Is Ameloblastoma Malignant?

What Is Ameloblastoma?

Amel means enamel (an early English word used to denote the tooth structure), and blastos (Greek) means the germ. Originally derived as a combination of these two words, the understood etiology was of the primary tumors arising from the epithelium of ectodermal origin or simply put as tumors of the ectodermal germ layer.

These tumors are locally aggressive but still benign with a nonmalignant potential (most of the time). These tumors are less common in children and occur over a broad range of patients affected from the 20-40 years age group generically. Both the male and female populations tend to be equally affected as per case reports. These tumors are much more common in the lower jaw as compared to the upper jaw and represent nearly 1 % of the odontogenic tumors in the jaw. Again, the occurrence is more in the posterior mandible than the anterior region in the lower jaw.

The fundamental concept studied as per research is that this benign tumor can behave quite aggressively and rarely has the potential and a tendency to aggravate or be associated with a malignant or cancerous lesion like malignant ameloblastoma or ameloblastic carcinoma. Though as mentioned earlier, the potential to turn cancerous or malignant remains less of a possibility, if this benign tumor is left untreated by the dental or the oral and maxillofacial surgeon, the hypothesis that it can spread to surrounding tissues and eventually be invasive in the lymphatic system and to distant systemic sites or through the bone and soft tissues remains plausible.

However, the fact is that malignant or cancerous ameloblastomas are usually less than 1 % of the ameloblastomas detected in the cases of affected individuals.

What Is the Pathophysiology of Ameloblastoma and Associated Hypothesis?

Though the pathophysiology of this tumor may not be exactly understood by researchers and clinicians alike, recent evidence has emerged regarding the genetic role of the signaling pathway called MAPK, which is activated in certain genetic mutations and disorders. However the relied theory of pathogenesis is upon the original theory of an ameloblastoma formation, the ectodermal origin theory. The ectodermal cells are mainly the ameloblasts and the odontoblasts. The ameloblasts form the enamel, and the odontoblasts form the secondary layer, dentin. The cells associated with the formation of the enamel organ, if impacted like the cell rests of Serres and the cell rests of molasses, can cause ameloblastomas mainly in the mandible region (80 % prevalence) and less commonly but definitely in the maxillary region as well (20 % prevalence).

These ectodermal cells undergo apoptosis or programmed cell death before or after tooth eruption by being an intrinsic part of the enamel epithelium. As both enamel and dentin layers form the outer surface of the crown portion of the tooth, ameloblastomas are considered definitively to be derived from the ectodermal origin and hence benign. The aggregation of odontogenic ectomesenchyme, fibrous stroma tissue, and odontogenic epithelium together makes a benign tumor as per the WHO classification and definition.

What Does the Disease’s Epidemiology Entail?

Ameloblastoma is a rare condition, occurring at a rate of 0.5 new occurrences per 1,000,000 people per year.

There are geographical differences: Africa, China, and India have higher incidences compared to the Western World.

Ameloblastomas are typically prevalent in individuals aged 30 to 60, with an average age of 36 years. The highest occurrence is observed during the fifth decade of life.

The male-to-female ratio is 1.2:1. Ameloblastomas account for 1% of all tumors occurring in the head and neck region. Ameloblastomas are the predominant kind of odontogenic(oral tumor) tumor, including around 18% of all occurrences.

How Ameloblastoma Arises Genetically?

Recent genetic studies using tumor tissue, cell lines, and transgenic mice have found several genetic changes in ameloblastoma tumors.

Studies found that the mitogen-activated protein kinase (MAPK) and sonic hedgehog (SHH) signaling pathways often have somatic and active mutations.

Ameloblastoma has changes in the BRAF, RAS, and fibroblast growth factor receptor 2 (FGFR2) genes that affect the MAPK pathway. Ameloblastoma has changes in BRAF, RAS, and FGFR2 in most cases.

What Are the Clinical Features of Ameloblastoma?

The lesions in ameloblastoma tumors, because of their slow and progressive growth, may remain undetected in the affected individuals initially and may be painless as well. However, the eventual clinical features of signs and symptoms that distinguish it are,

• Non-tender and ovoid swelling of the lower or upper jaw that slowly enlarges in size.
• Facial asymmetry.
• Tooth mobility or exfoliation pain.
• Paresthesia or numbness of the jaw.
• Inability to bite correctly (deviation from the normal occlusion leading to incorrect bite).
• Ill-fitting dentures (due to the localized lesion causing a displacement).

What Are the Types of Ameloblastoma?

Ameloblastoma is mainly classified based on cell origin and histopathologic observations.

As per cell origin, it is classified mainly into four types:

1. Solid/multicystic.
2. Extraosseous/peripheral.
3. Desmoplastic ameloblastoma.
4. Unicystic.

As per histopathology, it is classified into six types, with the follicular pattern of ameloblastoma type having the highest rate of recurrence as opposed to the acanthomatous type with the least recurrence rate.

1. Follicular.
2. Plexiform.
3. Acanthomatous.
4. Basal cell.
5. Granular.
6. Desmoplastic.

What Are the Radiological Findings of Ameloblastoma?

Radiographically, these tumor lesions are radiolucent in nature, cystic in appearance with a multilocular pattern, and maybe expansive. The cortical bone plates may be thinned in the affected region. Displacement of unerupted teeth and root resorption of adjacent teeth in the area due to the localized invasiveness of the tumor with cortical bone erosion may be other observable features.

How Is Ameloblastoma Treated?

1. Radiological investigations like CT (computed tomography) and MRI (magnetic resonance imaging) or CBCT (cone beam computed tomography) are ideal for the detection of ameloblastomas. The dental surgeon may notice these features in a routine OPG (orthopantomography) X-ray.

2. Surgical resection is the main treatment strategy for managing ameloblastoma. However, conservative excision treatment may be ineffective in these cases as the recurrence rates of the lesion tend to be high.

3. Surgical resection of the tumor with wide margins or, in severe cases, segmental mandibulectomy may be recommended by dental or maxillofacial surgeons for malignant ameloblastomas as well; because of the generally slow nature, radiotherapy or chemotherapy may not be indicated by the dental surgeon unless the progression is severe to the lymphatics or organ systems.

4. The main challenge for surgeons in this condition is to reconstruct the defect, which is usually done in the same sitting after the resection of tumor-free tissue transfer (making multiple surgical flaps available at the recipient site, that is transplantation at the recipient site). It is a novel concept that has gained recent advances in the area of reconstruction microsurgery.

5. Reconstruction of the mandibular defects is essential to restore both esthetics and functionality in the patient, and free tissue transfer is an option that can be considered for the residual defect to be filled.

6. Patient follow-up from 1-yearly to 5-yearly is mandatory for studying the healing of the surgical area and for monitoring the recurrence.

When Should One Seek Medical Attention From a Doctor?

If the patient has jaw swelling, pain, or any other issues related to dental health, it is advisable to consult with the dentist or healthcare practitioner.

Conclusion:

The propensity of the ameloblastomas may be initially slow but aggressive. Once it becomes locally invasive what makes this condition clinically challenging? Also, due to the high recurrence rates, the lesions require not only surgical excision but also acceptable reconstruction of the jaw defects for achieving long-term success in these patients.