Benign fibro-osseous lesions of the cranio-maxillofacial bones: an updated review with special emphasis on molecular pathogenesis

Background: Benign fibro-osseous lesions (BFOLs) are a heterogeneous group of bone-forming pathologies characterized by replacement of normal bone with fibrocellular stroma and mineralized tissue. Their overlapping clinical, radiological, and histopathological features often complicate diagnosis. Objective: This review summarizes the clinicopathologic characteristics and recent molecular insights of BFOLs to enhance diagnostic accuracy and classification. Approach: A narrative review of English-language literature available in electronic databases upto 2025 was performed, focusing on key clinical, radiologic, histologic, and molecular findings of BFOLs. Findings: BFOLs encompass bone dysplasias including fibrous dysplasia and segmental odontomaxillary dysplasia, ossifying fibroma, and cemento-osseous dysplasia, each showing distinct biological behavior. Molecular studies have revealed GNAS mutations in fibrous dysplasia and HRPT2 alterations in ossifying fibroma, providing clues to their pathogenesis. Conclusion: Integrating molecular data with clinicopathologic assessment refines diagnosis, prevents misclassification, and supports more precise management of BFOLs.