The Role of Radiotherapy in the Management of Ameloblastoma and Ameloblastic Carcinoma

Yoseph Adi K1,2

1
Faculty of Medicine, Universitas Airlangga, Surabaya 60286, Indonesia
2
Installation of Radiation Oncology; Dr. Soetomo Regional Hospital, Surabaya 60286, Indonesia
Correspondence: [email protected]; Tel. +6282136736464.

Abstract
Ameloblastoma and ameloblastic carcinoma are fairly rare and locally aggressive diseases with high recurrence rate
and potency of distant metastasis. Surgery is the treatment of choice for both tumors and adjuvant radiotherapy can be
considered in postoperative cases with poor prognostic factors, as well as inoperable and palliative cases.
Technological developments have driven advances in treatment modalities of radiotherapy. Given that radical surgery
is often not feasibly performed, radiotherapy, either by conventional techniques or IMRT, protons, or even carbon ion
radiation, still has a role to play in the management of ameloblastoma and ameloblastic carcinoma.
Keyword: ameloblastoma, ameloblastic carcinoma, radiotherapy

Introduction
Ameloblastoma comes from the word “amel” which means enamel and “blastos” which means young cells.
Ameloblastoma is a benign tumor originating from the odontogenic epithelium (Hertwig cells), accounting for about
11% of all odontogenic tumors.1 The occurrence of this tumor is caused by a failure of odontoblast cell differentiation
and disintegration of the periodontal ligament. These cells that fail to differentiate are known as epithelial cells
Malassez, which can undergo a transition into a variety of mesodermal and ectodermal cells, such as bone, fat,
cartilage, and neuron-like cells. Ameloblastoma is characterized by a slow growth, but it can grow into a large size
that can result in facial deformities, whereas ameloblastic carcinoma often has the characteristics of a more
progressive tumor growth, involvement of regional lymph nodes, as well as distant metastases. 2
The term odontogenic means that the tumor originates from the forming structures of tooth. Odontogenic tumors are
divided into tumors with mineralization (such as odontoma, odontogenic myxoma) and without mineralization (such
as ameloblastoma, odontogenic keratosis, dentigerus cyst, and radicular cyst which does not show mineralization). 3
Cusack first introduced the term ameloblastoma in his case report in 1827. Later, histopathology of ameloblastoma
was first described by Wedl in the year of 1853. It was thought that this tumor arose from the dental lamina
(cystosarcoma or adenoid cystosarcoma). Then Falkson went into more detailed explanation about this tumor in 1879.
In 1885, Malassez introduced the term adamantin epithelioma, and in 1890, Derjinsky introduced the term
adamantinoma, but the term is no longer used, because in 1930, Ivy and Churchill used the term ameloblastoma which
becomes the commonly used terminology until now.1 In 1983, Shafer introduced the term ameloblastic carcinoma. 4
Surgery is the main modality in the management of ameloblastoma, while chemotherapy is often prescribed in cases
of metastatic ameloblastoma. Radical surgery is often not feasible, due to the location of the mass that is usually
adjacent to critical structures caused by its extensive expansion.

In the era before 1950, there was a debate about the roles of radiotherapy in the management of ameloblastoma since
it used to be considered radioresistant. Few data explain the radio-responsiveness of this tumor. However, this
paradigm has increasingly undergone changes and will be discussed further in the section of the role of radiotherapy.

This review will discuss the role of radiotherapy in the management of ameloblastoma and ameloblastic carcinoma.

