Int. J. Oral Maxillofac. Surg.

2006; 35: 681–690

doi:10.1016/j.ijom.2006.02.016, available online at http://www.sciencedirect.com

Invited Review Paper

Oral Pathology

Recurrence related to treatment S. L. Lau, N. Samman

Oral and Maxillofacial Surgery, The University
of Hong Kong, Hong Kong, China

modalities of unicystic
ameloblastoma: a systematic
review
S. L. Lau, N. Samman: Recurrence related to treatment modalities of unicystic
ameloblastoma: a systematic review. Int. J. Oral Maxillofac. Surg. 2006; 35: 681–
690. # 2006 International Association of Oral and Maxillofacial Surgeons. Published
by Elsevier Ltd. All rights reserved.

Abstract. This systematic review aims to identify all studies pertinent to the clinical
question, ‘which treatment for unicystic ameloblastoma results in the lowest
recurrence rate?’ A structured systematic search of the literature, with predefined
inclusion and exclusion criteria, using computer and manual searches as well as
personal communication, was performed. Evaluations and critical appraisal were
done separately in 3 rounds. All searches were performed by 2 independent judges
and any disagreement was settled by discussion with a third party. Four treatment
modalities for unicystic ameloblastomas were identified. The recurrence rates were
3.6% for resection, 30.5% for enucleation alone, 16% for enucleation followed by
application of Carnoy’s solution and 18% for marsupialization with/without other
treatment in a second phase. It was concluded that there is only weak evidence
showing that jaw resection resulted in the lowest recurrence rate, followed by Key words: systematic review; ameloblastoma;
enucleation with application of Carnoy’s solution. Enucleation alone resulted in the unicystic; recurrence; treatment.
highest recurrence rate and treatment by marsupialization cannot be sufficiently
evaluated since most cases were followed by a second stage surgery of some kind. Accepted for publication 6 February 2006

Unicystic ameloblastoma was first
described by ROBINSON & MARTINEZ66 in
1977 as a special type of ameloblastoma.
According to the WHO 1992 definition,
ameloblastoma is a benign but locally inva-
sive polymorphic neoplasm consisting of
proliferating odontogenic epithelium,
which usually has a follicular or plexiform
pattern, lying in a fibrous stroma. This is
also true for unicystic ameloblastomas, but
its relatively younger age at presentation,
typically unilocular radiographic appear-
ance, macroscopically cystic nature and,
most important, its relatively better
response to conservative treatment, make
it a distinguishable entity.
Unicystic ameloblastoma usually app-
ears very similar to a non-neoplastic odon-
togenic cyst2,33 and is frequently clinically
misdiagnosed as dentigerous cyst and
odontogenic keratocyst, hence histological
confirmation is mandatory. VICKERS &
GORLIN in 197087 described 3 distinct his-
topathological features for unicystic ame-
loblastoma and these were slightly
modified by LEIDER et al.39 in 1985. ACKER-
3
MAN et al. in 1988 reported a series of 57
unicystic ameloblastomas and studied their
histological features in detail. They mod-
ified the diagnostic criteria defined by
ROBINSON & MARTINEZ66 and reclassified
the unicystic ameloblastoma into 3 sub-
types with prognostic and therapeutic

