Ameloblastoma Research Articles

Comparative transcriptional profiling of canine acanthomatous ameloblastoma and homology with human ameloblastoma

Ameloblastomas are odontogenic tumors that are rare in people but have a relatively high prevalence in dogs. Because canine acanthomatous ameloblastomas (CAA) have clinicopathologic and molecular features in common with human ameloblastomas (AM), spontaneous CAA can serve as a useful translational model of disease. However, the molecular basis of CAA and how it compares to AM are incompletely understood. In this study, we compared the global genomic expression profile of CAA with AM and evaluated its dental origin by using a bulk RNA-seq approach. For these studies, healthy gingiva and canine oral squamous cell carcinoma served as controls. We found that aberrant RAS signaling, and activation of the epithelial-to-mesenchymal transition cellular program are involved in the pathogenesis of CAA, and that CAA is enriched with genes known to be upregulated in AM including those expressed during the early stages of tooth development, suggesting a high level of molecular homology. These results support the model that domestic dogs with spontaneous CAA have potential for pre-clinical assessment of targeted therapeutic modalities against AM.

Comparative Evaluation of Polarization Colors of Collagen Fibers in Odontogenic Keratocyst and Ameloblastoma Using Picrosirius Red Stain (Histochemical Study)

Aims: studying the quality and quantity of collagen fibers may help to delineate their influence on the aggressiveness and growth potential of the OKC and ameloblastoma. The aims of this study were to evaluate and compare the polarization colors, orientation, and organization of collagen fibers in the connective tissues of the odontogenic keratocyst (OKC), and ameloblastoma (AB) using picrosirius red (PSR) stain under a polarizing microscope with correlation to their biologic behavior.
 Materials and method: polarization colors, orientation, and organization of collagen fibers in pre-diagnosed cases of OKC and AB, twenty each, and two control cases of dentigerous cyst (DC) were histochemically analyzed using PSR stain and a polarized light microscope.
 Results: comparing the collagen fibers in the two lesions, there was no significant difference with respect to the polarization colors, orientation, and organization.
 Conclusion: PSR staining and polarizing microscopy is a powerful tool to appraise the nature and arrangement of collagen fibers in odontogenic lesions. The connective tissue of OKC showed a predominance of green-yellow birefringence, and loosely packed fibers, this can be correlated to the aggressive nature of this lesion.

A comparative study of the expression of cyclin D1, COX-2, and KI-67 in odontogenic keratocyst vs. ameloblastoma vs. orthokeratinized odontogenic cyst

BackgroundOdontogenic keratocysts (OKCs) and orthokeratinized odontogenic Cysts (OOCs) are distinct clinicopathological entities. OKC appears to behave in a way more similar to that of a neoplasm, such as ameloblastoma (AB). The aim of this study is to compare the influence of Ki-67, Cyclin D1 and COX-2 in the diagnosis and pathogenesis of OKC, OOC and AB. Materials and methodsA cross-sectional observational study of 41 samples was organized into 3 groups: (1) OKC n=22; (2) AB n=13 and (3) OOC n=6. Paraffin blocks were sectioned and stained with hematoxylin and eosin (H&E). Immunohistochemical study using Bond Polymer Refine Red Detection Kit, Leica, Wetzlar, Germany, was performed for the following antibodies: Ki-67, Cyclin D1 and COX-2. Double blind immunostaining was quantified subjectively. Staining: nuclear or cytoplasmic; nuclear (Ki-67 and Cyclin D1>5% positive) and cytoplasmic (COX-2; 1; 1–30 cytoplasm: 2; 31–60 cytoplasm; 3; 61–100 cytoplasm). Considering positive stained 61-100 cytoplasms. ResultsThe expression of Ki-67 was higher in the OKC group than in the AB group (p<0.05). Cyclin D1 showed a higher expression in OKC vs. OOC and OKC vs. AB (p<0.05). Finally, expression of COX-2 was higher in OKC vs AB (p<0.05). ConclusionsCOX-2, Ki-67 and Cyclin D1 show statistically significant differences between the groups, suggesting that they could be useful tools in the differential diagnosis between OKCs and OOC and a predictive indicator for their biologic behaviour. The higher expressions of these 3 markers of OKC vs AB highlight once more the aggressive behaviour of this now re-considered cystic lesion. These markers could prove useful in the choice of more aggressive surgical treatment in OKCs as their behaviour appears to be similar to that of a neoplasm.