Epidemiology
Of all types of head and neck tumors, ameloblastoma is rare. Odontogenic tumor is the most common finding.
Ameloblastoma accounts for about 1% of all head and neck tumors and about 11% of all odontogenic tumors,
followed by other types of odontogenic tumors with lower incidence (keratinizing cystic odontogenic tumors,
odontomas, adenomatoid odontogenic tumor, odontogenic myxoma, calcifying epithelial odontogenic tumor, and
squamous odontogenic tumor).1 Ameloblastoma and ameloblastic carcinoma occur in a quite wide range of ages,
ranging from 30 - 60 years old, with a peak incidence at the third and fourth decade of life. Men and women have
similar incidence rate. Although they often occur in adulthood, they have also been reported in children. The incidence
of ameloblastoma in children ranges from 8.7% - 15%. 1,5 Giridhar, et al reported ameloblastic carcinoma in 3 pediatric
patients (aged less than 13 years old) in his systematic review of 199 cases. 6 Ameloblastoma and ameloblastic
carcinoma often have predilections in the posterior mandible (approximately 67%), especially in the third molar
region. Only about 15-20% of cases reported maxillary origin, and only about 2% of cases originated from the anterior
premolar.5,6
Etiology and Pathogenesis
The pathogenesis of ameloblastoma cannot be separated from odontogenesis. Tooth development or odontogenesis is
a complex process in which teeth are formed from embryonic cells. Primary teeth begin to form between the 6 th and 8th
week of prenatal development, and permanent teeth begin to form in the 20 th week. Odontogenesis occurs in 4 stages,
namely bud, cap, bell, and crown stages. In the 6 th week of the embryogenesis phase, mesenchymal cells thicken and
form the primary dental lamina. These cells will begin to invest in forming a tooth bud with an overlying cap. In the
20th week, tooth buds form a bell with ameloblastic cells and active odontoblasts. The ameloblastic cells then produce
tooth enamel, whereas odontoblastic cells produce dentin. This process is completed in the crown phase, when the
tooth is in final stage of development. Before the completion of odontogenesis, both of primary and secondary dental
lamina disappear. Presence of the remains of embryonic cells can become benign or malignant lesions in the future. 7

Figure 1. Odontogenesis. (Pictures illustrate several stages dental development. Pink color: oral epithelium; brown:
mesenchymal tooth; dark blue: ameloblast; light blue: odontoblast; yellow: dentin; white: enamel; red: pulp). 7

There are several theories that state there are some factors that can be the causes of these tumors, such as
histodifferentiation disorders that can act as irritating factors (e.g. extraction, caries, trauma, infection, inflammation,
or tooth eruption).8

Another causative factor, according to Ayesha et al, is suspected to be oncovirus, especially HPV and EBV viruses.
Both viruses are presumed to have a role in odontogenic tumors through changes in genetic and molecular
mechanisms. But in this case, a better understanding, particularly regarding molecular mechanisms, is still needed.
Hopefully, it can help to predict pathogenesis of odontogenic tumor and can make a way for new therapeutic
development, such as targeted therapies.9

Histopathology
In 2005, according to WHO, odontogenic tumors are classified into 2 categories based on their biological
characteristic, benign and malignant tumors. Furthermore, in 2017, the classification was made simpler. It was a
renewal of the previous classification system. 10

In 2005, ameloblastic carcinoma was categorized into primary and secondary types (intraosseous and peripheral).
However, in 2017, these tumors were classified based on morphology and their natural characteristics. Ameloblastoma
is divided into several histopathological types, such as follicular, plexiform, acanthomatous, granular, basaloid, and
desmoplastic cells. The follicular type is the most common finding, in which areas of loose neoplastic islands,
resembling columnar (palisade) shaped stellate reticulum and reverse nuclear polarity are found. 10

Both ameloblastoma and ameloblastic carcinoma have mutation in the BRAF gene (a proto-oncogen that plays a role
in sending signals within cells and cell growth), but ameloblastic carcinoma has expression of SOX2 (a transcription
factor which is important for maintaining cell renewal or pluripotency stem cells) and the Ki-67 proliferation index is
also higher than ameloblastoma.10 This appears to have an effect on prognosis, however it does not make a difference
in the course of radiotherapy treatment.
 Figure 2. (A) Ameloblastic carcinoma. Cytology overview of atypical epithelial islets with a central necrosis
component or keratinization (H&E x100). (B) Ameloblastic carcinoma showing peripheral cell palisade with reverse
nuclear polarization (H&E x200).10

Figure 3. (A) Follicular ameloblastoma. Epithelial Island with loose neoplastic islets. (B) Follicular ameloblastoma
with features of peripheral palisade.10

Figure 4. Histopathology of neck lymph nodes showing reactive lymphadenitis with infiltration of tumor cells (H&E
x400).11
Each of the histopathological subtypes of ameloblastoma has particular biological characteristics, so their prognosis
may differ. Ameloblastoma has several aggressive subtypes with high post local excision recurrence. 12
Clinical Manifestations
Clinically, ameloblastoma is usually asymptomatic, and it does not cause paresis of sensory nerve. This tumor grows
slowly, but it is able to grow in large-sized multi-lobular shapes, so that patients often come with complaints of
swelling and asymmetrical appearance of the face, caused by reactive bone deformation that results in jaw distortion.
If these symptoms are ignored, they can result in perforation of the bone, allowing the tumor to easily infiltrate the soft
tissue and further complicate surgery procedures. Patients with large tumors also often complain the presence of pain
which is usually associated with secondary infection. Other symptoms that can occur are often caused by shifting of
the teeth, resorption of root of the tooth, paresthesia if the tumor has invaded the inferior alveolar canal, and tooth
eruption failure. However, this tumor rarely causes mucosal ulceration. 1

