Cemento-Osseous Dysplasia With a NOTCH4 Mutation: a Case Report

Purpose Cemento-osseous dysplasia (COD) is a benign fibro-osseous lesion of the jaw that poses diagnostic challenges due to overlapping features with other entities, particularly cemento-ossifying fibroma (COF). While recent studies have identified mutations in the RAS-MAPK pathway in COD, its broader molecular profile remains poorly understood. Here, we report a case of COD harboring a novel NOTCH4 mutation, expanding the spectrum of genetic alterations associated with this lesion. Methods We present a case of a 32-year-old woman with an incidental lesion in the right mandibular angle. The lesion was surgically enucleated and analyzed histologically. Next-generation sequencing (TSO500 panel) was performed. Results Radiographic evaluation showed a lesion without sharp demarcation. Histopathology shows a fibro-osseous lesion with interconnected bony trabeculae lacking osteoblastic rimming, consistent with COD. Molecular analysis detected a NOTCH4 mutation. Conclusion This case identifies a novel NOTCH4 mutation in COD, suggesting possible involvement of the Notch signaling pathway in its pathogenesis. Incorporating molecular profiling into the diagnostic workflow may aid in distinguishing COD from COF and enhance our understanding of fibro-osseous lesions of the jaw.