PLEXIFORM SCHWANNOMA INVOLVING THE ANTERIOR MANDIBLE

<h3>BACKGROUND</h3> Schwannomas and neurofibromas are common benign neoplasms originating from the peripheral nerves. These neoplasms originating in the oral and para-oral tissues, especially involving the jaw, are extremely rare. Plexiform schwannoma is a unique variant in which the Schwann cells demonstrate a unique plexiform pattern. A literature search revealed only 2 case reports of plexiform schwannoma involving the jaws. <h3>CASE REPORT</h3> A 47-year-old male patient was referred for consultation by his dentist for evaluation and diagnosis of a radiolucency in the anterior mandible with no apparent odontogenic/clinical etiology. The patient complained of sensitivity in this region and occasional radiating pain. Clinical examination showed no signs of infection or inflammation. The patient denied any known medical disease or history of surgeries. Cone beam computed tomography examination revealed a large, well-defined, hypodense, partially corticated lesion in the anterior mandible with evidence of impingement of the facial cortex, resulting in a scooped-out defect. The radiologic differential interpretation included peripheral ameloblastoma and peripheral giant cell granuloma. An incisional biopsy was recommended to determine the nature of this entity. Microscopic examination revealed a multicircumscribed, lobular mass bounded by a thin fibrous connective tissue capsule. Each lobule was composed of streaming fascicles of spindle-shaped cells, some of which formed a palisading arrangement. Immunohistochemistry was positive for protein S-100 and epithelial membrane antigen, which confirmed the diagnosis of plexiform schwannoma. <h3>DISCUSSION/CONCLUSIONS</h3> This is an unusual case of a unique variant of schwannoma, in this case a plexiform type, which is an extremely rare neurogenic neoplasm. This atypical presentation and location of the lesion, which mimics other peripheral benign neoplasms, highlights the importance of a systematic workup with the aid of the appropriate diagnostic tools for ideal patient care. It demonstrates the important role of immunohistochemistry to confirm the nature of this entity.

ING3 and ING4 immunoexpression and their relation to the development of benign odontogenic lesions.

The sample comprised of 20 odontogenic keratocysts (OKC), 20 ameloblastomas (AM), and 15 adenomatoid odontogenic tumors (AOT) specimens. Nuclear and cytoplasmic immunolabeling of ING3 and ING4 were semi-quantitatively evaluated in epithelial cells of the odontogenic lesions, according to the percentage of immunolabelled cells in each case. Descriptive and statistics analysis were computed, and the p-value was set at 0.05. No statistically significant differences were found in cytoplasmic and nuclear ING3 immunolabeling among the studied lesions. In contrast, AOTs presented higher cytoplasmic and nuclear ING4 labeling compared to AMs (cytoplasmic p-value = 0.01; nuclear p-value < 0.001) and OKCs (nuclear p-value = 0.007). ING3 and ING4 protein downregulation may play an important role in the initiation and progression of more aggressive odontogenic lesions, such as AMs and OKCs.

Expression of SOX2 and OCT4 in odontogenic cysts and tumors

BackgroundAberrant expression of stem cell markers has been observed in several types of neoplasms. This trait attributes to the acquired stem-like property of tumor cells and can impact patient prognosis. The objective of this study was to comparatively analyze the expression and significance of SOX2 and OCT4 in various types of odontogenic cysts and tumors.MethodsFifty-five cases of odontogenic cysts and tumors, including 15 ameloblastomas (AM), 5 adenomatoid odontogenic tumors (AOT), 5 ameloblastic fibromas (AF), 5 calcifying odontogenic cysts (COC), 10 dentigerous cysts (DC) and 15 odontogenic keratocysts (OKC) were investigated for the expression of SOX2 and OCT4 immunohistochemically.ResultsMost OKCs (86.7 %) and all AFs expressed SOX2 in more than 50 % of epithelial cells. Its immunoreactivity was moderate-to-strong in all epithelial cell types in both lesions. In contrast, SOX2 expression was undetectable in AOTs and limited to the ameloblast-like cells in a minority of AM and COC cases. Most DCs showed positive staining in less than 25 % of cystic epithelium. Significantly greater SOX2 expression was noted in OKC compared with DC or AM, and in AF compared with COC or AOT. OCT4 rarely expressed in odontogenic lesions with the immunoreactivity being mild and present exclusively in OKCs.ConclusionsSOX2 is differentially expressed in odontogenic cysts and tumors. This could be related to their diverse cells of origin or stages of histogenesis. The overexpression of SOX2 and OCT4 in OKC indicates the acquired stem-like property. Future studies should investigate whether the overexpression of OCT4 and SOX2 contributes to the aggressive behaviors of the tumors.