Although histopathologically ameloblastoma is benign, it has a distinctive characteristic, that is aggressive local
invasion and distant metastatic in the metastatic ameloblastoma subtype. Besides, this tumor has a fairly high
postoperative recurrence rate which is reported to be up to 90%. 13-16 In contrast to ameloblastoma, ameloblastic
carcinoma usually has the character of a more rapid and progressive tumor growth, followed by pain due to ulceration
of the surrounding soft tissue, destruction of the cortex bone, and metastasis to the lymph nodes of the neck. 4
Incidence of neck lymph node involvement in ameloblastoma is 4% and incidence of distant metastases in the
metastatic ameloblastoma type is 2%. 5,6 The incidence of lymph node involvement of ameloblastic carcinoma is
28%,17 and the most common distant metastases involve the lungs (75%), followed by the bones, brain, and liver. The
incidence of metastases in the scalp, heart, and infra-temporal fossa have also been reported. 6
The Role of Imaging Modalities
Diagnostic radiological studies for initial tumor lesions may include plain head photo or panoramic photo. CT scan or
MRI may be used depending on the clinical state of the tumor, in terms of tumor size and suspicion of structural (both
bone and soft tissue) involvement around it. In this case, MRI is considered to be the most useful modality to
determine the characteristics of mass expansion and surgical planning. 18
 Figure 5. Orthopantomograph (panoramic photo) of a patient with ameloblastoma shows expansion of the
multilocular lesion leading to thinning of bony cortex and hemi-mandibular involvement. 11

Figure 6. Plain radiograph of the patient’s head (posterior – anterior projection) shows ameloblastoma expansion of
the multi-lobular lesion in the mandibular region with displacement of involved teeth. 11

Large lesion of ameloblastoma often appears as soap bubbles, while small lesion gives honeycomb appearance. The
clinical picture can be unilobular and well-defined without tooth eruption or multi-lobular with oral expansion and
resorption of adjacent root of tooth. 19,20 Besides the characteristics of local aggressiveness that differentiate it from
ameloblastoma, ameloblastic carcinoma often presents with an intraosseous mass accompanied by an osteolytic
process with a variable degree of dystrophic calcification. Thus, screening is needed for the possibility of distant
metastases, including the case of ameloblastoma recurrences. 5,6,21

Figure 7. CT scan of the axial section showing a multi-lobular mass with thinning of the bony cortex and perforation
in the posterior region of the ramus mandible.11

The PET scan is useful for recurrences and metastasis monitoring. Postoperative PET scan is also useful to
differentiate between postoperative fibrotic tissue and recurrent tumors. 22

Treatment
Surgery
Generally, surgery is considered the treatment of choice, especially for ameloblastoma and ameloblastic carcinoma. 23
Surgery is performed with en bloc removal. Surgical margin of 1 - 2 cm from the normal bone structure has been
approved as the safest surgical procedure to ensure disease-free survival. 5 A systematic review by Giridhar et al.,
examining the pattern of management and impact of prognostic factors on ameloblastic carcinoma in 199 cases,
suggested that a large surgical excision with a negative surgical margin was associated with increased disease-free
survival. Therefore, a radical surgery to achieve negative surgical margin must always be strived to achieve optimal
results. In other words, the surgery is carried out on the principle of wide excision and tumor-free surgical margin
(R0).6
According to the available literature, potential recurrence of ameloblastoma after wide local excision is approximately
15-25%, while post-local excision recurrence is around 65-90%. 24

Post wide local excision patients with negative surgical margin had much better progression-free survival (p = 0.000)
compared to patients undergoing incomplete resection. Comparison in progression-free survival after complete
resection at 2 and 5 years was 81.75% and 56.15%, whereas in patients with incomplete resection, progression-free
survival at 2 and 5 years were 64.91% and 38.94% respectively. 6

Neck lymph node dissection is recommended in cases with evidence of glandular involvement. However, Giridhar
reported incidence of lymph node involvement is not more than 5%, so neck lymph node dissection is not routinely
recommended yet. There is no significant difference in the aspect of progression-free survival and overall-survival in
patients undergoing prophylaxis lymph node dissection compared to patients who did not undergo prophylaxis lymph
node dissection.6