0901-5027/080681 + 10 $30.00/0 # 2006 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
682 Lau and Samman
significance. Type 1 – A unilocular cystic
lesion lined by epithelium which in areas
shows the criteria defined by VICKERS &
GORLIN. Type 2 – A nodule arising from the
cyst lining, projecting into the lumen of the
cyst, and comprising odontogenic epithe-
lium with a plexiform pattern which closely
resembles that seen in the plexiform ame-
loblastoma. Type 3 – The presence in the
connective tissue wall of the cyst, of inva-
sive islands of ameloblastomatous epithe-
lium which might (type 3b) or might not
(type 3a) be connected to the cyst lining.
Various treatment modalities for uni-
cystic ameloblastoma have been used,
such as segmental or marginal resection
as normally used for conventional amelo-
blastoma, however, more conservative
treatments have frequently been reported.
Enucleation28,39,66,78 and curettage28 are
mostly chosen. Some clinicians used mar-
supialization31,48,49,72 to reduce the size of
the lesion, followed by second stage sur-
gery. These treatments can be followed by
adjunctive therapy, including cryother-
apy22,32,43,58,71, thermal32 or chemical
cauterization38,82 and even radiother-
apy8,9,23,27,64,76 and chemotherapy86.
The reported recurrence rate after treat-
ment of unicystic ameloblastoma ranges
from 10 to 25%3,28,29,39,66,78. There is no
adequate evidence to prove which treat-
ment modality is the most effective and
the reasons for the practical variability and
controversy are many. First, many articles
did not describe the treatment in detail and
used general terms such as conservative
and radical treatment. Second, most did
not mention unicystic ameloblastoma as a
separate entity, but pooled the data
together with conventional types. Third,
many studies did not have an adequate
follow-up period making the reported
recurrence rate questionable. Finally, most
of the published articles are small case
series or even single case reports. Due to
the relative rarity of this tumour, good
evidence is difficult to arrive at.
The objective of this study was to conduct
a systematic review of the literature so as to
minimize the bias arising from single stu-
dies as described in the Cochrane Handbook
Section 4.2.4.17, namely, selection bias,
performance bias, attribution bias and
detection bias. The clinical question was
‘which treatment for unicystic ameloblas-
toma results in the lowest recurrence rate?’
This systematic review aims to identify all
studies that are pertinent to the ‘question’, to
select appropriate studies with pre-defined
criteria and then critically appraise them
with pre-established standards, targeting to
yield the best evidence that specifically
complies with the ‘question’.
Patients and methods regarding treatment modalities of unicys-
tic ameloblastoma and its recurrence were
A computer database search was per-
selected. Together with the articles
formed, through the use of MEDLINE
selected in the first round, they were all
(PubMed and Ovid), Embase and
retrieved for evaluation.
Cochrane Library, for all years available.
The same 2 judges independently eval-
Search key words used were (Ameloblas-
uated the full text of each of the retrieved
toma*) and (unicystic or cystic or cyst)
articles for the following inclusion cri-
and (recur or recurrence or relapse).
teria: (1) articles must belong to one of
Search was in all fields, all languages
the 5 levels of evidence defined in Table 1,
and all dates available.
(2) articles must not be concerning only a
specific site of the jaw, (3) articles must
First round—search not be concerning only one specific sub-
Electronic search type of unicystic ameloblastoma, (4) arti-
cles must not include only a specific group
Abstracts were reviewed, and articles rele- of subjects, e.g., age, gender. Standardized
vant to treatment modalities of unicystic evaluation charts were used. If the article
ameloblastoma and its recurrence were met all 4 inclusion criteria, it was marked
selected. If there was inadequate informa- as accepted. The article was marked as not
tion in the abstract, or if the citation did not accepted if one of these inclusion criteria
have an abstract, the article was also could not be fulfilled.
included in this round. Full articles were The judges were blind to each other, and
obtained for all those included in the first a split decision was settled by discussion.
round. If a consensus decision could not be made
by discussion between the 2 judges, a third
Manual search party was consulted.
Two relevant journals concerning oral
Third round—critical appraisal
pathology, not included in the available
databases, were searched manually for Each of the publications included in this
relevant articles. These were the Interna- round was critically appraised for assess-
tional Journal of Oral Medical Science ment of validity. This was done again by
and Oral Medicine and Pathology. the 2 independent judges with reference to
the following standards:
Unpublished articles
Standard 1—adequately conducted study
E-mail was sent to 15 major maxillofacial
centres in different parts of the world to For systematic review (SR) and meta-ana-
obtain any relevant unpublished articles or lysis—a full description of an appropriate
dissertations. Full articles were obtained. and pre-defined systematic search method,
All searches were done by 2 indepen- well-defined inclusion criteria and well-
dent judges. Any discrepancies between documented critical appraisal of the valid-
the views of the 2 judges for this preli- ity of the articles are required. Well
minary search were settled by discussion. explained statistical methodology and
If agreement could not be reached, advice proof of homogeneity are also needed
was sought from a third party. for meta-analysis. For Randomized con-
trolled trials (RCT)—adequacy of rando-
mization should be shown, mention of
Second round—search and evaluation
appropriate concealment, blinding and
Further manual search was performed intention to treat are required.
from the reference list of all the articles For case series, there should be no less
included in the 1st round. Again, articles than 5 cases in each study.
Table 1. Levels of evidence
Level Evidence
1 Systematic review of randomized controlled trials
2 Meta-analysis of randomized controlled trials
3 Randomized controlled trial
4 a. Systematic review/meta-analysis of controlled clinical trial
b. Controlled clinical trial
5 a. Systematic review/meta-analysis of case series
b. Prospective case series
c. Retrospective case series

