochemical findings. As a result of a notable prevalence of BRAF V600E in Thai individuals diagnosed with ameloblastoma, they may benefit from the utilization of adjunctive anti-BRAF targeted therapy for treatment.

The aim of this study was to develop a radiomics model based on cone beam CT (CBCT) to differentiate odontogenic cysts (OCs), odontogenic keratocysts (OKCs), and ameloblastomas (ABs). In this retrospective study, CBCT images were collected from 300 patients diagnosed with OC, OKC, and AB who underwent histopathological diagnosis. These patients were randomly divided into training (70%) and test (30%) cohorts. Radiomics features were extracted from the images, and the optimal features were incorporated into random forest model, support vector classifier (SVC) model, logistic regression model, and a soft VotingClassifier based on the above 3 algorithms. The performance of the models was evaluated using a receiver operating characteristic (ROC) curve and the area under the curve (AUC). The optimal model among these was then used to establish the final radiomics prediction model, whose performance was evaluated using the sensitivity, accuracy, precision, specificity, and F1 score in both the training cohort and the test cohort. The 6 optimal radiomics features were incorporated into a soft VotingClassifier. Its performance was the best overall. The AUC values of the One-vs-Rest (OvR) multi-classification strategy were AB-vs-Rest 0.963; OKC-vs-Rest 0.928; OC-vs-Rest 0.919 in the training cohort and AB-vs-Rest 0.814; OKC-vs-Rest 0.781; OC-vs-Rest 0.849 in the test cohort. The overall accuracy of the model in the training cohort was 0.757, and in the test cohort was 0.711. The VotingClassifier model demonstrated the ability of the CBCT radiomics to distinguish the multiple types of diseases (OC, OKC, and AB) in the jaw and may have the potential to diagnose accurately under non-invasive conditions.

To investigate the prevalence of BRAF, SMO, KRAS, HRAS, NRAS, FGRF2, and CTNNB1 gene mutations in Chinese ameloblastoma (AM) patients and explore their associations with clinical characteristics. DNA was extracted from 89 formalin-fixed paraffin-embedded AM samples (9 unicystic and 80 conventional). PCR and Sanger sequencing were used to detect mutations, followed by statistical analysis to assess correlations between mutations and clinical variables. BRAF V600E mutations were significantly prevalent, occurring in 92% (59/64) of mandibular AMs compared to 40% (10/25) in maxillary AMs. SMO mutations were found in 20% (5/25) of maxillary and 3.1% (2/64) of mandibular AMs. FGFR2 mutations were detected in six maxillary and two mandibular AMs, while RAS mutations were present in four maxillary and one mandibular AM. No detectable HRAS, NRAS(G12), or CTNNB1 mutations were observed. BRAF mutations showed mutual exclusivity with SMO and FGFR2 mutations. The high prevalence of BRAF V600E mutations, particularly in mandibular AMs, suggests its potential as a diagnostic and therapeutic target. Distinct mutation profiles between maxillary and mandibular AMs indicate molecular diversity. In BRAF-negative cases, alternative oncogenic pathways involving SMO, FGFR2, and RAS may be actionable targets, underscoring the need for personalized treatment approaches.