In patients with regional recurrence, surgery is recommended as a salvage therapy option. 6

Chemotherapy
Until now, chemotherapy has not become the primary treatment modality for ameloblastic carcinoma. There is very
little data available demonstrating the usefulness of chemotherapy for non-ameloblastic carcinoma metastasis. Several
studies on chemotherapy administration have been conducted in metastatic cases, including the metastatic
ameloblastoma subtype (this tumor may metastasize regardless of its benign histopathological characteristics). The
chemotherapy regimen given is Adriamycin, Cyclophosphamide, and Doxorubicin. But its benefits for patient’s
survival and quality of life have not been reported yet. Methotrexate and Leucovorin may also be considered, but the
evident benefits are still not clear.21,25

Meanwhile, another case report mentioned significant benefits regarding the administration of chemotherapy in
metastatic ameloblastic carcinoma. A case report by Cohen et al studying the administration of Pazopanib (tyrosine
inhibitor kinase) in ameloblastic carcinoma with pulmonary metastase indicated partial response results. 23,26

Several diagnostic studies reported the presence of certain gene mutations, as well as provision of targeted therapy in
the management of ameloblastoma and ameloblastic carcinoma, including recurrent and metastatic cases. Good
clinical response was reported for both, but data reporting the side effects is still lacking. 16,27 Advancement in
examination of signaling pathways and biomarker findings related to the pathogenesis of ameloblastoma is useful for
the development of targeted therapies.

Some selective MAPK (Mitogen-Activated Protein Kinase; a protein kinase that plays a role in cell regulation) works
by inhibiting the mutation of the MAPK and BRAF genes, so that they can stop uncontrolled proliferation. These
drugs include the BRAF inhibitors (Dabrafenib, Vemurafenib), and MEK inhibitors (Trametibin). Likewise, targeted
therapy has been developed to control mutations in SMO, one of them is Vismodegib. 28
Radiotherapy
In the era before 1950, there was a controversy over the role of radiotherapy in ameloblastoma, because this tumor
was considered radioresistant and there was no data that mentioned radio-responsivity for this tumor. 29 However, the
paradigm changed dramatically when mega voltage radiotherapy was being introduced after 1950.

Atkinson et al. retrospectively reviewed ten ameloblastoma patients who were irradiated and concluded that this tumor
was not purely radioresistant, thus radiotherapy modality might still have a role for this case. Several studies have
reported a correlation between the Ki-67 index and the malignant characteristics of the tumor. Aoki et al mentioned
that, although ameloblastoma tends to be radioresistant, ameloblastic carcinoma is still possibly radiosensitive.
Radiotherapy can be given in postoperative cases, inoperable tumor cases, as well as palliative cases. Although
surgery is the primary modality, in ameloblastoma, postoperative adjuvant local radiotherapy provides good tumor
control.26,27,30

In postoperative patients with poor prognostic factors, such as not tumor-free or close surgical margin, the presence of
regional lymph nodes involvement, extra-capsular extension, and perineural invasion, adjuvant loco-regional
radiotherapy is recommended. Study by Giridhar et al reported 12 patients with post-operative ameloblastic carcinoma
with poor prognostic factors receiving radiation at a dose of 66 Gy. Based on these data, progressions-free survival
was reported to reach 12 months.6,26

Mendenhall et al recommended to give radiation dose of 70 Gy in 35 fractions for post-resection ameloblastoma

patient with residual mass.31 Mendenhall et al summarized the clinical response data for ameloblastoma patients who
received radiotherapy. Dose and fractionation used were quite varied, some of which used hypofractionation regimens
in the case of gross postoperative residues. Of the 13 patients in the study, there were 5 patients who received
radiation and experienced disease-free period (no evidence of disease) in 3-5 years, 1 patient experienced local
recurrence within 3 years following definitive radiotherapy for gross tumor with a total dose of 50 Gy, 6 patients
experienced death not caused by cancer, and 1 patient had stable disease. 31
Giridhar et al reported progression-free survival at 5 years in patients who received adjuvant radiation was 59.59%,
and 50.71% respectively for patients who did not receive radiation. The result was not statistically significant and but
this may be due to the small number of samples. 6

Madhup et al reported a case of an ameloblastoma patient who underwent definitive radiotherapy with a total dose of
60 Gy. Radiation was provided with lateral opposing 2D Cobalt aircraft with 2:1 loading on the side of the face
involved and blocks on the eye and brain. Gradual mass reduction nearly achieving complete response at 2 years of
follow-up was reported.32

