J HK Coll Radiol 2005;8:157-161 M Philip, CG Morris, JW Werning, WM Mendenhall

ORIGINAL ARTICLE

Radiotherapy in the Treatment of Ameloblastoma and

Ameloblastic Carcinoma
M Philip,1 CG Morris,1 JW Werning,2 WM Mendenhall1
Departments of 1Radiation Oncology and 2Otolaryngology, University of Florida College of Medicine,
Gainesville, Florida, USA

ABSTRACT
Objective: To determine the efficacy of radiotherapy in the treatment of ameloblastoma and ameloblastic
carcinoma.
Patients and Methods: Two patients with ameloblastoma and 3 patients with ameloblastic carcinoma were treated
with radiotherapy alone (1 patient) or surgery and postoperative radiotherapy (4 patients) at the University of
Florida between 1973 and 2004. Follow-up ranged from 10 months to 3.3 years; no patient was lost to follow-up.
Results: Local control was achieved in all 5 patients. No patient developed regional or distant metastasis. One
patient died of intercurrent disease at 2.1 years; 4 patients were alive and disease-free. No significant treatment-
related complications were observed.
Conclusion: Adjuvant postoperative radiotherapy improves the likelihood of local control after surgery when
margins are close or microscopically positive. Limited data suggest that radiotherapy alone may occasionally
control patients with unresectable tumours.

Key Words: Ameloblastoma, Head and neck neoplasms, Radiotherapy, Treatment outcome

INTRODUCTION or bridges, periodontal disease, ulceration, paresthesia,

Ameloblastomas are benign, locally invasive tumours
constituting 1% of all tumours and cysts arising in the
mandible and maxilla. They account for 11% of all
odontogenic tumours. Approximately 80% arise in the
mandible (most commonly in the molar-ramus region)
and the remainder occur in the maxilla. 1-4 Amelo-
blastomas arising in soft tissues are rare.5
Most patients are diagnosed in the third to fifth decade
of life.3,6,7 However, the tumour grows slowly and prob-
ably starts to develop between early childhood and
young adulthood.2,8 Gender distribution varies but is
probably about 1:1. Most authors report an equal racial
distribution.2-4 The most common presentation is a pain-
less swelling of the jaw. Additional symptoms include
malocclusion, pain, tooth mobility, ill-fitting dentures
Correspondence: Dr. William M. Mendenhall, Department of
Radiation Oncology, University of Florida Health Science Center,
PO Box 100385, Gainesville, FL 32610-0385, USA.
Tel: (352) 265-0287; Fax: (352) 265-0759;
E-mail: mendewil@shands.ufl.edu
Submitted: 8 April 2005; Accepted: 25 January 2006.
and/or anesthesia of the affected area.3,4,6,7
Histologically, ameloblastomas arise from cell remnants
of the embryonic tooth, particularly the dental lamina
or inner enamel epithelium. They are composed of a
central area of stellate epithelial cells known as the
stellate reticulum and are surrounded by a periphery of
vacuolated columnar epithelial cells. The peripheral cells
are regarded as the reserve cells. The stellate reticulum
may undergo squamous metaplasia.9,10
Ameloblastomas exhibit various histological patterns;
the 2 most common are follicular and plexiform. Others
include acanthomatous, granular, basaloid, and desmo-
plastic. These patterns may exist singly or in combin-
ation. The tumours are also subdivided into 4 variants
based on overall histologic architecture including
solid, multicystic, multicystic plus solid, and unicystic
types. Apart from the unicystic variant, which has
a lower recurrence rate, the histological pattern does
not influence clinical behaviour.9-11 Gross morphology
and location are more important in predicting tumour
aggressiveness.12,13

© 2005
J HK Hong
Coll Kong
Radiol College of Radiologists
2005;8:157-161 157
RT for control of ameloblastoma