UNUSUAL PATHWAY OF DIAGNOSIS OF A RARE CASE: PERIPHERAL AMELOBLASTOMA

<h3>Background</h3> This case report highlights the varying differential diagnoses that finally led to the diagnosis of the peripheral ameloblastoma. It goes through the unexpected journey in reaching the diagnosis of this particular patient owing to varying presentations and unexpected findings. <h3>Discussion</h3> A 75-year-old woman was referred to the Royal Lancaster Infirmary maxillofacial surgery under the 2-week wait pathway for a right buccal swelling. The patient was referred by her general dental practitioner for a lump adjacent to the upper right maxillary tuberosity. The patient had bleeding from the lesion intermittently, raising suspicion of a possible malignancy. An incisional biopsy was performed and the initial impression for histology was cylindroma or eccrine spiral adenoma; however, the histopathologist confirmed the specimen was from the oral mucosa and a working diagnosis of low-grade salivary type neoplasm was reached. An excisional right buccal sulcus biopsy of the lesion was performed and showed infiltration of a basaloid tumor arising from squamous epithelium. The tumor islands were composed of basaloid tumor cells with peripheral palisading. There was no increase in mitotic activity. The overall appearance was consistent with an extraosseous ameloblastoma. Because of the differences between histology results, the sample was sent for further analysis and confirmation to Newcastle University, where it was confirmed to be a peripheral ameloblastoma. <h3>Conclusions</h3> The case highlights the difficult histologic appearance of a peripheral ameloblastoma and shows the need for thorough history and investigations to ensure the correct diagnosis and treatment.

MicroRNA-1-3p Suppresses Malignant Phenotypes of Ameloblastoma Through Down-Regulating Lysosomal Associated Membrane Protein 2-Mediated Autophagy.

Objective: Several clinical trials have suggested that autophagy inhibition is a promising approach for cancer therapy. However, the implications of autophagy in ameloblastoma (AB) remain undiscovered. This study investigated the dysregulated autophagy and its regulatory mechanisms in AB.Methods: The expression and distribution of autophagy-related proteins including B-cell lymphoma-2-interacting protein-1 (Beclin1), microtubule-associated protein 1 light chain 3 (LC3) II/I and lysosomal associated membrane protein 2 (LAMP2) were detected in AB and normal oral mucosa (NOM) tissues by immunohistochemistry and western blot analyses. Under transmission electron microscopy, the autophagy of AB was observed. LAMP2 was a potential target mRNA of miR-1-3p. Quantitative Real-time PCR (qRT-PCR) analysis was utilized for examining LAMP2 and miR-1-3p in AB tissues as well as AM-1 cells. The correlation between LAMP2 and miR-1-3p was analyzed in AB. After transfection with miR-1-3p mimic or inhibitor, LAMP2 expression, proliferation, migration, and invasion were separately detected in AM-1 cells. Rescue assays were finally presented.Results: Our results showed that Beclin1 was lowly expressed as well as LC3II/I and LAMP2 were highly expressed in AB. Autophagosomes were observed in AB. MiR-1-3p was lowly expressed in AB, which exhibited negative correlations to LAMP2 expression. MiR-1-3p up-regulation significantly lowered LAMP2 expression in AM-1 cells. Furthermore, miR-1-3p overexpression restrained proliferative, migrated, and invasive capacities of AM-1 cells, which were ameliorated by LAMP2 overexpression.Conclusion: Our findings demonstrated that miR-1-3p suppressed malignant phenotypes of AB through down-regulating LAMP2-mediated autophagy, which could become an underlying target for AB therapy.

