Benign epithelial odontogenic tumors

2025-11-18 Paola Dal Cin, PhD Affiliation

1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Keywords

{BRAF} p.V600E mutations, ameloblastoma

Classification

Definition

Odontogenic and maxillofacial bone tumors	Genetic marker(s)
Benign epithelial odontogenic tumors
Adenomatoid odontogenic tumor (AOT)	Most (~70%) of sporadic adenomatoid odontogenic tumours (AOT) have been identifed to carry KRAS p.G12V and p.G12R mutation. ¹ Patients with Schimmelpenning syndrome OMIM:163200 caused by postzygotic RAS mutations show multiple AOTs.²
Squamous odontogenic tumor (SOT)	Because of histologic overlap, AOT has often been overdiagnosed as ameloblastoma and squamous cell carcinoma. A massive DNA sequencing revealed an exceptional evolution with RET and POLE mutations (at the initial and in the relapse tumors) and variants mutation in NSD1 (at the initial) and in BRCA2 (in the relapsed), and loss of ALK and gain of CDKN1B and MAP2K only in the relapsed specimen. ³
Calcifying epithelial odontogenic tumor (CEOT)	Different mutations PTCH1,AMBN, PTEN, CDKN2A, JAK3 and MET have been reported, mainly occurred in only one case each.⁴ Single-gene investigations revealed PTCH1 and/or AMBN mutations.⁵
Ameloblastoma (AM)	BRAF p.V600E mutations have been found in all types of ameloblastoma (unicystic, extraosseous, peripheral, conventional} ⁶ Mutations in other components of the MAPK pathway have also been reported in ameloblastoma, e.g., KRAS ,NRAS ,HRAS, FGFR2 and EGFR as well as non-MAPK pathway mutations,e.g., SMO, SMARCB1, PIK3CA, among others, in a small proportion of lesions, tending to co-occur with the MAPK pathway mutations. ⁷ Interestingly, ameloblastomas with BRAF mutations are predominantly (96%) located in the mandible and ameloblastomas with SMO mutations are predominantly found in the maxilla (85%).⁸
Adenoid ameloblastoma (AdAM)	Locally aggressive odontogenic neoplasm mainly occurs in the maxilla or mandible. Alterations in the WNT pathway include CTNNB1 hotspot mutations, and APC, SMURF1, and/or NEDDL4LI alterations. ⁵KRAS p.G12V/R or BRAF p.V600 mutations are absent in adenoid ameoblastoma. ⁹
Metastasizing ameloblastoma	Since histological differentiation from non-metastasizing ameloblastoma is not possible, the diagnosis of metastasizing ameloblastoma can be made only retrospectively, when metastasis has occurred. ^8,10

Article Bibliography

Reference Number	Pubmed ID	Last Year	Title	Authors
1	30643167	2019	KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features.	Coura BP et al
2	31402313	2020	Multiple adenomatoid odontogenic tumors in a patient with Schimmelpenning syndrome.	Chaves RRM et al
3	39273494	2024	Exceptional Evolution of a Squamous Odontogenic Tumor in the Jaw: Molecular Approach.	Alonso-Juarranz M et al
4	29127140	2018	Cancer genes mutation profiling in calcifying epithelial odontogenic tumour.	de Sousa SF et al
5	37278887	2023	Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Odontogenic Tumors: Have We Achieved an Evidence-Based Classification.	Magliocca KR et al
6	30216733	2019	The Mutational Profile of Unicystic Ameloblastoma.	Heikinheimo K et al
7	35048058	2021	The Molecular Pathology of Odontogenic Tumors: Expanding the Spectrum of MAPK Pathway Driven Tumors.	Guimarães LM et al
8	36127985	2022	Ameloblastoma: An Updated Narrative Review of an Enigmatic Tumor.	Ghai S et al
9	34549835	2021	Adenoid ameloblastoma with dentinoid is molecularly different from ameloblastomas and adenomatoid odontogenic tumors.	Coura BP et al
10	33394372	2021	Metastasizing Ameloblastoma: A 10 Year Clinicopathological Review with an Insight Into Pathogenesis.	Pandiar D et al

External Links

Citation

Paola Dal Cin, PhD

Benign epithelial odontogenic tumors

Atlas Genet Cytogenet Oncol Haematol. 2025-11-18

Online version: http://atlasgeneticsoncology.org/solid-tumor/209341/benign-epithelial-odontogenic-tumors