Two rare forms of malignancy are associated with
ameloblastoma: malignant ameloblastoma and amelo-
blastic carcinoma. The cardinal feature of malignant
ameloblastoma is metastatic spread. The histologic
appearance of the primary and metastatic lesions is
indistinguishable from benign ameloblastoma. In
contrast, the primary and metastatic lesions of an
ameloblastic carcinoma show histologically malig-
nant epithelial features similar to an epidermoid
carcinoma.14,15
Regional nodal metastases and/or hematogenous
dissemination may occur.15-18 Seventy five percent of
distant metastases arise in the lungs, while the remain-
ing lesions occur predominantly in the bones (i.e., skull,
vertebrae, ribs, and femur). The median survival after
development of distant metastases is 2 years.19
Surgery is the mainstay of treatment for ameloblastoma
and ameloblastic carcinomas. The optimal treatment for
ameloblastic carcinomas is resection with wide margins.
However, because ameloblastomas are benign, the
extent of the resection is controversial. Less aggressive
resections are often employed to avoid the potential
morbidity associated with wide excisions.20 Recurrence
rates of ameloblastomas are as high as 15% to 25%
after wide resection and 65% to 90% after less exten-
sive operations such as curettage.9,20-25 The initial sur-
gical intervention offers the best chance of cure and
reducing the risk of developing metastases.
Ameloblastomas have been reported to be radio-
resistant and, thus, radiotherapy (RT) has generally been
reserved for palliation of patients with unresectable
tumours.26 Most recently, RT has been employed with
some degree of success.27 Isolated case reports exist
describing the efficacy of chemotherapy and, in general,
it appears to be relatively ineffective.28
The aim of this report is to present our experience with
RT in the treatment of patients with ameloblastomas and
ameloblastic carcinomas, and to review the pertinent
literature.
PATIENTS AND METHODS
Five patients were treated with curative intent with RT
alone (1 patient) or following surgery (4 patients) at the
University of Florida between 1973 and 2004. A tissue
diagnosis was available in all patients. Four patients had
a tumour located in the maxilla and 1 patient had a man-
dibular lesion. Two patients had amelobastomas and
3 had ameloblastic carcinomas. Four patients were
treated for lesions that were recurrent after one or more
operations. No patient presented with regional node
involvement or distant metastasis.
Four patients underwent resection (Table 1). Margins
were close in 2 patients and microscopically positive in
2 patients. RT doses ranged from 63 to 72 Gy. Three
patients received once-daily RT, 1 patient received
twice-daily fractionation, and 1 patient was treated with
a combination of the 2 techniques. One elderly patient
was treated with RT alone for an advanced recurrent
tumour of the maxilla (Table 1). Follow-up ranged from
10 months to 3.3 years. No patients were lost to follow-
up. All living patients were contacted or seen within 1
month of data analysis. Local control was defined as no
evidence of disease at the primary site on subsequent
physical examinations and/or radiographic studies
until last follow-up or death. Death from intercurrent
disease was defined as death without evidence of re-
current tumour.

Table 1. Patient population.

Patient Age (years)/ Primary Histology Prior Surgery Resection Radiotherapy Outcome
gender site treatment margins
1 70/m Maxilla Ameloblastic Surgery x 1 Partial Close 66.4 Gy/46 fx/ NED 3.3 years
carcinoma maxillectomy QD/BID
2 70/m Mandible Ameloblastic None Segmental Close 66 Gy/33 fx/QD NED 2.1 years
carcinoma mandibulectomy (<0.5 mm)
3 56/m Maxilla Ameloblastic Surgery x 1 Total Microscopically 72 Gy/60 fx/BID NED 0.83 years
carcinoma maxillectomy positive
and resection
of orbital floor
4 82/m Maxilla Ameloblastoma Multiple None - 66 Gy/39 fx/QD DID 2.1 years
operations
5 61/m Maxilla Ameloblastoma Multiple Maxillectomy Microscopically 63 Gy/35 fx/ QD NED 2.1 years
operations positive
Abbreviations: m = male; fx = fractions; QD = once-daily fractionation; BID = twice-daily fractionation; NED = no evidence of disease; DID = dead of intercurrent
disease.