Computer tomographic differential diagnosis of ameloblastoma and odontogenic keratocyst: classification using a convolutional neural network.

To analyse the automatic classification performance of a convolutional neural network (CNN), Google Inception v3, using tomographic images of odontogenic keratocysts (OKCs) and ameloblastomas (AMs). For construction of the database, we selected axial multidetector CT images from patients with confirmed AM (n = 22) and OKC (n = 18) based on a conclusive histopathological report. The images (n = 350) were segmented manually and data augmentation algorithms were applied, totalling 2500 images. The k-fold × five cross-validation method (k = 2) was used to estimate the accuracy of the CNN model. The accuracy and standard deviation (%) of cross-validation for the five iterations performed were 90.16 ± 0.95, 91.37 ± 0.57, 91.62 ± 0.19, 92.48 ± 0.16 and 91.21 ± 0.87, respectively. A higher error rate was observed for the classification of AM images. This study demonstrated a high classification accuracy of Google Inception v3 for tomographic images of OKCs and AMs. However, AMs images presented the higher error rate.

Gamma Knife for Recurrent Ameloblastoma with Cavernous Sinus Metastasis: A Case Report

Ameloblastoma (AME) is a rare, benign intraosseous progressively growing odontogenic tumor. Due to its invasive behavior, the rate of recurrence is high. Recurrent AME tends to transform malignantly and metastatic. Lung is the most common sites of AME metastasis, followed by lymph nodes. Here we present a case of AME with intracranial metastasis. A 26-year-old woman who had recurrent AME in the left jaw. After the second resection, AME metastasis to the cavernous sinus, sellar and suprasellar regions. Because the metastatic tumor was unresectable, she received Gamma Knife instead. After 3 years follow-up, the tumor was well controlled. In conclusion, Gamma Knife can be a feasible option for unresectable Oligometastatic AME.

Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma.

Increased lipogenesis and lipid droplet accumulation are observed in diverse tumors, and these processes are associated with poor prognosis in several tumors, representing potential therapeutic targets. The presence of lipid droplets in odontogenic tissues and/or tumors is unknown. Immunohistochemistry for perilipin 1 and adipophilin was performed in 12 human tooth germs (TG), 27 conventional ameloblastoma (AM), and 8 ameloblastic carcinoma (AC) samples. Cytoplasmic staining was analyzed using an immunoreactive score (IRS), and the results were compared for the TG, AM, and AC samples by Kruskal-Wallis test followed by Dunn's post-test and confirmed by Mann-Whitney U test. Perilipin 1 was negative in 91.7% of the TG samples, positive in 48.2% of the AM samples, and positive in 87.5% of the AC samples. Adipophilin was positive in 100% of the TG samples, 92.6% of the AM samples, and 100% of the AC samples. The perilipin 1 and adipophilin IRS revealed statistically significant differences between the TG, AM, and AC samples (p=.007 and p=.018, respectively). The perilipin 1 levels among the TG and AC samples were statically significant (**p=.0085), as well as the adipophilin levels when TG and AM samples were compared (**p<.0029). Adipophilin exhibits significant activity in human tooth development. The immunoexpression of perilipin 1 and adipophilin in the AM and AC samples suggests the presence of lipid droplets, providing further evidence of metabolic alterations in these tumors. Additional studies with larger samples and alternative techniques are necessary to confirm these findings.

A Long-Standing Giant Mandibular Ameloblastoma and its Management with Microvascular Free Fibular Graft: a Case Report.

Ameloblastoma is one of the most common benign epithelial odontogenic tumors of jaws. We report a case of long-standing slow-growing giant ameloblastoma involving almost all of mandibular bone. The solid multicystic lesion was excised, and the histopathological examination showed the follicular type of ameloblastoma. Furthermore, the defect was reconstructed with microvascular osteocutaneous free fibular graft.

Identification of circ_0089153/miR-608/EGFR p53 axis in ameloblastoma via MAPK signaling pathway.

