[Three-dimensional radiographic features of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor].

OBJECTIVE: To analyze the three-dimensional radiographic characteristics of calcifying odontogenic cyst and calcifying epithelial odontogenic tumor using spiral computed tomography (CT) and cone-beam computed tomography (CBCT). METHODS: Clinical records, histopathological reports, and CBCT or non-enhanced spiral CT images of 19 consecutive patients with calcifying odontogenic cyst (COC) and 16 consecutive patients with calcifying epithelial odontogenic tumor (CEOT) were retrospectively acquired, and radiographic features, including location, size, expansion, internal structure and calcification, were analyzed. RESULTS: Among the 19 COC cases (12 males and 7 females, with an average age of 27 years), 89.5% (17/19) of the lesions originated from the anterior and premolar areas, 100.0% of them exhibited cortex expansion, and 78.9% had discontinued cortex. Among the 16 CEOT cases (3 males and 13 females, with an average age of 36 years), 81.3% (13/16) of the lesions were in the premolar and molar areas, 56.3% of them exhibited cortex expansion, and 96.8% had discontinued cortex. According to the distribution of internal calcifications, these lesions were divided into: Ⅰ (non-calcification type): absence of calcification; Ⅱ (eccentric marginal type): multiple calcifications scattered along one side of the lesion; Ⅲ (diffused type): numerous calcifications diffusely distributed into the lesion; Ⅳ (plaque type): with a ≥ 5 mm calcified patch; Ⅴ (peri-coronal type): multiple calcifications clustered around impacted teeth. Calcifications were present in 73.7% of COC lesions, including 9 type Ⅱ, 3 type Ⅲ and 2 type Ⅳ lesions, and 42.8% of CEOT lesions had calcification images, including 2 type Ⅲ and 5 type Ⅴ lesions. Six COC lesions had odontoma-like images. Moreover, 8 of 9 type Ⅰ CEOTs were histologically Langerhans cell-rich subtype, which had a smaller size (with an average mesiodistal diameter of 17.8 mm) and were not associated with impacted teeth. CONCLUSION: COC lesions tended to originate from the anterior part of the jaw and exhibit cortex expansion, and were sometimes associated with odontoma. CEOT commonly occurred in the posterior jaw and had discontinued cortex. Two lesions had significantly different calcification map. Over 70% of COC lesions had calcification images, which were mostly scattered along one side of the cysts, far from the impacted teeth. Approximately 60% of CEOT lesions exhibited smaller size and non-calcification, and the remaining CEOT cases often had calcification images clustered around the impacted teeth.

Higher immunoexpression of CK14 from the Wnt-1/ß-catenin pathway in the development of odontomas.

Tooth development depends on a series of reciprocal signaling interactions between the oral epithelium and ectomesenchyme. This study aimed to investigate the role of CK14, a protein involved in Wnt-1/ß-catenin signaling, in odontogenesis and the development of odontomas. This cross-sectional, retrospective, immunohistochemical study analyzed 30 compound odontomas, 30 complex odontomas, and 17 tooth germs. Higher immunoexpression of CK14 was observed in odontogenic epithelial cells of tooth germs (p < 0.001) and odontogenic epithelial cells of odontomas (p < 0.001). There was higher immunoexpression of Wnt-1 and ß-catenin proteins in epithelial cells of tooth germs (p = 0.002 and p < 0.001, respectively), as well as in the ectomesenchyme of odontomas (p = 0.003 and p < 0.001, respectively). ß-Catenin was moderately and significantly correlated with CK14 in the membrane of reduced enamel epithelial cells in odontomas (p = 0.007). Higher immunoexpression of CK14 was observed in the odontogenic epithelium during the bud and cap stages and lower immunoexpression in the internal enamel epithelium during the bell stage. In odontomas, lower expression of Wnt-1/ß-catenin and higher immunoexpression of CK14 were found in odontogenic epithelial cells, especially adjacent to the mineralized material resembling the tooth formed in these lesions.

Pediatric Odontogenic Tumors.

Odontogenic tumors are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. Some odontogenic tumors demonstrate strong predilection for pediatric patients including the unicystic ameloblastoma, adenomatoid odontogenic tumor, ameloblastic fibroma, ameloblastic fibro-odontoma, odontoma, and primordial odontogenic tumor. In this review, we discuss the clinical, radiographic, histopathologic, and molecular characteristics of select odontogenic tumors that demonstrate pediatric predilection and review management.