Standard 2—adequate description of
patient selection
To minimize the bias imposed, patient
selection should be consecutive and a
complete collection of cases should be
included, rather than selection of patients
by the author. By definition, all case
reports and articles which only concern
a particular histological type, or a parti-
cular age group or gender of patients, will
be excluded.
Standard 3—adequate diagnostic
evaluation
The diagnosis of ameloblastoma, both the
primary lesion and the recurrent lesion,
should be based on histopathological eva-
luation and must be adequately described.
Clinical and radiographic diagnosis will
not be accepted.
Standard 4—adequate description of
follow-up and dropouts with explanations
The follow-up period must be mentioned
clearly. Although recurrence can occur up
to 21 years after treatment62, more than
50% of recurrences are encountered
within the first 5 years after treatment63.
The study will be accepted only if it has at
least a mean or median follow-up of 5
years. Dropout rate should be specified
clearly and possible explanations are
expected.
Standard 5—adequate description of the
treatment
The main aim of this study is to identify
the difference, in terms of recurrence after
treatment, between various treatment
modalities. A detailed description of the
treatment method, therefore, should be
given, including therapeutic agent applied,
special instruments used, etc.
Standard 6—adequate documentation of
adverse outcome
Adverse outcome of any kind after treat-
ment should be documented adequately.
Time of onset and rate of occurrence
should also be mentioned. Authors are
also expected to report the recurrence
for each treatment modality.
Standard 7—adequate clinical and
demographic information
The population pool should be described
in sufficient detail to identify the clinical
groups from which the patients were cho-
Recurrence related to treatment modalities of unicystic ameloblastoma
sen, so as to know whether the study has a
homogenous pool of patients or not. Also
the study populations should be studied in
detail to see whether they are comparable
to clinical situations which are under eva-
luation.
The articles were appraised using stan-
dardized appraisal charts and ranked into 3
categories according to the Cochrane
reviewers’ handbook Section 6.7.117:
(A) Low risk of bias
- plausible bias unlikely to seriously
alter the results, if all the standards
are met.
(B) Moderate risk of bias
- plausible bias that raises some
doubt about the results, if one or
more standards were partly met.
(C) High risk of bias
- plausible bias that seriously weak-
ens confidence in the results, if one
or more standards were not met.
Only articles with a low risk of bias were
included in the final review. Again, judges
were blind to each other, and split deci-
sions were settled by discussion. If a con-
sensus decision could not be made by
discussion between the 2 judges, a third
party was consulted.
Data were extracted from the finally
selected articles. Standardized data
extraction sheets were used. Sample
size, different treatment modalities,
follow-up period and recurrence rate were
all recorded. Also, general demographic
data such as age, sex, site of lesion were
noted.
Results
The electronic computer search yielded a
total of 232 potentially relevant articles
using the previously mentioned predefined
keywords. MEDLINE yielded 116 hits
from PubMed, and a further 87 hits from
Ovid. Embase yielded 29 more articles
while in the Cochrane database, there
was none. None of them were found to
be a systematic review, meta-analysis
or randomized controlled trial. After
reading through the abstracts, 41 articles,
related to the treatment of unicystic
ameloblastoma and its recurrence rate,
were selected1,5,7,10,13–15,18,20,21,29,30,33–
36,38–40,42,41,48,51,50,53,56,57,63,65–69,73,78,82–
85,89,90
. dropout rate was 8.3% in total.
Of the 15 major maxillofacial centres
contacted, 5 replied indicating no such
data were available. The remaining 10
centres did not respond and were assumed
to have no relevant data. Manual search of
the International Journal of Oral Medical
683
Science and Oral Medicine and Pathol-
ogy yielded no relevant data. The
electronic search, the search for unpub-
lished articles through e-mail, and the
manual search, therefore, all together
yielded 41 relevant articles and all were
entered into the second round search and
evaluation.
Manual search of the reference lists of
these 41 selected articles yielded a further
20 relevant citations4,6,11,12,16,24,45–
47,52,54,60,59,61,74,75,77,79–81
. Together with
the 41 articles form the 1st round, a total of
61 articles was entered for evaluation.
With reference to the predefined inclusion
standards, 40 articles did not fulfil one or
more inclusion criteria and were thus
excluded. The remaining 21 articles were
entered into the final round of critical
appraisal. They included articles in Eng-
lish, Chinese, German, Japanese and Thai.
Publication date ranged from 1967 to
2004.
The 21 articles were read in detail
and critically appraised with reference
to the 7 standards stated earlier. Twelve
articles were excluded due to possible
high risk of bias, 2 were excluded due
to possible moderate risk of bias and 1 was
excluded because it was found to be a
duplicate publication using the same
set of patient data elsewhere. This infor-
mation is described in detail in Table 2.
A total of 6 articles was included in
the final review (Table 3). Through this
explicit critical selection process, the
selected articles were the best available
valid data for analysis. Details of the
selection and evaluation process are pre-
sented in Fig. 1.
All the finally selected articles were
retrospective reviews. The total number
of patients with a treated unicystic amelo-
blastoma was 132. Ages ranged from 13 to
79 years, with a mean of 25.9 years. Male
to female ratio was 1.1:1. Ninety-six per
cent of lesions were located in the mand-
ible.
Data were retrieved and, if possible,
individual subjects who were not reported
to have a recurrence, but had a follow-up
period less than 5 years, were excluded.
Patients who were lost to follow-up were
also excluded from data analysis. In this
manner, 100 patients’ data were retrieved.
The mean/median follow-up was at least 5
years, ranging from 5 to 25 years. The
All treatment of unicystic ameloblas-
toma was surgical and was described in
sufficient detail to allow it to be repeated
by other clinicians. The treatment modal-
ities were broadly classified into 4 cate-
gories (Fig. 2):
684 Lau and Samman