This study investigated the role of circular RNAs (circRNAs) in the pathogenesis of ameloblastoma (AB), identifying potential novel targets for future targeted therapy. CircRNA and microRNA (miRNA) profiling in AB were built with microarrays. Six novel circRNAs were validated, circ-miRNA networks were delineated. Hsa-miR-608 was filtered over cross-comparison between database screening, miRNA microarray and validated. Circ-miRNA binding sponge was validated via luciferase reporter assay. Downstream mRNAs were screened. Regulation between miRNAs and mRNAs was confirmed in vitro. Gene interaction networks and circRNA-miRNA-mRNA interaction pathway enrichment analyses were established. Six differentially expressed circRNAs were selected and validated. According to miRNAs and pathways predicted, six correlated miRNAs were selected, hsa-miR-608 was filtered and validated. The hsa_circ_0089153/hsa-miR-608 binding sponge was validated. Downstream gene interaction networks showed that EGFR and p53 had the strongest co-expression. In vitro transfection results confirmed the suppressive function of miR-608 and EGFR p53. Hsa_circ_0089153/hsa-miR-608/EGFR p53 interaction pathway enrichment analysis confirmed functions mainly enriched in MAPK and related signaling pathways regulating AB progression. Six novel circRNAs were identified. Hsa_circ_0089153/hsa-miR-608 sponging was validated, hsa-miR-608 downregulated EGFR and p53, which might further regulate cell proliferation, differentiation, apoptosis, and cell cycle processes via the MAPK signaling pathway.

Differentiated Immunohistochemical Expression of Osteoclastogenic Markers in Radicular Cyst, Odontogenic Keratocyst, and Ameloblastoma

The aim of this study was to investigate the osteoclastogenesis process by means of immunohistochemical markers for receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), interleukin-6 (IL-6), and cathepsin K (CTSK) antigens in osteolytic lesions of maxillary bones. The sample consisted of 23 radicular cysts (RC), 25 odontogenic keratocysts (OKC), and 25 ameloblastomas (AM). RANKL was statistically higher in RC (49.6±15.2/53.7±18) and OKC (48.6±15.1/51.4±16.8) when compared with AM (37.2±12.5/36.4±13) in the epithelium and connective tissue. OPG was lower in OKC (34.8±18.5) only in connective tissue when compared with RC (44.5±11.2). The expression of RANKL was statistically higher than OPG in RC (epithelium and connective tissue) and OKC (connective tissue). For IL-6, a statistical difference was observed only in the connective tissue between groups, with higher expression in RC (48.2±15) and lower in OKC (22±11.9). The expression of IL-6 was correlated with the intensity of the inflammatory infiltrate. CTSK was statistically higher in AM (34±19) and OKC (29±13.8) compared with RC (19±10.5). According to the results of the present research the bone resorption in cysts and odontogenic tumors occurs through different mechanisms. The ostoclastogenic process in lesions with aggressive clinical behavior, as AM and OKC, seems to be associated with the expression of CTSK. In contrast, lesions with inflammatory etiology, as RC, the expression of IL-6 seems to have an important role in the bone resorption process. The highest expression of RANKL under the expression of OPG also seems to contribute to the growth mechanism of RC and OKC.

Conceptual changes in ameloblastoma: Suggested re-classification of a "veteran" tumor.

The merging of ameloblastoma (AM) with mural unicystic ameloblastoma (UAM-M) was suggested by the 2017 WHO based on similar treatment needs. In an international multicenter study, we investigated the characteristics of their merged product (merged-AM) and raised the possibility of unifying AM and UAM (total-AM). AM and UAM (luminal/intraluminal/mural), separate and combined, were analyzed for demographic/clinical/radiological features. ANOVA and chi-square tests were followed by univariate and multivariate analyses, and significance was set at p<.05. The patients' mean age was 39.6±20.3years in merged-AM (147 AM, 76 UAM-M), 45.1±19.4years in AM (p=.009). Merged-AM comprised 51.3% multilocular/48.7% unilocular tumors, AM comprised 72.5%/27.5%, respectively (p<.001). Merged-AM was associated with impacted teeth in 30.8%, AM in 18% (p=.023). The probability of merged-AM for multilocularity increased by 2.4% per year of age (95%CI 0.6-4.2, p=.009). Association with impacted teeth decreased by 7.9% per year of age (95%CI 1.9-14.39, p=.009). Merged-AM did not differ from total-AM (p>.05). Merged-AM partially differed from AM, but differences appeared to diminish in an age/time-wise manner. Merged-AM and total-AM were nearly indistinguishable. Therefore, AM and UAM may be considered a continuous spectrum of one type of tumor, further necessitating revision of the treatment approaches.