Revisiting the History of Odontoma, with Special Reference to Its Original Illustration.

BACKGROUND: Practically every facet of the most common odontogenic tumor, odontoma, has been covered by an extensive volume of literature. However, uncertainty about its precise history has persisted. MATERIALS AND METHODS: The historical evolution of odontoma was traced with reference to the original illustrations that accompanied European and American reports published at the beginning of the 19th century and also at the turn of the century. RESULTS: The prevailing views regarding the first description of odontoma by Oudet of Paris in 1809 and the original designation "odontome" by Broca of Paris in 1867 are not entirely accurate. Before Broca's suggested term, "exostose dentaire" (dental exostosis) and "tumeur dentaire" (dental tumor) proposed by Oudet and Forget of Paris, respectively, were popular terms adopted in France, while in Briatin the terms "warty tooth" and "supernumerary teeth" proposed by Salter and Tomes of London, respectively, were widely coined. The original illustrations of complex odontoma were published by Wedl of Vienna in 1851, and in 1862 Tomes published the first drawing of compound odontoma denticles. Before the advent of diagnostic radiography in the early 1900s, spontaneous exposure or eruption of odontoma followed by secondary infection was very common. In 1887-1888, Bland Sutton of London criticized Broca's monumental research and formulated the first modern classification which, in essence, remains valid today. At that time, large osteomas of the maxilla were inappropriately classified as odontomas by many pathologists because of Bland Sutton's influential view. Interestingly, the first radiographic evidence of odontoma was published by the American oral surgeon Gilmer in 1899. CONCLUSION: In view of their fundamental achievements, the names of Wedl, Salter, Broca and Bland Sutton have been closely associated with the true history of odontoma.

The molecular basis of odontogenic cysts and tumours.

The advances in molecular technologies have allowed a better understanding of the molecular basis of odontogenic cysts and tumours. PTCH1 mutations have been reported in a high proportion of odontogenic keratocyst. BRAF p.V600E are recurrent in ameloblastoma and KRAS p.G12V/R in adenomatoid odontogenic tumour, dysregulating the MAPK/ERK pathway. Notably, BRAF p.V600E is also detected in ameloblastic carcinoma, but at a lower frequency than in its benign counterpart ameloblastoma. Recently, adenoid ameloblastoma has been shown to be BRAF wild-type and to harbour CTNNB1 (ß-catenin gene) mutations, further suggesting that it is not an ameloblastoma subtype. CTNNB1 mutations also occur in other ghost-cell-containing tumours, including calcifying odontogenic cysts, dentinogenic ghost cell tumours and odontogenic carcinoma with dentinoid, but the link between CTNNB1 mutations and ghost cell formation in these lesions remains unclear. Regarding mixed tumours, BRAF p.V600E has been reported in a subset of ameloblastic fibromas, ameloblastic-fibrodentinomas and fibro-odontomas, in addition to ameloblastic fibrosarcoma. Such mutation-positivity in a subset of samples can be helpful in differentiating some of these lesions from odontoma, which is BRAF-wild-type. Recently, FOS rearrangements have been reported in cementoblastoma, supporting its relationship with osteoblastoma. Collectively, the identification of recurrent mutations in these aforementioned lesions has helped to clarify their molecular basis and to better understand the interrelationships between some tumours, but none of these genetic abnormalities is diagnostic. Since the functional effect of pathogenic mutations is context and tissue-dependent, a clear role for the reported mutations in odontogenic cysts and tumours in their pathogenesis remains to be elucidated.

Spatial distribution of CD34 protein in primordial odontogenic tumour, ameloblastic fibroma and the tooth germ.

BACKGROUND: Primordial odontogenic tumour is a benign mixed neoplasm of recent description, which has histological similarities with other odontogenic tumours such as the ameloblastic fibroma. In this article, we investigate the architecture of the sub-epithelial layer of mesenchymal cells expressing the marker CD34 in primordial odontogenic tumour. OBJECTIVE: Analyse the spatial patterns of CD34 expression in primordial odontogenic tumour and compare them with those in ameloblastic fibroma and the normal tooth germ by means of objective imaging approaches, to better characterise these lesions. METHODS: Two cases of primordial odontogenic tumour, four cases of ameloblastic fibroma and two cases of tooth germ in cap and bell stages were used for morphological, structural and immunohistochemical analyses. RESULTS: CD34 expression was found in vascular endothelium of primordial odontogenic tumour, ameloblastic fibroma and tooth germ. In addition, a characteristic sub-epithelial expression was observed only in primordial odontogenic tumour, corresponding to 84%-86% of the sample boundaries. Moreover, the zone expressing CD34 corresponded with a higher cellularity, which was absent in ameloblastic fibroma and tooth germ. CONCLUSION: Image analysis of the primordial odontogenic tumour architecture revealed characteristics absent in other odontogenic tumours and tooth germs. This study provides additional information to support the idea that this neoplasm is a distinct entity from early stage AF or developing odontoma.

