Mixed odontogenic tumors: A review of the clinicopathological and molecular features and changes in the WHO classification

BACKGROUND: Ameloblastic fibromas and ameloblastic fibrosarcomas are rare odontogenic tumors, and controversy exists in the classification of cases presenting hard-tissue production: Ameloblastic fibrodentinoma (AFD) and ameloblastic fibro-odontoma (AFO). These cases are currently considered “developing odontomas” (hamartomatous lesions). AIM: To analyze the clinicopathologic features of these lesions and discuss the changes in the 2017 World Health Organization classification. METHODS: An electronic literature search was performed in the PubMed/MEDLINE database. An electronic search of the English language literature was performed and last updated in September 2020 in the PubMed/MEDLINE database using the following terms: “ameloblastic fibroma”, “ameloblastic fibrodentinoma”, “ameloblastic fibro-odontoma”, “ameloblastic sarcoma”, “ameloblastic fibrosarcoma”, “ameloblastic fibrodentinosarcoma”, “ameloblastic fibroodontosarcoma” and “odontogenic carcinosarcoma”. The inclusion criteria were odontogenic tumor series, case reports and systematic reviews that provided sufficient clinical, radiological and microscopic documentation to confirm the diagnosis. RESULTS: The database search strategy resulted in 947 papers. Articles focusing on other topics, articles that were not in English, duplicate articles, and articles without fulfilling the inclusion criteria were excluded. Finally, 96 publications were included in this review to describe and discuss the main features of the searched entities. Several aspects of AFO and AFD, such as biological behavior, age of occurrence, amount of hard tissue, and potential for malignant transformation into odontogenic sarcomas, support the neoplastic nature in most of the reported cases. Considering the clinical, radiographic, histopathological and molecular characteristics of odontogenic lesions with hard tissue production, we suggest that these types of lesions should continue to be recognized as odontogenic tumors by maintaining the classically used terms. CONCLUSION: This recommendation will be relevant for future clinical, microscopic, and molecular studies to better understand the biology of these interesting odontogenic tumors.