Odontogenic tumors (OTs) are rare tumors of the jaws that arise from remnants of the tooth forming apparatus. They comprise a heterogeneous group of benign and malignant lesions.

Benign odontogenic tumors are classified into epithelial, mesenchymal, and mixed epithelial/mesenchymal tumors based on the odontogenic tissue they mimic. ¹

Malignant odontogenic carcinomas are rare and include ameloblastic carcinoma, sclerosing odontogenic carcinoma, clear cell odontogenic carcinoma , ghost cell odontogenic carcinoma and primary intraosseous carcinoma NOS . They arise either de novo from elements of the tooth-forming apparatus or as a malignant transformation of a pre-existing oral lesion such as a benign OT or cyst. ^2-4

Most odontogenic tumors carry mutations affecting the MAPK/ERK, WNT/β-catenin, and Sonic Hedgehog signaling pathways. ^1,5,6 MAPK/ERK signaling pathway mutations seen in odontogenic tumors include mainly BRAF,and mutually exclusive and less common KRAS,NRAS, HRAS, FGFR2 and EGFR. ⁷

The BRAF p.V600E mutation emerged as a molecular signature for ameloblastomas and has also been shown to be frequent in other tumors with ameloblastic differentiation, occurring exclusively in the epithelial, but not in the stromal component .⁸ Notably, BRAF p.V600E is also detected in ameloblastic carcinoma, but at a lower frequency than in its benign counterpart, but not in adenoid ameloblastoma which instead harbours CTNNB1 (β-catenin gene) mutations.