MR appearance of a rare ameloblastic fibroma with formation of dental hard tissues with histopathologic correlation: a case report.

An ameloblastic fibroma with formation of dental hard tissues, which the classical name is ameloblastic fibro-odontoma (AFO), is a rare type of mixed odontogenic tumor. An 8-year-old boy was diagnosed with AFO, with an inhomogeneous high signal within the lesion shown by T2-weighted magnetic resonance imaging (MRI). Computed tomography (CT) imaging revealed a unilocular low CT value area of 24 × 19 × 26 mm with buccolingual bony expansion and cortical bone thinning on the left side of the mandible including the crown of the mandibular left second molar. In addition, multiple calcified bodies were detected within the lesion, one of which had a CT value of approximately 2200 HU, equivalent to that of enamel. MRI indicated the lesion to be sized 24 × 19 × 25 mm along with buccolingual bony expansion in the left side of the mandible. Additionally, the lesion showed an internal inhomogeneous high signal, while a portion had an especially high signal in T2-weighted images. That particularly high signal area coincided with the nodular growth area of mucus-rich mesenchymal components without the epithelial component in histopathology findings. The particularly high signal revealed by T2-weighted imaging could be attributed to the mucus-rich component. MRI was found useful for revealing differences in the internal histopathological properties of an AFO in our patient.

O papel de proteínas das vias WNT/ß-Catenina, TGF-ß/BMP4 e SHH na odontogênese e odontomas / The role of proteins from the WNT/ß-Catenin, TGF-ß/BMP4 and SHH pathways in odontogenesis and odontomas

O desenvolvimento do dente depende de uma série de interações sinalizadoras recíprocas entre o epitélio oral (EO) e o ectomesênquima derivado da crista neural, a via WNT com o TGF-ß e BMP4 tem sido implicada na tumorigênese. A via de sinalização tipo Wingless (Wnt) / ß-catenina é essencial para a ativação precoce da odontogênese e no desenvolvimento de tumores odontogênicos. O TGF-ß e as BMPs tem sido associadas aos processos de dentinogênese reacionária e reparadora. A sinalização de Shh pode regular a proliferação celular no ectomesênquima dentário, controlando assim a morfogênese dentária. O objetivo da pesquisa foi investigar a atuação de algumas proteínas das vias na odontogênese e na formação de odontomas e tumores odontogênicos mistos benignos, para isto, foi desenvolvido um estudo seccional restrospectivo e imuno-histoquímico contendo 23 odontomas compostos, 21 odontomas complexos, 17 germes dentários, 05 fibro-odontomas ameloblásticos e 01 fibroma ameloblástico. Os resultados encontrados demonstraram maiores imunoexpressões da via WNT/ß-catenina no epitélio dos germes dentários (p<0,001) e no fibroma ameloblástico, enquanto que, esteve no ectomesênquima dos odontomas (p<0,001) e fibro-odontomas ameloblásticos. A via WNT/ßcatenina correlacionou-se moderadamente e significativamente com a CK14 no epitélio (p = 0,007) dos odontomas. A BMP4 foi imunoexpressa, especialmente, no ectomesênquima dos odontomas complexos (mediana = 33,7; p<0,001). A via Shh foi mais imunoexpressa no epitélio dos germes dentários (p<0,001) e no ectomesênquima dos odontomas complexos (p=0,029). De forma similar, o TGFß apresentou maior imunoexpressão no epitélio dos germes dentários (p<0,001) e no ectomesênquima dos odontomas complexos (p = 0,002). O dente em desenvolvimento exibiu maiores concentrações para estas proteínas no epitélio odontogênico nas fases de botão e capuz e a expressão diferencial ocorreu, principalmente, no ectomesênquima dos tumores, o que indica que esse componente é de fato mais proliferativo (AU).