Table 2. Excluded articles in the third round.

Potential risk
Year Author Title Reason of exclusion of bias Ref
11
1967 BECKER & PERTL Zur therapie des ameloblastoma 1. Did not differentiate between High
unicystic and other ameloblastoma
histologically
2. Inadequate follow-up period
80
1978 SIRICHITRA et al. Diagnosis and treatment 1. Inadequate follow-up period High
of ameloblastoma s in
school of dentistry,
Chulalongkorn University
4
1980 ADEKEYE Ameloblastoma of the jaws: 1. Did not differentiate between High
A survey of 109 Nigerian patients unicystic and other ameloblastoma
histologically
2. Inadequate follow-up period
77
1985 SHIMOSATO et al. Clinical observation of 1. Inadequate description of High
20 cases of ameloblastoma patient selection
2. Did not differentiate unicystic
ameloblastoma and other
ameloblastoma histologically
3. No follow-up period mentioned
89
1985 WANG Unicystic ameloblastoma: 1. Inadequate description of Moderate
A clinicopathological appraisal follow-up period (partly)
21
1988 EL-ABDIN & Unicystic ameloblastoma 1. No description of patient selection High
RUPRECHT in the Sudan
2. Inadequate follow-up period
82
1988 STOELINGA & The incidence, multiple 1. Inadequate follow-up period High
BRONKHORST presentation and recurrence
of aggressive cysts of the jaw
79
1993 SIAR Ameloblastoma in 1. No description of follow-up period High
Malaysia—A 25-year review
2. Inadequate description of treatment
68
1994 ROOS et al. Clinico-pathological study 1. No description of follow-up period High
of 30 unicystic ameloblastomas
2. Inadequate description of treatment
16
1996 CHIDZONGA et al. Ameloblastoma—The Zimbabwean 1. No description of follow-up period High
experience over 10 years
2. Inadequate description of treatment
42
2000 LI et al. Unicystic ameloblastoma—A 1. Inadequate description of treatment High
clinicopathological study of
33 Chinese patients
2. Inadequate description of
follow-up period (partly)
20
2001 D’AGOSTINO et al. Retrospective evaluation on 1. Inadequate description of treatment High
the surgical treatment of jawbones
ameloblastic lesion
69
2001 ROSENSTEIN et al. Cystic ameloblastoma—Behaviour 1. Inadequate follow-up period High
and treatment of 21 cases
41
2002 LI et al. Clinicopathological features 1. Double published N/A
of unicystic ameloblastoma with
special reference to its recurrence
34
2003 JUNQUERA et al. Ameloblastoma revisited 1. Inadequate description of Moderate
follow-up period

