Odontogenic sarcomas : clinicopathologic analysis and immunohistochemical expression of BRAF and SOX9 in a multicenter series of 10 cases

Abstract

INTRODUCTION : Odontogenic sarcomas (OS) are rare malignant mixed odontogenic tumors featuring benign epithelial and malignant ectomesenchymal components. MATERIALS AND METHODS : Ten OS cases from seven Oral and Maxillofacial Pathology services were retrospectively reviewed (2000–2024), including clinical, radiographic, histopathologic, and immunohistochemical data (BRAF p.V600E and SOX9). RESULTS : Five female and five male patients, with a mean age of 30 years (range: 9–72 years), presented with mandibular tumors, all as aggressive, ill-defined radiolucencies. Eight patients reported a prior diagnosis of a benign mixed odontogenic tumor (mean interval: 3.6 years). Six patients underwent wide surgical resection; one experienced recurrence within two years and showed high-grade transformation. Histopathologic examination revealed benign odontogenic epithelium within malignant ectomesenchyme with hypercellularity, pleomorphism, and increased mitotic figures. Rare features included ghost cells, microcystic degeneration, vacuolated morphology, and high-grade transformation. BRAF p.V600E was positive in 60% of the mesenchymal component. SOX9 was diffusely expressed in both epithelial and mesenchymal components, with reduced staining in the case with high-grade transformation. CONCLUSION : OS primarily affects young adults and often arises from pre-existing benign mixed odontogenic tumors. Despite variable histology, the biological behavior of the tumors remains consistently aggressive. BRAF p.V600E and SOX9 may aid diagnosis. Vigilant follow-up of patients diagnosed with benign mixed odontogenic tumors is essential, particularly within four years post-surgery. Multicenter studies are warranted to better understand the pathogenesis of OS and support the development of targeted therapeutic strategies.