Jensen et al reported the use of localized carbon ionizing radiation in patients with recurrent and inoperable
ameloblastic carcinoma at a dose of 60 GyE. The target volume included CTV1 plus 3 mm margin as PTV1, without
including the surrounding critical organs (brain stem, spinal cord) and CTV2 covered all involved paranasal sinuses.
Prescription dose 44.8 GyE in 2.99 GyE/fraction on CTV2 (5 fractions per week) followed by booster dose on CTV1
at a dose of 14.9 GyE in 2.98 GyE/fraction. MRI results of follow-up at 6 weeks and 3 months post-radiation showed
no evidence of residual mass, with acute toxicity in the form of hyperpigmentation and xerostomia grade 1, and
mucositis grade 2. This is supported by literature stating the advantages of carbon therapy that can produce a very
steep dose gradient so it can deliver high doses to the tumor without involving too much of the healthy tissue nearby,
as well as the biological effective dose (BED) of the carbon ion that has been shown to be beneficial in radio-resistant
tumors.33

Figure 8. Distribution of carbon ion dose of 45 GyE/15 fraction and booster dose of 15 GyE/5 fraction. CTV2
isodoses line: orange, CTV1: red.33
A case report by Takahashi outlined the benefits of stereotactic radiosurgery as a treatment modality for ameloblastic
carcinoma. Existing clinical and experimental data mention that radiobiologists’ principles may differ when radiation
is given in a single high dose. Takahashi et al stated that stereotactic radiosurgery based on helical tomotherapy was
capable of achieving target coverage with comparable conformity index to stereotactic gamma knife-based
radiosurgery. Patients in the study have undergone two tumor resection surgeries, but further resection of the residual
mass was unachievable due to involvement of the internal carotid artery. Planning target volume (PTV) included gross
tumor volume (GTV) with an added margin of 2 mm, with a dose of 25 Gy for GTV and 20 Gy for PTV. The
maximum dose prescribed on the optic nerve and the pituitary gland was 14 Gy. Furthermore, in the follow-up period,
the patient was still alive for 19 months in the absence of recurrence. 34
 Figure 9. MRI of the tumor mass: (A) after incomplete resection with residual mass adhesion to the internal carotid
artery (pre-radiation), (B) reduction in the size of the residual mass at 4-month follow-up after radiation. 34
Purmal et al also reported on postoperative ameloblastic carcinoma patients with a negative surgical margin (2 cm)
without clear involvement of the lymph nodes, who underwent radiotherapy with a total dose of 60 Gy in 30 fractions.
Such patients did not show symptoms of recurrence, either local, regional, as well as distant metastases in 2 years. 35

Koca et al used the SIB (simultaneous integrated boost) radiation technique in recurrent ameloblastic carcinoma at
doses of 60 and 50 Gy, with CTV1 (clinical target volume) being GTV (gross target volume) plus a margin of 5 mm,
and PTV1 (planning target volume), an area which received a dose of 60 G, being CTV1 plus a margin of 3 mm.
Meanwhile, PTV2 was CTV1 plus a margin of 15 mm, which received a dose of 50 Gy. Patient experienced a partial
response 12 months after radiotherapy.36

Due to the high recurrence rate of ameloblastic carcinoma, management with surgery alone does not appear to be
beneficial. This was stated by Perera et al who treated cases of ameloblastic carcinoma with a history of multiple
recurrence after undergoing wide excision, but then the patient survived 30 months after completion of two
stereotactic gamma radiosurgery knife with tolerable toxicity and never showed recurrence in the radiation field. 37
Proton therapy is a method of giving radiation by utilizing the physical characteristics of the particle’s energy which
are different from the characteristics of the photon’s rays. In proton therapy, the term Bragg peak is known. It enables
gradual increase of the absorbed dose with deeper depth and slower speed, then in a sudden and quick moment, the
dose will go up to the breaking point and a moment later the radiation stops completely. Dionisi et al reported the
administration of definitive proton therapy for inoperable ameloblastoma with dose of 66 Gy in 33 fractions. It
resulted in a complete response shown on MRI 3 months post radiation with tolerable persistent acute toxicity, and the
patient had an excellent quality of life without evidence of clinical or radiological disease up to 18 months. 38