1. Resection: refers to either segmental
resections (surgically removing a sec-
tion of the mandible or the maxilla
without maintaining continuity) or
marginal resection, (surgically remov-
ing the tumour with a rim of unin-
volved bone and at the same time
maintaining the continuity of the
mandible or the maxilla). The choice
will usually depend on the site and size
of the lesion. In this series, there was a
total of 28 patients treated with resec-
tion, 13 of them were described as
having at least 1 cm of healthy bone
included in the resection, and 5 were
described as marginal resection. Of
these 28 patients, the mean follow-up
was 5.3 years with one recurrence
 Recurrence related to treatment modalities of unicystic ameloblastoma 685

Table 3. Included articles for final review

Number of cases
Mean follow-up
Year Author Title Excludeda Included Treatment (years) Recurrence Ref
66
1977 ROBINSON & Unicystic 9 11 Enucleation 9.2 3
MARTINEZ ameloblastoma—A
prognostically
distinct entity
39
1985 LEIDER et al. Cystic 22 11 Enucleation 6 4
ameloblastoma—A
clinicopathologic
analysis
50
1997 OLAITAN & Unicystic 0 11 Enucleation 8.3 (median) 2
ADEKEYE ameloblastoma
of the mandible: A
long-term follow-up
5 Marginal resection 8.3 (median) 1
5 Segmental resection 8.3 (median) 0
48
2002 NAKAMURA Comparison of 0 13 Resection (1 cm margin) >5 0
et al. long-term results
between different
approaches to
ameloblastoma
3 Marsupialization alone >5 0
8 Marsupialization with >5 2
enucleation and
bone curettage
38
2004 LEE et al. Unicystic 0 5 Resection 6.2 0
ameloblastoma—Use
of Carnoy’s solution
after enucleation
2 Enucleation 6.2 2
20 Enucleation with 6.2 2
application of
Carnoy’s solution
(extraction of closely
located teeth)
2 Enucleation with 6.2 2
application of Carnoy’s
solution (without
extraction of closely
located teeth)
15
2004 CHAPELLE Rational approach 1 1 Enucleation 15 0
et al. to diagnosis and
treatment of
ameloblastomas
and odontogenic
keratocysts
2 Enucleation with 13.5 0
application of
Carnoy’s solution
1 Enucleation after 10 0
application of
Carnoy’s solution
Total 100 6.57 18 (18%)
(median
excluded)
a
Cases excluded due to loss of follow-up or cases did not have a recurrence but inadequate follow-up period.

