Conventional ameloblastoma

Previously known as solid/multicystic ameloblastoma. Usually presents with multiple large cystic areas.

Unicystic ameloblastoma

Ameloblastoma with a single cyst cavity account for around 10% of ameloblastomas. Present in younger patients in their second and third decades of life, often in relation to unerupted third molar.^[8]

Metastasising ameloblastoma

Histologically atypical ameloblastoma can, rarely, lead to metastasis, usually in the lung. 'Metastasis' look histologically identical to the primary tumour and are benign in nature.^[8]

Peripheral ameloblastoma

The peripheral subtype composes 2% of all ameloblastomas.^[1]

Solid structure

Solid areas contain fibrous tissue islands or epithelium that interconnect through strands and sheets. The epithelial cells tend to move the nucleus away from the basement membrane to the opposite pole of the cell. This process is called reverse polarization. Two main histological patterns most often occur: follicular and plexiform. Other less common histological variants include acanthomatous, basal cell, and granular cell patterns.^[8]

Cystic structure

Large cysts up to a few centimetres in diameter can be found. In follicular type, cysts develop in the stellate reticulum and in the plexiform type, cysts are caused by degeneration of connective tissue stroma.^[8]

Desmoplastic ameloblastoma

A distinctive histological variant of conventional ameloblastoma. Found in near equal frequencies in both maxilla and mandible. Resemble a fibro-osseous lesion with no obvious ameloblasts whilst dominated by dense collagenous tissue (desmoplastic).^[8] In one center, desmoplastic ameloblastomas represented about 9% of all ameloblastomas encountered.^[12] A systematic review showed a predilection for males and predominance in fourth and fifth decades in life. 52% desmoplastic ameloblastomas showed mandibular involvement, with a tendency to anterior region. Majority of tumours were found to have ill-defined margins radiographically.^[13]

Differential diagnosis

• Keratocystic odontogenic tumour
• Central giant-cell granuloma
• Odontogenic myxoma

Surgical resection

The aim of treatment and surgery is to remove the entire tumour with a margin of surrounding tissue (block resection) for a good prognosis.^[10] Preferable removal includes 10mm of normal bone around the neoplasm. Larger ameloblastomas can require partial resection of the jaw bone followed by bone grafting.^[8] There is evidence that the treatment of conventional ameloblastoma is best done by bone resection.^[16] A systematic review found that 79% of desmoplastic ameloblastoma cases were treated by resection.^[13]

Enucleation

Smaller mandibular neoplasms have been enucleated where the cavity of the tumour is curetted, allowing preservation of the bone cortex and the lower border of the mandible. Although, recurrence rate for this type of treatment is higher. Unicystic ameloblastomas—called intraluminal unicystic or plexiform unicystic ameloblastomas can be enucleated, as the epithelium is only limited to the inner cyst wall and lumen.^[8]

Radiation and chemotherapy

Radiation is ineffective in many cases of ameloblastoma.^[1] There have also been reports of sarcoma being induced as the result of using radiation to treat ameloblastoma.^[17] Chemotherapy is also often ineffective.^[17] However, there is some controversy regarding this^[18] and some indication that some ameloblastomas might be more responsive to radiation that previously thought.^[19][5]

Follow-up and recurrence

Persistent follow-up examination including radiographs is essential for managing ameloblastoma.^[20][8] Follow-up should occur at regular intervals for at least 10 years.^[21] Follow up is important, because 50% of all recurrences occur within 5 years postoperatively.^[1]

Recurrence is common, although the recurrence rates for block resection followed by bone graft are lower than those of enucleation and curettage.^[22] Follicular variants appear to recur more than plexiform variants.^[1] Unicystic lesions recur less frequently than "non-unicystic" lesions.^[1] A low recurrence rate of around 10% can be seen in unicystic ameloblastomas.^[8] Recurrence within a bone graft (following resection of the original tumor) does occur, but is less common.^[23] Seeding to the bone graft is suspected as a cause of recurrence.^[20] The recurrences in these cases seem to stem from the soft tissues, especially the adjacent periosteum.^[24] Recurrence has been reported to occur as many as 36 years after treatment.^[25] To reduce the likelihood of recurrence within grafted bone, meticulous surgery^[23] with attention to the adjacent soft tissues is required.^[24][20]

Molecular biology

BRAF V600E gene and SMO gene mutations have been found in ameloblastomas. V600E mutation is also seen in other malignant and benign neoplasms, which activate the MAP kinase pathway required for cell division and differentiation but is the most commonly seen mutation in ameloblastoma.^[8][7] 72% of BRAF mutations are found in the mandible.^[7] A recent study discovered a high frequency of BRAF V600E mutations (15 of 24 samples, 63%) in conventional ameloblastoma. These data suggests drugs targeting mutant BRAF as potential novel therapies for ameloblastoma.^[26]

SMO mutations lead to the activation of the hedgehog pathway giving similar results as V600E but is less frequently seen.^[8] 55% of SMO mutations are found in the maxilla.^[7]

Evidence shows that suppression of matrix metalloproteinase-2 may inhibit the local invasiveness of ameloblastoma, however, this was only demonstrated in vitro.^[27] There is also some research suggesting that α₅β₁ integrin may participate in the local invasiveness of ameloblastomas.^[28]