Ameloblastic fibrodentinoma, ameloblastic fibro-odontoma and odontoameloblastoma: Distinct entities or a morphological spectrum?

BACKGROUND: The classification of mixed odontogenic tumors remains one of the most debated topics in oral and maxillofacial pathology. Although ameloblastic fibrodentinoma (AFD), ameloblastic fibro-odontoma (AFO), and odontoameloblastoma were historically recognized as distinct entities, their biological nature and taxonomic status have been repeatedly questioned in successive editions of the World Health Organization (WHO) Classification of Head and Neck Tumours. OBJECTIVE: To critically evaluate the current evidence regarding the classification, pathogenesis, and biological behavior of AFD, AFO, and odontoameloblastoma, and to discuss whether these lesions represent independent entities or components of a broader morphological and biological spectrum. METHODS: A narrative critical review was conducted by members of the International Consortium on Odontogenic Tumours, integrating historical, clinicopathological, radiographic, and molecular evidence, with particular emphasis on recent genomic studies and WHO classification updates. RESULTS: Emerging molecular data demonstrate recurrent alterations, particularly BRAF p.V600E mutations, in a substantial subset of AFD and AFO, supporting a neoplastic nature in at least some cases. The existence of malignant counterparts, including ameloblastic fibrodentinosarcoma and ameloblastic fibro-odontosarcoma, further challenges the concept that these lesions are purely developmental or hamartomatous. In contrast, odontoameloblastoma lacks a distinctive molecular profile and exhibits significant overlap with other odontogenic tumors, raising doubts regarding its status as a separate nosological entity. Current evidence suggests considerable biological heterogeneity among these lesions. CONCLUSIONS: AFD, AFO, and related lesions are best interpreted within a biological spectrum of mixed odontogenic tumors rather than as rigidly defined entities. Future integrated clinicopathological and molecular investigations are required to refine their classification and improve diagnostic reproducibility.