(3.6%) from the marginal resection
group.
2. Enucleation: refers to surgically shel-
ling the lesion out of the bone. The aim
is to remove the whole cyst/tumour
without leaving any visible remnants
behind. If microscopic remnants were
expected to have been left behind, enu-
cleation could be coupled with other
treatment modalities such as applica-
tion of chemical fixatives, electrocau-
tery, cryotherapy or curettage. In this
series, enucleation with or without
application of Carnoy’s solution was
encountered.
Enucleation only—There were 36
patients treated by enucleation alone,
with a mean follow-up period of 7.8
686 Lau and Samman
Fig. 1. Systematic article selection.
years, 11 of whom had a recurrence
(30.5%).
3. Enucleation with application of Car-
noy’s solution: Twenty-five patients
were treated with enucleation followed
by application of Carnoy’s solution
with a mean follow-up period of 6.9
years. In one paper, the stated duration
Fig. 2. Recurrence rate related to different treatment modalities.
of Carnoy’s solution application was
3 min and this accounted for 22 of
these patients38. The other authors
did not mention the duration of Car-
noy’s solution application for the
remaining 3 patients15. It was also
mentioned that 2 of the patients did
not have the teeth close to the tumour
removed, and one patient was treated
with application of Carnoy’s solution
before enucleation was done. A total of
4 patients had a recurrence (16%).
4. Marsupialization (+ other modal-
ities): This is also considered as exter-
iorization or decompression of the cyst,
this refers to surgically removing the
anterior bony wall of the lesion, and
suturing the incised edge of the cyst/
tumour to the adjacent mucosa or skin.
The authors explained that the bony
wall fenestration was made as wide
as possible, and after marsupialization,
a prefabricated acrylic obturator was
used to keep the window open. Patients
were reviewed at 3-month intervals
until they could withstand less aggres-
sive treatment such as enucleation or
curettage. If the marsupialization was
effective in reducing the size of the
lesion, it was followed by enucleation
and curettage. If this was not the case, it
was followed by resection. A total of 11
patients was treated by marsupializa-
tion. All patients were reported to show
a reduction in the size of lesion but to
different degrees. Three lesions totally
disappeared clinically after a mean
follow-up period of 5 years. Eight
patients were treated by enucleation
and curettage after marsupialization
and 2 of these had a recurrence. These
patients also had a mean follow-up
period of 5 years.
Discussion
Systematic reviews are defined as the best
level of evidence37,55,70 and frequently
emphasized in evidence-based practice,
because they minimize bias and error cre-
ated in single studies. A well conducted
systematic review can summarize all the
available and valid data to aid clinical deci-
sion, and can help researchers to objectively
define the boundaries of what is known and
what is not known. In this review, an effort
was made to include all possible articles
related to the study question.
Although 232 hits were recorded in the
1st round, only 6 articles were selected
into the final review. This is similar to
most systematic reviews in that often 5–10
articles will be entered into the final
review for data analysis. Unfortunately,
of these 232 hits, none were among the
first 4 levels of evidence, namely, sys-
tematic review of RCTs, meta-analysis
of RCTs, single RCT and non-randomized
controlled clinical trials (Table 1). Rather,
only retrospective studies were found.
This reflects the inadequacy of research