158 J HK Coll Radiol 2005;8:157-161


RESULTS
Local control after RT was observed in all 5 patient (100%).
No patient developed a regional or distant recurrence.
Four patients are alive and disease-free and 1 patient
died of intercurrent disease. No patient suffered a
severe treatment-related complication.
DISCUSSION
Surgery
Surgery is the optimal treatment for patients with amel-
oblastoma and ameloblastic carcinoma. The optimal
surgical approach remains controversial. Conservative
options include enucleation, curettage, cryotherapy,
electrocautery, marsupialization, or any combination of
the above. Wide resection involves segmental or rim
resection of the mandible or maxilla.20,24,25
Conservative resections have resulted in high local
recurrence rates. Sehdev et al reported local recurrences
in excess of 90% in a series of 92 patients with amelob-
lastoma treated with curettage alone.21 With a mean
follow-up of 3 years, Sampson and Pogrel reported a
100% local recurrence rate in 11 patients undergoing
curettage for ameloblastoma.20
Some authors have emphasized the importance
of distinguishing unicystic from the solid or multi-
cystic variant of ameloblastoma; the latter warrants
more aggressive surgical intervention. Muller and
Slootweg reported a series of 84 patients and ob-
served local recurrence rates of 75% versus 20% after
conservative resection of multicystic versus unicystic
ameloblastomas.22 Following wide resection for multi-
cystic tumours, the recurrence rate declined to 15%.
In addition, they noted that 95% of local recurrences
developed within 5 years after surgery.
Gardner and Pecak reported that conservative surgical
treatment should be considered only in the presence of
unicystic lesions when extraosseous spread has not
occurred.12 They concluded that unacceptably high re-
currence rates occur in the multicystic or solid variant,
which often exhibits invasion into the intertrabecular
spaces of the cancellous bone, making complete resec-
tion with conservative methods exceedingly difficult.
In addition, Gardner and Pecak concluded that amelo-
blastomas in the posterior part of the maxilla should be
treated more aggressively than similar lesions in the
mandible, due to the proximity of vital structures and
difficulty of treating subsequent recurrences.12
J HK Coll Radiol 2005;8:157-161
M Philip, CG Morris, JW Werning, WM Mendenhall
Due to the high risk of local recurrence, optimal resec-
tion requires a more than 1 cm margin of uninvolved
cancellous bone surrounding the primary tumour.29,30
However, local recurrence rates are as high as 15% to
25% after wide resection. Reportedly, salvage surgery
can control 80% of mandibular tumours but only 40%
of maxillary tumours.21,30 Therefore, patients at high risk
for developing recurrence after surgery should be con-
sidered for adjuvant therapy.
Radiotherapy
There are relatively few data pertaining to the efficacy
of RT. Robinson reported one of the first series, in which
18 patients were treated with RT alone; 13 patients
(72%) developed a local recurrence.1 RT consisted of
orthovoltage external beam RT, radium needles, or
radon seeds.1 Sehdev et al reported on 11 patients treated
at the Memorial Sloan Kettering Cancer Center with
RT between 1921 and 1951.21 Although the tumour
initially responded in some patients, all eventually ex-
perienced progression of persistent disease or a local
recurrence.
Recently published studies analyzing the efficacy of
megavoltage therapy in the management of ameloblas-
toma have questioned the proposition that these tumours
are inherently radioresistant. Gardner reported on
3 patients treated with megavoltage RT (40, 45 and
55 Gy, respectively); all 3 responded initially but later
recurred.31 Based on these results, Gardner concluded
that RT can produce regression of an ameloblastoma,
particularly the part which causes expansion of the
jaw or has invaded the adjacent soft tissues but that it
is not appropriate treatment for ameloblastomas and
should be reserved for unresectable tumours.31
Atkinson et al published a case series of 10 patients
treated at Princess Margaret Hospital between 1958 to
1982.27 Two patients underwent total excision and post-
operative RT and 1 patient underwent subtotal excision
and RT; all 3 remained alive and disease-free at 27
months, 30 months, and 5 years after treatment. Seven
patients were treated with RT alone; 1 patient had per-
sistent disease and required further treatment and the
remainder experienced slow regression of the tumour
which remained locally controlled in all 6 patients.
In a case report and review of the literature, Miyamoto
et al asserted that ameloblastoma is radiosensitive.32
They proposed guidelines for treatment planning as
follows: 1) RT portals should include the entire tumour
159
RT for control of ameloblastoma
volume with a 2 cm margin, 2) lymph nodes should not
be included unless clinical involvement is suspected,
and 3) doses of at least 45 to 50 Gy in 4 to 5 weeks using
1.8 Gy fractions are necessary to control the tumour.
All 5 of our patients treated with surgery and RT (4
patients) or RT alone (1 patient) have remained disease-
free after treatment.
Chemotherapy
Experience with chemotherapy is minimal in the
treatment of ameloblastoma and is largely limited
to isolated cases. Lanham described a case report of
ameloblastoma metastatic to the lungs and submandi-
bular nodes treated with doxorubicin, cisplatin, cyclo-
phosphamide, dacarbazine, and 5-fluorouracil; the
tumour failed to respond.28 Duffey et al reported a case
of ameloblastoma with dissemination to cervical lymph
nodes, liver, and lungs treated with multi-agent chemo-
therapy.33 The tumour did not respond to treatment.
In contrast, Grunwald et al described a case of amelo-
blastoma metastatic to the lungs and pleura, which
exhibited response to paclitaxel and carboplatin.34
CONCLUSIONS
Our experience indicates that the probability of control-
ling local recurrence of ameloblastoma and ameloblastic
carcinoma with surgery and adjuvant RT is high. All
of the 4 patients in our series treated with surgery and
RT remained locally controlled after treatment. There
are few data in the literature pertaining to the efficacy
of RT alone. It appears that RT alone probably controls
approximately half of those treated. Thus, patients who
have tumours that are amenable to gross total resection
should be treated surgically.
We currently employ adjuvant RT in patients with
ameloblastomas that have been resected with positive
margins and in whom salvage surgery would likely be
ineffective. RT alone for gross disease is employed only
by default if the disease is unresectable. Ameloblastic
carcinoma is treated in the same manner as other more
common oral cavity carcinomas with surgery and post-
operative RT depending on the pathologic findings.
Indications for RT include close or positive margins,
multiple positive nodes, extracapsular invasion, and
perineural invasion.
RT doses range from 60 to 70 Gy using once- or twice-
daily fractionation. In patients with ameloblastic carci-
noma, regional nodal irradiation should be considered.
160
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