Rethinking Ameloblastic Fibroma and Fibro-odontoma: A Serie of 6 Cases and Reclassification Proposal

Abstract

Purpose: The classification of mixed odontogenic tumors-specifically ameloblastic fibroma (AF), ameloblastic fibro-odontoma (AFO), and odontoma-remains controversial. The current WHO classification emphasizes the presence of dental hard tissues but overlooks the distinction between aberrant inductive activity and maturation resembling normal odontogenesis. This has led to diagnostic ambiguity and inconsistent management strategies. This study aims to propose a biologically grounded reclassification based on histological, developmental, and molecular criteria.

Methods: We conducted a conceptual reassessment of AF, AFO, and odontoma, using six cases from our pathology archives. Histological slides were reviewed with focus on the type and organization of mineralized tissue (tubular dentin, osteodentine, enamel) and its epithelial-mesenchymal context. Clinical and radiological data were evaluated, and BRAF V600E mutation status was retrieved when available. A targeted literature review was performed to integrate findings on histology, genetic alterations, and malignant transformation risk.

Results: Two distinct lesion types were identified: (1) Ameloblastic fibroma with aberrant inductive activity, showing irregular osteodentine and enameloid deposits without odontoblast differentiation, harboring BRAF mutations; and (2) odontomas, characterized by mature tubular dentin and enamel formation, indicating a hamartomatous nature, despite significant clinical growth. Historical descriptions support this biological dichotomy, emphasizing the difference between aberrant inductive activity and processes resembling normal odontogenesis.

Conclusion: We propose abandoning AFO as a distinct diagnostic entity. Instead, lesions could be classified based on the presence of organized, mature dental hard tissues. AF with aberrant inductive activity represents a benign neoplasm with low malignant potential, while odontoma is a hamartomatous lesion sometimes with large growth capacity but no malignant risk. This binary classification would align histological criteria with biological behavior, integrate molecular data, and restore diagnostic clarity. The validity of this framework should be investigated in future cohorts.

Keywords: Ameloblastic fibro-odontoma; Ameloblastic fibroma; BRAF mutations; Epithelial-mesenchymal interaction; Odontogenic tumors; Odontoma.