May 2023 – Oral Pathology

A 9-year-old boy​ presented for evaluation of a right mandibular lesion​. He denied having any pain associated with the area or neurosensory changes along the inferior alveolar nerve region​. Imaging showed a mixed radiolucent/radiopaque lesion in the right mandible angle region​. Enucleation and curettage of the posterior mandibular lesion was performed. Histologic sections show small islands of odontogenic epithelium​ surrounded by odontogenic ectomesenchyme (primitive dental papilla-like) containing dentin and enamel (Figure 1)​.

Figure 1

What is the most likely diagnosis?

  • Odontogenic myxoma
  • Odontoma
  • Ameloblastic fibroma/Fibro-odontoma
  • Ameloblastoma

The correct answer is ...

Ameloblastic fibroma/Fibro-odontoma.

Ameloblastic fibroma (AF)/Fibro-odontoma (AFO) is a benign mixed epithelial and mesenchymal odontogenic tumor. It is more commonly encountered in the first two decades of life (mean patient age is 15 years old, with 80% of lesions occurring before age 22). These lesions present with a higher frequency in the posterior mandible. Radiographically they are well-defined and corticated, usually unilocular and associated with unerupted teeth and some can have a radiolucent-radiopaque appearance (Figure 1A, arrow).

AF is associated with BRAF p.V600E mutation in 46% of cases. Histologically, the lesions are composed of an evenly hypercellular myxoid, primitive-appearing mesenchymal component, resembling the developing dental papilla. The admixed epithelial component resembles ameloblastoma and is comprised of islands, cords, and strands of bilaminar cuboidal to columnar palisaded cells surrounding areas of stellate reticulum-like tissue, reminiscent of the follicular stage of the enamel organ (Figure 1 B-C). In the 2022 WHO Classification of Tumors, lesions previously diagnosed as ameloblastic fibro-odontoma and ameloblastic fibro-dentinoma (AFD) are now mentioned in the AF and odontoma sections as histologically intermediate between AF and odontomas; however, their status is still debated. Histologically, AFO and AFD resemble AF, but they also contain dental hard tissue matrix such as dentin and enamel (Figure 1 C-D). Clinically these lesions are usually treated with curettage and have a low rate of recurrence. 

Ameloblastoma can be differentiated from ameloblastic fibroma/fibro-odontoma based on radiologic features (multilocular, corticated, radiolucent lesions with a “soap-bubble” appearance), age at time of presentation (peak incidence in the fourth and fifth decades of life), and histological characteristics including absence of the hypercellular myxoid mesenchymal component and lack of dental hard tissue matrix, such as dentin and enamel. It is important to differentiate ameloblastoma from its mimics due to its high rate of recurrence and the requirement for complete resection with negative bone margins (1 cm).

Odontomas are mixed odontogenic hamartomas, predominantly composed of dental hard tissues with small components of odontogenic epithelium and primitive mesenchyme. Developing odontomas may exhibit overlapping morphologic features with AF/AFO and correlation with clinical and imaging findings may be helpful. 

Odontogenic myxoma is composed of sparse stellate, spindled and round cells within a prominent, loose, myxoid stroma with scant collagen fibers, and occasional small rests of inactive odontogenic epithelium. The stroma is typically hypocellular and lacks the primitive appearance, as well as the ameloblastic epithelium. 


  1. WHO Classification of Head and Neck Tumours, 4th Edition, Volume 9. Edited by El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ
  2. Buchner A, Vered M. Ameloblastic fibroma: a stage in the development of a hamartomatous odontoma or a true neoplasm? Critical analysis of 162 previously reported cases plus 10 new cases. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013 Nov;116(5):598-606. PMID:24055148.
  3. P Brunner, M Bihl, G Jundt, D Baumhoer, S Hoeller. BRAF p.V600E mutations are not unique to ameloblastoma and are shared by other odontogenic tumors with ameloblastic morphology. Oral Oncol. 2015 Oct;51(10):e77-8. PMID: 26306423.
  4. Petrovic ID, Migliacci J, Ganly I, Patel S, Xu B, Ghossein R, Huryn J, Shah J. Ameloblastomas of the mandible and maxilla. Ear Nose Throat J. 2018 Jul;97(7):E26-E32. PMID: 30036443.
Photo of Veronica Ulici, MD, PhD

Veronica Ulici, M.D., Ph.D.

Fellow, Surgical Pathology
Mayo Clinic

Photo of David Schembri Wismayer, M.D.

David Schembri Wismayer, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

Anja Roden Profile

Anja Roden, M.D.

Consultant, Anatomic Pathology
Mayo Clinic
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.