in this field, where large scale double blind
RCTs should be carried out, if possible, to
provide good and valid evidence to which
the clinician can refer. Although it is well
known that RCTs are difficult to perform
in the field of surgery, we believe that at
least a large-scale multicentre prospective
trial with long-term follow-up should be
feasible.
The final round of critical appraisal
included 21 articles, with only 6 selected
for the final review. Of the 15 articles
excluded, 12 had inadequate follow-up
period, or inadequate description of the
follow-up period, which made this the
most common cause of non-validity in
the literature. As mentioned by REICHART
et al.63 in a review of 3677 ameloblasto-
mas, more than 50% of recurrences
occur in the first 5 years but possibly as
late as 33 years; we, therefore, decided
that any study with less than a mean or
median follow-up period of 5 years should
be excluded. The reported follow-up per-
iod in the case series published by JUN-
34
QUERA et al. was noted to be 1–23 years;
despite a good attempt to contact the
authors for a mean follow-up period, no
reply was received, hence this article was
excluded. The second most common
cause of non-validity was inadequate
description of treatment, followed by
pooling of data on unicystic ameloblas-
toma and conventional ameloblastoma.
Surprisingly, one article was found to
be a duplicate publication and was
excluded (Table 2).
The remaining 6 articles, which were
entered into the final review, are thought to
be of good quality. Although all are retro-
spective case series, they are the best
available (Table 3). In these studies, there
were a total of 132 cases of unicystic
ameloblastomas reported. Whenever pos-
sible, cases where the patient was lost to
follow-up, or when the individual follow-
up period was less than 5 years without a
recurrence, were deleted. This left a total
of 100 patients whose data were retrieva-
ble. The general demographic data
showed almost no sex predilections, and
a mean age of 25.9 years. The unicystic
ameloblastomas were exclusively located
in the mandible and the overall mean
follow-up period was calculated to be
6.57 years. In the article published by
OLAITAN & ADEKEYE50 and LEE et al.38,
the median was used to report the follow-
up time. Authors were contacted to
retrieve a mean follow-up period for easy
calculation; OLAITAN & ADEKEYE. could
not be reached and the case series was
omitted during the calculation of the over-
all mean of the follow-up time.
Recurrence related to treatment modalities of unicystic ameloblastoma
Treatment modalities were grouped into
4 categories. Enucleation alone yielded
the highest recurrence rate among all treat-
ments (30.5%). The explanation is 2-fold.
First, the cystic lining of the tumour is
inadequately removed. Sometimes, espe-
cially in posterior maxillary ameloblasto-
mas, the tumour is not perfectly rounded
or oval in shape so the enucleation may not
be as simple as expected, and remnants
can be left behind in complex anatomical
structures without being noticed. Second,
the ameloblastic tumour cells can invade
the cancellous bone to a certain extent.
MARX et al.44 demonstrated that amelo-
blastoma can extend from 2.3 to 8 mm
beyond the radiographic margin of the
tumour, thus, by enucleation alone, the
ameloblastic cells will be left behind
despite the tumour being enucleated
whole. This is also likely to occur in the
so-called mural subtype of unicystic ame-
loblastoma, later defined by ACKERMAN
et al.3 as the type 3 unicystic ameloblas-
toma.
Resection for unicystic ameloblastoma
results in the lowest recurrence rate
(3.6%). It is clear that, if an adequate bone
margin is removed, the chance of recur-
rence can be expected to be low. However,
a balance in judgment is required when
selecting this treatment option so that
maximum success does not lead to over-
treatment. Despite the high success rate of
resection for unicystic ameloblastoma,
more conservative treatment in order to
optimize quality of life is generally
favoured. Better diagnostic techniques
and close follow-up enable prompt treat-
ment once a recurrence is detected.
Enucleation followed by the application
of Carnoy’s solution has resulted in a
recurrence rate of 16%, which was the
best, except for resection. There are only
a few publications reporting unicystic
ameloblastoma treated by this method.
In the case series reported by LEE
et al.38, 2 of the patients who had a recur-
rence were treated by enucleation with
application of Carnoy’s solution but with-
out extraction of the closely related teeth.
In an attempt to preserve the tooth without
damage, tumour remnants may be left
around the tooth apex or root and this
may have led to the recurrence. Otherwise
the recurrence rate with this method may
ultimately prove to be even lower than
reported.
Carnoy’s solution, a powerful tissue
fixative that can penetrate bone to
1.54 mm88, was first described by CULTER
& ZOLLINGER19 in 1933 as a treatment for
cystic lesions. Carnoy’s solution is, there-
