Ameloblastomas usually are asymptomatic until the patient notices intraoral or facial swelling. Patients often present with progressive maxillary or mandibular expansion and facial asymmetry. Pain and altered sensation are uncommon. Patients may complain of a change in bite and loose teeth. Smaller tumors are usually detected first on routine dental radiographic exams. Untreated tumors can grow to massive proportions and cause facial deformity, as exhibited, especially in third world countries where patients can go for long periods before seeking treatment or having access to care.

Tumor and characteristics are assessed using the patient’s history, clinical exam, and imaging, most commonly computed tomography (CT). On CT scan, ameloblastomas appear as radiolucent (radiographically dark) lesions of the maxilla or mandible, often with multilocular or “soap-bubble” appearance, bony expansion and tooth root resorption. They may also be associated with unerupted teeth. A definitive diagnosis of ameloblastoma is with a surgical biopsy, which shows characteristic histologic findings. It is essential to differentiate the entity from a primary intraosseous squamous cell carcinoma.

The World Health Organization (WHO) classified malignant ameloblastoma into two types[3]:

1. Metastasizing ameloblastoma
   • Histologically similar to benign ameloblastoma but shows metastatic spread to distant sites
2. Ameloblastic carcinoma
   • Shows malignant features on histology
   • Can be further subdivided into two subtypes:
     • Primary ameloblastic carcinoma: arises de novo (from Latin meaning "anew")
     • Secondary ameloblastic carcinoma: the eventual result of malignant transformation of a previously diagnosed benign ameloblastoma

Mural and solid ameloblastomas are treated with complete surgical excision with normal bone margins at a minimum of five to fifteen mm, though ten mm margins are most common. Reported recurrence rates are up to 70%, with incomplete resection being the most common reason for the high recurrence rate. Enucleation and curettage, cryotherapy and marsupialization have all been used to treat ameloblastomas; however, these modalities are not curative and are not standard of care now.

Ameloblastic carcinoma treatment is generally via surgical resection with 2 to 3 cm margins. Concurrent chemoradiotherapy is an option after resection for positive margins or perineural invasion. In malignant ameloblastoma, surgical resection with 1 to 2 cm margins is usually the treatment modality of choice, and no chemotherapy or radiotherapy is generally required.[4]

Since malignant ameloblastoma is typically a slow-growing tumor, more active treatment approaches such as chemo or radiotherapy may not be necessary. Close patient follow-up for a minimum of five years is necessary to monitor for recurrence.

Practitioners follow the most current recommendations from the American Joint Committee on Cancer and the National Comprehensive Cancer Network for more detailed treatment modalities, indications for neck dissections, chemo, and radiotherapy, etc.

It is difficult to differentiate benign ameloblastoma from malignant ameloblastoma on histology alone as it can look benign on histology but be clinically invasive or even metastasize. Benign ameloblastoma is histologically identical to malignant ameloblastoma but has no metastases. However, malignant variations are extremely rare, with only approximately 30 cases of malignant ameloblastoma in the literature, and about several hundred cases of ameloblastic carcinoma. 

Ameloblastic fibroma may share the same features histologically, such as small cords and islands of ameloblastic epithelium that's just two cells thick containing dense collagenous stroma which is often immature. It can also occasionally contain cementum or dentin production as well as stellate reticulum. The main feature of ameloblastic fibroma is that the stroma is more primitive and it should not metastasize. 

Primary squamous cell carcinoma of the lung and metastatic disease in the lung that has spread will have histologic features of malignancy but no other features of ameloblastoma (no polarization, no peripheral palisading, no stellate cells, etc.).

Practitioners follow the most current recommendations from the American Joint Committee on Cancer and the National Comprehensive Cancer Network for more detailed treatment modalities, indications for neck dissections, chemo, and radiotherapy, etc. These guidelines are updated annually.

Practitioners follow the most current recommendations from the American Joint Committee on Cancer and the National Comprehensive Cancer Network for more detailed treatment modalities, indications for neck dissections, chemo, and radiotherapy, etc. These guidelines are updated annually.

