- Nests and strips/trends of ameloblastic epithelium (similar to ameloblastoma), closely intermingled with viable cellular stroma
- Ameloblastic areas show palisaded columnar epithelium with central stellate epithelium. Columnar epithelium shows reverse polarity, due to location of nucelli away from basement layer, so creating subnuclear empty space.
- Stroma made up of loose collagenised hypocellular area as well as cellular spindle fibroblastic and stellate cells of primitive mesenchyme
- Occasional foci shows squamous metaplasia in ameloblastic epithelium
Points of Pathoclinics:
- Slow growing painless benign tumor, majority occurs in adolescent and young, usually first two decade of life.
- Radiology shows unerupted tooth with radiolucent tumor with smooth border
- Conservative treatment like curettage and enucleation has high chances of recurrence, and some have chances of malignant transformation while radical surgery/wide resection has very less chances .
- Ameloblastic Fibroma is usually circumscribed and not infiltrate into adjacent bony trabeculae.
- High proliferative activity without atypia and infiltration can be seen in ameloblastic Fibroma and such cases have high probability of recurrence and rarely malignant transformation. Evaluation with Ki-67 and Mib-1 can be helpful.
- In contrast to ameloblastic fibroma, ameloblastoma is common in middle aged people around 35-55 years group. Multi-locular cystic/soap bubble and honey comb looks on radiology. Classic histology shows nests and strands of ameloblastic epithelium, consists of little hyperchromatic palisaded columnar epithelium along with central loose stellate epithelium. Variable degree of cystic changes, collagenized stroma, squamous metaplasia is seen.
- BRAF V600E mutation is activator of the downstream RAS/RAF/MEK/ERK-MAPK signaling pathway, which very common in ameloblastoma, also seen in ameloblastic Fibroma. It is not seen in other odontogenic tumors. These mutation is somatic and not germline origin. BRAF V600E mutation has diagnostic and prognostic implication, also useful to initiate the targeted therapy with vemurafenib and others.
- Mutated BRAF V600E is common in young age with mandible involvement while Wild type-BRAF is common in old age and maxillary involvement.
- Molecular detection of BRAF V600E and VE1 immunohistochemistry shows 100% concordance. so, VE1 immunohistochemistry can be useful for diagnosis.
- Presence of mineralized tooth /odontoma (dental hard tissue) structure, favors designation of ameloblastic fibro-odontoma. However, hydride tumor is also common, consisting the features of both ameloblastic fibroma and ameloblastic fibro-odontoma. Calcifying odontogenic cyst is common in association with ameloblastic fibroma and ameloblastic fibro-odontoma.
- Ameloblastic epithelium resembles dental lamina and enamel, while the mesenchyme stroma resembles the dental papilla
- Dental papilla consists of loose evenly dispersed bland fibroblasts and stellate cells in a myxoid background, surrounded by odontoblast. Scattered odontogenic rest can be seen.
- Other differential is odontogenic myxoma, which contains scattered fibroblastic cells with mild atypia only, floating in abundant myxoid matrix, which infiltrate into the bony trabeculae.
- Malignant variant, ameloblastic fibrosarcoma shows highly cellular infiltrative mesenchymal tissue with pleomorphism and hyperchromatic nuclei and frequent mitotic figures. Some reports mentioned the evidence of epithelial dysplasia in odontogenic epithelium in such cases.
Brown NA, Rolland D, McHugh JB, Weigelin HC, Zhao L, Lim MS, Elenitoba-Johnson KS, Betz BL. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res. 2014 Nov 1;20(21):5517-26. doi: 10.1158/1078-0432.CCR-14-1069. Epub 2014 Jul 3. PMID: 24993163.