The Molecular Pathology of Odontogenic Tumors: Expanding the Spectrum of MAPK Pathway Driven Tumors

Odontogenic tumors comprise a heterogeneous group of lesions that arise from the odontogenic apparatus and their remnants. Although the etiopathogenesis of most odontogenic tumors remains unclear, there have been some advances, recently, in the understanding of the genetic basis of specific odontogenic tumors. The mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) pathway is intimately involved in the regulation of important cellular functions, and it is commonly deregulated in several human neoplasms. Molecular analysis performed by different techniques, including direct sequencing, next-generation sequencing, and allele-specific qPCR, have uncovered mutations in genes related to the oncogenic MAPK/ERK signaling pathway in odontogenic tumors. Genetic mutations in this pathway genes have been reported in epithelial and mixed odontogenic tumors, in addition to odontogenic carcinomas and sarcomas. Notably, B-Raf proto-oncogene serine/threonine kinase (BRAF) and KRAS proto-oncogene GTPase (KRAS) pathogenic mutations have been reported in a high proportion of ameloblastomas and adenomatoid odontogenic tumors, respectively. In line with the reports about other neoplasms that harbor a malignant counterpart, the frequency of BRAF p.V600E mutation is higher in ameloblastoma (64% in conventional, 81% in unicystic, and 63% in peripheral) than in ameloblastic carcinoma (35%). The objective of this study was to review MAPK/ERK genetic mutations in benign and malignant odontogenic tumors. Additionally, such genetic alterations were discussed in the context of tumorigenesis, clinical behavior, classification, and future perspectives regarding therapeutic approaches.

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.

Mandibular odontoameloblastoma in a rat and a horse

Odontoameloblastoma (OA) is a mixed odontogenic tumor that is an ameloblastoma with concurrent histologic evidence of odontoma differentiation. As a mixed tumor, OA is a tripartite lesion comprised of neoplastic odontogenic epithelium, induced dental ectomesenchyme (dental pulp), and mineralized dental matrix. Although rare, OA represents a diagnostic conundrum, as it is histologically closely related to 2 other mixed odontogenic tumors: odontoma (complex and compound) and ameloblastic fibro-odontoma. Herein we describe an OA arising from the mandible of a 4-mo-old Fischer 344 rat that had been exposed in utero to the mutagen ENU (N-ethyl-N-nitrosourea), and a naturally occurring lesion in a 2-y-old Appaloosa horse. In order to satisfy the diagnostic criteria for this lesion, mineralized dental matrix in relationship to neoplastic odontogenic epithelium must be identifiable within the OA lesion. This group of odontogenic tumors is differentiated by the degree to which the dental matrix is organized and the relative proportions of pulp ectomesenchyme, odontogenic matrix, and odontogenic epithelium.

A Case of Ameloblastic Fibroodontoma Extending Maxillary Sinus with Erupted Tooth: Is Transcanine Approach with Alveolectomy Feasible?

Ameloblastic fibroodontoma (AFO) is a rare entity of mixed odontogenic tumors and frequently arises from posterior portion of the maxilla or mandible in first two decades of life. Herein, a 35-year-old woman with a noncontributory medical history who presented with a progressive left maxillary toothache, left maxillary first molar tooth mobility, and swelling in the left maxillary molar area for the last 2 months was reported. Radiologically, a tumor that originated from periapical area of the second mature molar teeth of maxilla was seen and additively unerupted tooth was not detected. The histopathologic examination revealed AFO. The patient is disease-free for five years after treated with limited segmental alveolectomy combining with Caldwell-Luc procedure.

Defects of the Carney complex gene (PRKAR1A) in odontogenic tumors

The surgical treatment of some odontogenic tumors often leads to tooth and maxillary bone loss as well as to facial deformity. Therefore, the identification of genes involved in the pathogenesis of odontogenic tumors may result in alternative molecular therapies. ThePRKAR1Agene displays a loss of protein expression as well as somatic mutations in odontogenic myxomas, an odontogenic ectomesenchymal neoplasm. We used a combination of quantitative RT-PCR (qRT-PCR), immunohistochemistry, loss of heterozygosity (LOH) analysis, and direct sequencing of allPRKAR1Aexons to assess if this gene is altered in mixed odontogenic tumors. Thirteen tumors were included in the study: six ameloblastic fibromas, four ameloblastic fibro-odontomas, one ameloblastic fibrodentinoma, and two ameloblastic fibrosarcomas. The epithelial components of the tumors were separated from the mesenchymal by laser microdissection in most of the cases. We also searched for odontogenic pathology inPrkar1a+/−mice.PRKAR1AmRNA/protein expression was decreased in the benign mixed odontogenic tumors in association with LOH at markers around thePRKAR1Agene. We also detected a missense and two synonymous mutations along with two 5′-UTR and four intronic mutations in mixed odontogenic tumors.Prkar1a+/−mice did not show evidence of odontogenic tumor formation, which indicates that additional genes may be involved in the pathogenesis of such tumors, at least in rodents. We conclude that thePRKAR1Agene and its locus are altered in mixed odontogenic tumors.PRKAR1Aexpression is decreased in a subset of tumors but not in all, andPrkar1a+/−mice do not show abnormalities, which indicates that additional genes play a role in this tumor's pathogenesis.

Ameloblastic Fibrodentinoma: Report of a Rare Case

ABSTRACT Aim This is to report a rare case of ameloblastic fibrodentinoma (AFD), including detailed history, histopathologic as well as radiographic findings. Her condition, a mixed odontogenic tumor, has rarely been reported in publications. We also included the gist of theories put forward regarding the histogenesis of this lesion. Background AFD is a rare and controversial entity; it boasts a variety of classifications and terminology based on its unique biological nature as well as histopathological features. Case description The patient was a 13-year-old girl with a chief complaint of central unerupted tooth on the left mandible. Cone beam computed tomographic images revealed a mixed pericoronal and multilocular lesion surrounding the crown of the aforementioned tooth, displacing it apically to a large extent. Conclusion It is important to differentiate AFD from other benign mixed odontogenic tumors with similar radiographic appearance because of different therapeutic approaches in some of these tumors. Clinical significance From the clinical point of view, it is of paramount significance for dental practitioners to assess any delayed tooth eruption (more than 6 months and in comparison with its counterpart on the opposite side) radiographically to ascertain or rule out any such similar lesions. How to cite this article Salehinejad J, Langaroodi AJ, Shahakbari R, Yazdani N. Ameloblastic Fibrodentinoma: Report of a Rare Case. J Contemp Dent Pract 2013;14(3):548-551.

Giant complex odontoma of the anterior mandible: report of case with long follow up

This paper describes an exceptional case of an enormous complex odontoma affecting the mandibular symphysis of a 9-year-old boy. Because of its dimensions, the lesion produced cortical bone expansion, dental displacement and impactation, which are clinical signs very seldom described for odontomas. The lesion was surgically excised in a conservative way using an intraoral approach with local anesthesia. After 7 years of follow up, all teeth had erupted and the mandibular bone healed totally. Because of its radiographic mixed radiolucent and radiopaque appearance and its expansive growth, it is imperative to make the differential diagnosis of giant complex odontoma for other more aggressive mixed odontogenic tumors, such as ameloblastic fibro-odontoma, odotoameloblastoma and cystic calcified odontogenic tumor. Conservative approach appears to be indicated in the treatment of such lesions.