There is a Phase 2 study at Stanford University titled A Pilot Study of Dabrafenib and Trametinib for Patients With BRAF Mutated Ameloblastoma which studies dabrafenib and trametinib in treating patients with ameloblastoma and a specific mutation in the BRAF gene. The study authors believe Dabrafenib and trametinib may halt the growth of tumor cells by blocking enzymes needed for cell growth. The study is currently the only one looking at a specific treatment for ameloblastomas. It started in July 2017 and is currently recruiting. The study has an estimated completion date of August 2020, and they are expected to enroll 17 participants.

During the study, patients receive dabrafenib orally (PO) two times daily every 12 hours and oral trametinib 2 mg daily for 6 weeks in the absence of disease progression or unacceptable toxicity. Patients with disease determined to be not amenable to resection will indefinitely continue dabrafenib and trametinib as long as there has been no tumor progression.

Following the completion of the study therapy, patients are followed up for at least 4 weeks. 

It is worth noting that this study addressed ameloblastomas, not a malignant variation.

Treatment completion will be by a surgeon trained in head and neck surgery, typically an oral and maxillofacial surgeon, otolaryngologist, plastic surgeon, or oncologic surgeon. Often, case planning can include either immediate or delayed reconstruction. Treatment planning is critical, especially when involving teeth, as extractions of teeth in the lesion are often completed and permitted to heal before access through the neck, thus preventing communication with the oral cavity and associated bacteria. 

Currently, there is no staging system for ameloblastoma due to the absence of prospective studies for this very rare disease. 

Unfortunately, malignant ameloblastoma is too rare to estimate its prognosis. Due to its slow-growing nature, the malignancy may not occur for up to 10 years after initial resection of benign ameloblastoma. 

The complications of malignant ameloblastoma are usually due to its local invasiveness or distant metastatic spread. In terms of local complications, it can lead to progressive maxillary and mandibular distortion leading to deformity, pain, and malocclusion.

Consider consultation with a dentist, OMS, and/or ENT surgeon.

It is essential to educate patients on the usually benign nature of ameloblastomas, but a high rate of recurrence. Keeping patients informed of the importance of regular follow up is crucial to monitor any benign or possible malignant ameloblastoma since it is difficult to differentiate between the two histologically. 

A small percentage of ameloblastomas (two percent) are peripheral and located in the soft tissues of the oral cavity. Rarely, ameloblastomas can undergo a malignant transformation or can metastasize to distant sites such as the lymph nodes and lungs. The vast majority of ameloblastomas are the benign, but aggressive type. These patients will need surgery and life long follow up.

It is crucial to have an interprofessional team approach to the management of malignant ameloblastoma. It is vital to have oral-maxillofacial surgeons and plastic surgeons involved in any possible reconstruction needs after surgical excision. Head and neck trained surgeons familiar with the complete surgical excision of malignant ameloblastoma are central to complete tumor excision. Speech-language pathologists and voice therapists are important post-operatively for the management of voice and swallowing issues that may arise after surgical excision.

The dietitian should be involved early in the care as many patients after surgery will have trouble eating. Healing of the oral tissues can take weeks or months, and hence, consideration to enteral or parenteral feeding may be necessary. The nurses should also assess the oxygenation, breathing, and assist with suctioning the oral cavity. Aspiration is also a risk after surgery, and the patients need to have the head of the bed elevated. Also, the patients need DVT and stress ulcer prophylaxis. Since major surgery in the facial area can also result in severe aesthetic changes, a mental health nurse should counsel the patient. Finally, the pain team should have involvement as postoperative pain can be significant. Pharmacist involvement comes in the form of assisting in pain management as well as those cases where chemotherapy is an option. All these professionals need to maintain open lines of communication with other providers so that interprofessional effort leads to optimal patient outcomes. [Level V]

Though radiation and chemotherapy are not the mainstem of treatment for malignant ameloblastoma, it is important to involve them in select cases where chemoradiotherapy may be of benefit. The entire team should communicate on patient care plans to ensure the best outcomes.