Figure 10. Dose distribution and dose-volume histogram. Yellow, orange, and red isodoses line represent 54 Gy, 60
Gy, 62.7 Gy, respectively.38
Brachytherapy in cases of recurrent inoperable ameloblastoma was reported by Liu et al. Compared to conventional
radiotherapy, implant brachytherapy I-125 could continuously deliver high doses of radiation over a limited area, i.e.
up to 110 Gy is precise on the tumor and can avoid adjacent healthy tissue. The procedure was simple and the results
showed satisfactory local control with few side effects. 39
Prognosis
The prognosis of ameloblastoma depends on the patient's age, tumor’s size and location, tumor’s extensiveness, and
its histological type. Recurrence rate is determined by the adequacy of the surgical margin and involvement of the
surrounding vital structures. Maxillary ameloblastoma is more aggressive in terms of tumor’s extensiveness and high
recurrence rates. A theory states it may be due to the relatively thin layer of maxillary bone cortex that facilitates
spread of the tumor to the surrounding area. In addition, recurrence and reoperation can lead to increased morbidity
and risk of surgical complications.14

Metastatic ameloblastoma subtype shows mean disease-free survival of 13 years, with 2 years mean life expectancy
after metastasis.14

Young patients (less than 45 years of age) are reported to have better overall-survival compared to older patients and
there is no difference in progression-free survival. This matter reflects that there are still better salvage procedures for
young patients.6
Patients with ameloblastic carcinoma can experience local recurrence after definitive therapy in about 6 months to 11
years. Distant metastases usually appear no later than 4 months or even no later than 12 years postoperatively.

Therefore, periodic clinical and radiological (at least with a CT scan) follow-up every 6 months should be done. Long-
term prognosis depends on local recurrence and distant metastases. Surgery with wide surgical margin and definitive
or adjuvant radiotherapy can provide long-term disease control in certain cases. 6

Discussion
Ameloblastoma and ameloblastic carcinoma are fairly rare and locally aggressive diseases, with high recurrence rate
and potency of distant metastasis. Surgical resection with quite widespread negative surgical margin is the modality of
choice and adjuvant radiotherapy can be considered in postoperative cases with poor prognostic factors, as well as
inoperable and palliative cases. The main success factors associated with treatment is early diagnosis, both clinical and
radiological, as well as histopathological examination that becomes the diagnostic gold standard to achieve the correct
definitive diagnosis, since the tumor has various histopathological subtypes with different biological characteristics
that affect the prognosis.

Technological developments have driven advances in treatment modalities of radiotherapy. Given that radical surgery
is often not feasibly performed, radiotherapy, either by conventional techniques or IMRT, protons, or even carbon ion
radiation, still has a role to play in the management of these tumors. Radiotherapy shows particularly promising
results in the management of head - neck cancer, in which high doses can be given limited to the tumor with
avoidance of healthy tissue around it.

Meanwhile in the biomolecular field, knowledge of signaling pathways associated with the pathogenesis of
ameloblastoma has led to the development of targeted therapies for the management of these cases. Since SMO and
BRAF gene mutations are identified in ameloblastoma, administration of targeted therapy as a single agent is judged
to provide good enough results. However, data reporting the side effects still requires further study.

Appendix

Table 1. Odontogenic tumor and cysts classification (WHO 2017). 10

Malignant odontogenic tumor
Ameloblastic carcinoma
Primary intraosseous carcinoma, NOS
Sclerosing odontogenic carcinoma
Clear cell odontogenic carcinoma
Ghost Cell Odontogenic Carcinoma (GCOC)
Odontogenic carcinoma
Odontogenic sarcoma
Benign odontogenic tumor
Epithelial origin
Conventional ameloblastoma
 Unicystic type ameloblastoma
 Extraosseous / peripheral type ameloblastoma
 Metastatic (malignant) ameloblastoma
Squamous odontogenic tumor
Epithelial calcifying odontogenic tumor
Adenomatoid odontogenic tumor
Epithelial - Mesenchymal origin (mixed)
Ameloblastic fibroma
Primordial odontogenic tumor
Odontoma
 Compound type
 Complex type
Dentinogenic ghost cell tumor
Mesenchymal origin
Odontogenic fibroma
Myxofibroma / odontogenic myxoma
Cementoblastoma
Cemento-ossifying fibroma
 Odontogenic cyst
Developmental origin
Dentigerous cyst
Odontogenic keratocytes
Lateral botryoid and periodontal odontogenic cysts
Gingival cyst
Gland odontogenic cyst
Calcifying odontogenic cyst
Orthokeratin odontogenic cyst
Inflammatory origin
Radicular cyst
Collateral inflammatory cyst

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