This case report describes an AFO with an FGFR1 mutation. FGFRs (Fibroblast Growth Factor Receptors) are crucial in cellular functions like proliferation, differentiation, and survival by regulating pathways such as RAS-ERK/MAPK. When Fibroblast Growth Factor (FGF) binds to FGFR, it initiates a cascade activating key proteins—RAS, RAF (e.g., BRAF), MEK, and ERK—promoting cell growth and differentiation [6]. Mutations in FGFR and BRAF disrupt this pathway, contributing to tumorigenesis in various cancers [7].

The molecular pathogenesis of odontogenic tumors is not fully understood; however, the MAPK/ERK pathway is known to play a role in a subset of tumors with ameloblastic features, such as ameloblastic fibroma, AFO, and ameloblastoma [3, 4, 8]. Notably, BRAF V600E mutations are frequently identified in these tumors, and FGFR mutations have also been reported in ameloblastomas [7, 9, 10]. Therefore, it is unsurprising that, besides BRAF, an FGFR mutation has now been identified in AFO.

The classification of AFO has evolved over time. Previously, it was classified as a distinct entity among mixed odontogenic tumors [11]. However, in the 4th edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors, published in 2017, AFO was redefined as part of the continuum of developing odontomas [1]. This perspective was reaffirmed in the 5th edition published in 2022, emphasizing that AFO is not a neoplastic entity but represents the early stages of odontoma development [12].

There may be a grey area in which certain tumors cannot be definitively classified as either complex odontomas or AFOs. When a tumor exhibits features of a complex odontoma but also contains focal components resembling dental papilla– morphologically similar to ameloblastic fibroma– differentiating between a complex odontoma and an AFO can be challenging. However, in cases where tumors exhibit pronounced ameloblastic fibroma-like features and distinct hard tooth-like formations (like complex odontoma), a diagnosis of AFO should probably be rendered. Some cases may fall within a spectrum between well-defined odontogenic entities. However, the presence of BRAF or FGFR mutations could suggest that the tumor aligns more closely with an AFO rather than a (developing) complex odontoma.