Tooth development depends on a series of reciprocal signaling interactions between oral epithelium (EO) and neural crest-derived ectomesenchyme, the WNT pathway with TGF-ß and BMP4 has been implicated in tumorigenesis. The Wingless (Wnt)/ß-catenin signaling pathway is essential for the early activation of odontogenesis and the development of odontogenic tumors. TGF-ß and BMPs have been associated with reactionary and reparative dentinogenesis processes. Shh signaling can regulate cell proliferation in dental ectomesenchyme, thus controlling dental morphogenesis. The objective of the research was to investigate the role of some proteins in the pathways in odontogenesis and in the formation of odontomas and benign mixed odontogenic tumors. tooth germs, 05 ameloblastic fibro-odontomas and 01 ameloblastic fibroma. The results found showed higher immunoexpressions of the WNT/ß-catenin pathway in the epithelium of tooth germs (p<0.001) and in ameloblastic fibroma, while it was in the ectomesenchyme of odontomas (p<0.001) and ameloblastic fibroodontomas. The WNT/ß-catenin pathway correlated moderately and significantly with CK14 in the epithelium (p = 0.007) of odontomas. BMP4 was immunoexpressed, especially in the ectomesenchyme of complex odontomas (median = 33.7; p<0.001). The Shh pathway was more immunoexpressed in the epithelium of tooth germs (p<0.001) and in the ectomesenchyme of complex odontomas (p=0.029). Similarly, TGF-ß showed higher immunoexpression in the epithelium of tooth germs (p<0.001) and in the ectomesenchyme of complex odontomas (p = 0.002). The developing tooth exhibited higher concentrations of these proteins in the odontogenic epithelium in the bud and cap phases and the differential expression occurred mainly in the ectomesenchyme of the tumors, which indicates that this component is in fact more proliferative (AU).

Ameloblastic Fibro-Odontoma: At the Crossroad Between "Developing Odontoma" and True Odontogenic Tumour.

Ameloblastic fibro-odontoma (AFO) is a controversial, rare benign mixed odontogenic tumour that was re-defined as "developing odontoma" in the 2017 WHO classification arguing that once dental hard tissues form, it is programmed to transform into odontoma. However, AFO still remains unclear in terms of its nature. We aimed to analyze a large series of AFOs and compare it to a large series of odontomas (ODs) in an attempt to set cut-off diagnostic parameters between these entities and discuss latest updates on AFO histopathologic, clinical and molecular features. A total of 23 well-documented AFOs were analyzed versus 310 ODs focusing on the age of the patients and size of the lesions. For AFO, mean age was 9.4 ± 3.9 years (range 3-16 years) and mean size (greatest diameter) was 2.9 ± 1.5 cm (range 0.8-5.5 cm). For OD-mean age was 26.5 ± 15.6 years (range 3-81 years), mean size 1.9 ± 0.9 cm (range 1-5 cm). Receiver operating curve (ROC) showed that a cut-off age of 13.5 years and below [area under the curve (AUC) 0.902, 95%CI 0.859-0.945; p < 001; sensitivity 80%, specificity 87%] and a cut-off size of 2.1 cm and above are likely to be associated with AFO (AUC 0.7, 95%CI 0.574-0.827; p = 0.001; sensitivity 57%, specificity 77%). Thus, the combination of age and lesion size may be used to distinguish between lesions of a true neoplastic nature (i.e., AFO) and hamartomatous formation (i.e., OD). Further molecular and genetic specifications are needed to provide a better understanding on the pathogenesis of AFO in support of our suggestion and aid in an accurate classification of AFO.

Diagnosis of ameloblastic fibro-odontoma: case report / Diagnóstico de fibro-odontoma ameloblástico: relato de caso

Objective: the present report describes the clinical, radiographic, and histopathological features of an ameloblastic fibro-odontoma (AFO) lesion. Case report: we report a clinical case of a 14-year-old boy with asymptomatic edema. Panoramic radiography detected a unilocular lesion with defined margins located in the posterior region of the mandible. The internal structure of the lesion presented several degrees of radiopacity with the involvement of the third molar. Cone-beam computed tomography revealed expanded buccal and lingual cortical bones, perforation of the lingual cortical bone, and displacement of the mandibular canal. AFO was suspected based on the radiographic and clinical characteristics. Total excision was performed and histologically examined, confirming the diagnosis of AFO. No recurrence occurred during a 24-month follow-up period. Final considerations: the evaluation of the clinical, radiographic, and histopathologic findings needs to be accurate for a correct diagnosis and appropriate treatment for case of AFO since the presentation is often asymptomatic.(AU)