Maxillary ameloblastoma with lung metastasis: Case report of a rare tumor

Ameloblastomas are low-grade neoplasms of odontogenic epithelium that account for about 1% of all oral tumors and about 10% of odontogenic tumors. Rarely, these tumors have a potential of distance metastasis, and once they do metastasize, they are termed as metastatic ameloblastoma. This article aims at describing a case of a rare form of maxillary ameloblastoma that metastasized to the lung and challenges in its management in settings with limited resources. A 24-year-old African male presented with a massive swelling on the right side of the face for 2 years in 2018. He was previously operated on for a swelling on the right side of the maxilla in 2012, which was histologically diagnosed as ameloblastoma. Clinical and radiological evaluation revealed a massive maxillary tumor that had a local extension to the brain. X-ray and computed tomography (CT) scan of chest pointed out to metastatic mass in the lungs. Histology of the recurrent tumor mass revealed it to be follicular ameloblastoma, and CT-guided fine-needle aspiration cytology of the lung mass showed microscopic features of ameloblastoma similar to the primary jaw tumor.

Human cytomegalovirus is present in the odontogenic epithelium of ameloblastoma

ABSTRACT Background: The factor behind the activation of the remnant odontogenic tissues and development of odontogenic cysts and tumors is poorly understood.This study aimed to investigate the presence of human cytomegalovirus (HCMV) in dentigerous cyst (DC), odontogenic keratocyst (OKC), and ameloblastoma (AB). Methods: The study included 41 samples, which distributed into DC (n=13), OKC (n=12), and AB (n=16). Conventional PCR assay and IHC analysis were used to detect the HCMV-DNA and HCMV glycoprotein B (HCMV-gB) respectively. Results: HCMV-DNA was detected in 10 samples (62.5%) of AB, four samples (30.8%) of DC, and three samples (25 %) of OKC respectively (χ2 test = 1.195, p= 0.247). Meanwhile, HCMV-gB was found in 12 (75%) of AB, in 2 (15.4%) of DC, and absent in OKC (0.0%) (χ2 test = 4.122, p= 0.042). Conclusions: The high prevalence of HCMV inside the odontogenic epithelium of AB could indicate a possible role of the virus in the oncogenesis and/or oncomodulation of the AB. Additionally, we recommend the IHC for the detection of HCMV in the odontogenic tumors like AB.

Extraosseous Ameloblastoma of the buccal mucosa: A case report of a rare entity

Extraosseous ameloblastoma is the peripheral counterpart of the usual well known central ameloblastoma. The most commonly involved sites include the lingual gingiva of the mandible, lips, and palate, with only a few reports of peripheral ameloblastoma in the buccal mucosa cited in the literature. This article aims to describe a case of peripheral ameloblastoma of buccal mucosa, its presentation, the dilemma in diagnosis, and management. We emphasize the need to include this rare entity in the differential diagnosis of buccal mucosal swellings.

Genetic factors in the pathogenesis of ameloblastoma, dentigerous cyst and odontogenic keratocyst.

Ameloblastoma (AB), dentigerous cyst (DC) and Odontogenic keratocyst (OKC) are odontogenic lesions with propensity to malignant transformation or local invasion. The molecular mechanisms of development of these lesions are not fully understood. However, some researches have reported dysregulation of tumor suppressor genes or oncogenes in these lesions. Down-regulation of P53 gene has been reported in AB, DC and OKC. Moreover, several long non-coding RNAs such as ENST00000512916 and KIAA0125 have been dysregulated in AB tissues. Single nucleotide polymorphisms within a variety of genes have been associated with certain types of odontogenic lesions. In the current review, we summarize the current data about the expression pattern of genes in these lesions and the observed association between genetic polymorphisms and development of these lesions.

A Case Report with Literature Review: Recurrence of Peripheral Ameloblastoma with Intracranial Extension

A Case Report with Literature Review: Recurrence of Peripheral Ameloblastoma with Intracranial Extension