Objetivo: o presente relato descreve as características clínicas, radiográficas e histopatológicas de uma lesão de fibro-odontoma ameloblástico (FOA). Relato de caso: relatamos o caso clínico de um menino de 14 anos com edema assintomático. A radiografia panorâmica detectou lesão unilocular com margens definidas e localizada na região posterior da mandíbula. A estrutura interna da lesão apresentava vários graus de radiopacidade com envolvimento do terceiro molar. A tomografia computadorizada de feixe cônico revelou as corticais ósseas vestibular e lingual expandidas, perfuração da cortical óssea lingual e deslocamento do canal mandibular. FOA foi a hipótese diagnóstica com base nas características radiográficas e clínicas. A excisão total foi realizada e examinada histologicamente, confirmando o diagnóstico de FOA. Nenhuma recorrência ocorreu durante um período de acompanhamento de 24 meses. Considerações finais: a avaliação das características clínicas, radiográficas e histopatológicas contribuíram para um diagnóstico correto e o tratamento adequado para o caso de FOA, uma vez que a lesão é frequentemente assintomática.(AU)

Analysis of Protein Immunoexpression and Its Interrelationship in the Pathogenesis of Odontomas and Ameloblastic Fibro-Odontomas: A Systematic Review.

Odontomas and ameloblastic fibro-odontomas (AFOs) are the result of a developmental anomaly of odontogenic tissues. A literature review of proteins immunoexpressed in odontomas and AFOs was conducted in order to determine which proteins are involved in the pathogenesis of these lesions. AFO was changed to early odontoma in the 2017 WHO classification and will also be discussed in this article. A literature search was performed in the following electronic databases: PubMed/MEDLINE, Web of Science, Scopus, EMBASE, Lilacs, Cochrane Collaboration Library, and Science Direct. The research question was developed according to the population, intervention, comparison, and outcome (PICO) framework: Which proteins are related to the differentiation of odontomas and what is their interrelationship with AFOs? Thirty articles met all inclusion criteria and were selected for this systematic review, totaling 355 cases of odontomas and 43 cases of AFO. Similar immunoexpression was observed in odontomas and AFOs. Immunoexpression of proteins involved in cell differentiation was higher in compound odontomas than in complex odontomas. Proteins involved in histodifferentiation and enamel formation were more frequent in odontomas. The immunoexpression of enamel matrix proteins differs between odontomas and tooth germs, with their persistence being related to the development of odontomas. Compound odontomas exhibit the highest immunoexpression of proteins involved in cellular histodifferentiation and the Wnt/beta-catenin pathway is involved in tumor formation.

Ameloblastic Fibroodontoma of Mandible Causing Tumor Induced Osteomalacia: A Case Report with Review of 88 Phosphaturic Oral Neoplasms.

Tumor induced osteomalacia (TIO) is a rare paraneoplastic syndrome associated with tumors secreting fibroblast growth factor 23, which induces osteomalacia. Microscopically, these tumors most commonly show benign phosphaturic mesenchymal tumors. We report the first case of phosphaturic ameloblastic fibro-odontoma (AFO) manifesting as osteomalacia. Our index patient was a 33-year-old male who was diagnosed with TIO and AFO in the mandible was identified as the cause. Our case is unique as AFO is considered as a hamartoma. To the best of our knowledge, there is no hamartoma reported till date causing phosphaturic osteomalacia. As AFO demonstrates mixed epithelial and mesenchymal origin, we propose a new histopathological subtype of TIO-"phosphaturic tumor of mixed epithelial and mesenchymal origin". A review of literature focused on TIO caused by oral lesions revealed 88 oral neoplasms which matched our search criteria. Due to the rarity and unpredictable behavior of TIOs, a high index of suspicion, a broad diagnostic approach, detailed history and multidisciplinary investigations are crucial for establishing the definitive diagnosis and proper treatment recommendations.

Evaluation of dentofacial asymmetry caused by odontomas using panoramic radiographs.

AIMS: To evaluate the presence of dentofacial asymmetry in patients with odontoma by panoramic radiography. METHODS: Panoramic images with odontoma were selected among all panoramic radiographs (3058 patients). Maxillary odontoma was detected in 27 patients while mandibular odontoma was detected in 25 patients. In addition, 30 patients with similar age and gender characteristics were selected as the control group. Skeletal angular, skeletal linear and dental measurements were performed on panoramic radiographs. The odontoma region and the opposite side of the odontoma of the individuals were examined. The dentofacial asymmetry of the odontoma groups was compared with the control group. Paired t-test was used to determine dentofacial asymmetry on the right and left side of the patients with odontoma. The ANOVA test was used for testing the differences among groups. RESULTS: As a result of study, no significant difference was found between the region of the odontoma and the symmetrical region in the maxilla and mandibula (P > 0.05). In the control group, a statistically significant difference was found in the angle between the mandibular canal and the mental foramen, lower incisor size, PFH/CutCat(°), and Co-Mc-Me(°) measurements (P < 0.05). In the maxillary and mandibular odontoma groups, a statistically significant difference was found in the angle between the mandibular canal and the menton, CH (mm), RH (mm), and CrH (mm) in the comparison of the odontoma and the control group (P < 0.05). CONCLUSIONS: No difference was found between the right and left sides of the jaws related with the asymmetry of the maxilla and mandible.

IKKß overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice.

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/ß-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKß (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKß in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKß in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased ß-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKß in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.

Odontomas in Frogs.

Odontomas are variably differentiated, hamartoma-like proliferations of odontogenic epithelium, pulp ectomesenchyme (odontoblasts), and dental matrix. Frogs are polyphyodont and homodont. Their teeth also differ from mammals in that they are restricted to the upper jaw in adults and lack a periodontal ligament and cementum, attaching directly to the underlying bone. Odontomas were identified in an African clawed frog (Xenopus laevis), a false tomato frog (Dyscophus guineti), and a tomato frog of unknown species (Dyscophus sp.). All of the examined odontomas were composed of numerous tooth-like structures comprising an arc of dentinal matrix lined on the convex surface by ameloblasts and on the concave surface by odontoblasts. Masson's trichrome and immunohistochemistry with pan-cytokeratin supported these findings. The pathogenesis of these lesions may be displacement of the dental lamina, which has been shown in research studies to lead to de novo proliferation of dental elements in frogs.

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Wnt/ß-catenin signaling, which is activated in odontomas, reduces Sema3A expression to regulate odontogenic epithelial cell proliferation and tooth germ development.

Odontomas, developmental anomalies of tooth germ, frequently occur in familial adenomatous polyposis patients with activated Wnt/ß-catenin signaling. However, roles of Wnt/ß-catenin signaling in odontomas or odontogenic cells are unclear. Herein, we investigated ß-catenin expression in odontomas and functions of Wnt/ß-catenin signaling in tooth germ development. ß-catenin frequently accumulated in nucleus and/or cellular cytoplasm of odontogenic epithelial cells in human odontoma specimens, immunohistochemically. Wnt/ß-catenin signaling inhibited odontogenic epithelial cell proliferation in both cell line and tooth germ development, while inducing immature epithelial bud formation. We identified Semaphorin 3A (Sema3A) as a downstream molecule of Wnt/ß-catenin signaling and showed that Wnt/ß-catenin signaling-dependent reduction of Sema3A expression resulted in suppressed odontogenic epithelial cell proliferation. Sema3A expression is required in appropriate epithelial budding morphogenesis. These results suggest that Wnt/ß-catenin signaling negatively regulates odontogenic epithelial cell proliferation and tooth germ development through decreased-Sema3A expression, and aberrant activation of Wnt/ß-catenin signaling may associate with odontoma formation.

Mixed odontogenic tumors in four young dogs: ameloblastic fibroma and ameloblastic fibro-odontoma.

Ameloblastic fibroma (AF) and ameloblastic fibro-odontoma (AFO) are mixed odontogenic tumors (odontogenic tumors with induction) that are reported only rarely in dogs. These tumors are histologically complex and, to a degree, recapitulate the early stages of tooth development, comprising 2 types of tissue: neoplastic odontogenic epithelium, and induced ectomesenchyme (dental pulp). AFOs are distinguished from AFs by the additional presence of hard dental matrices such as dentin. Herein, we describe the key diagnostic features of AF and AFO in 4 young dogs.