fore, also likely to penetrate cancellous
687
spaces and thus devitalize and fix the
remaining tumour cells. The success of
the application of this agent after enuclea-
tion was thought to be due to both its
penetration and fixation action. The usual
practice is to apply Carnoy’s solution with
cotton applicators or ribbon gauze for 3–
5 min, rinse the bony cavity and pack the
wound open for healing by secondary
intention. Primary closure is likely to pre-
cipitate infection of necrotic debris. How-
ever, FRERICH et al.25 suggested the
application of Carnoy’s solution should
not exceed 3 min. They showed that the
critical time to nerve impairment of the
rabbit inferior alveolar nerve was 3 min,
and that Carnoy’s solution should not be
applied directly over the nerve. Though
there remains a need for human studies,
the use of Carnoy’s solution to reduce
recurrence rate should be balanced against
the risk of nerve morbidity.
In one case reported in the series pub-
lished by CHAPELLE et al.15, enucleation of
the tumour after the application of Car-
noy’s solution was described. This
method, originally described by VOORS-
88
MIT for treating odontogenic keratocysts,
had until then never been reported for
unicystic ameloblastoma, hence the actual
effect of the Carnoy’s solution application
before tumour enucleation remains
unknown. The same authors suggested
excisional biopsy for all unilocular
lesions15 by enucleation. If the pathologi-
cal result showed a type 1 or type 2
unicystic ameloblastoma, they proposed
follow-up and a wait-and-see policy, with
further treatment to be given only if and
when a recurrence is noted. Nevertheless,
for a pathological diagnosis of Ackerman
type 3 unicystic ameloblastoma, these
authors recommend resection in the form
of partial maxillectomy, marginal resec-
tion or segmental resection of the mand-
ible immediately upon receiving the
pathological diagnosis. The rationale for
their treatment without an incisional
biopsy is that a small tissue biopsy may
not reflect the specific Ackerman-types of
unicystic ameloblastoma because the pat-
tern of mural invasion may not necessarily
be shown all around the cyst, thus the
chance of under-diagnosis is high. The
limited data available, however, support
application of Carnoy’s solution following
enucleation as yielding a limited recur-
rence rate even for Ackerman type 3 uni-
cystic ameloblastomas38.
Marsupialization together with other
treatments resulted in an 18% recurrence
rate. This rate cannot be fully attributed to
marsupialization on its own, as most pro-
cedures were followed by second stage
688 Lau and Samman
surgery. The aim of marsupialization was
to reduce the size of the unicystic amelo-
blastoma so that less extensive surgery is
required. Shrinkage of the lesion was
noted in more than half of the cases
included. This treatment modality is not
popular but most benefit is expected in
severely ill patients or those with a huge
lesion. Interestingly, 3 reported cases had
complete resolution after marsupialization
alone. The reason remains unknown
because, by definition, a tumour should
not regress by exteriorization. However,
details were not recorded in these 3 cases,
hence this concept remains in need of
justification through a larger study with
better-defined criteria and long-term fol-
low-up.
Although the data show that the lowest
recurrence rate was the result of resection,
it is widely believed that resection should
not be mandatory except for lesions
located in a difficult site, such as the
posterior maxillary region, where retreat-
ment will be difficult and additional sur-
gical morbidity would be imposed. A
more conservative approach is recom-
mended, entailing enucleation with appli-
cation of Carnoy’s solution and the
extraction of closely related adjacent teeth
after confirmation of the diagnosis of uni-
cystic ameloblastoma by incisional
biopsy. This approach results in low sur-
gical morbidity and a low recurrence rate.
It is worth emphasizing that the follow-up
period should be maintained for at least 5
years, and that routine radiography should
be performed at each annual visit. A large
scale randomized controlled trial, or at
least a well planned prospective study,
on enucleation and application of Car-
noy’s solution in the treatment of unicystic
ameloblastoma is recommended. The
duration of application of Carnoy’s solu-
tion should be defined by balancing the
recurrence rate with inferior alveolar
nerve morbidity, and the effect of applica-
tion of Carnoy’s solution before or after
enucleation should be studied. Cryother-
apy in conjunction with enucleation was
not included in this review since all arti-
cles were single case reports or small case
series, however the initial results are pro-
mising even in cases with long-term fol-
low-up. A more precise comparison of
cryotherapy with liquid nitrogen and
application of Carnoy’s solution in con-
junction with enucleation, is recom-
mended.
In summary, there is weak evidence
showing that resection resulted in the low-
est recurrence rate (3.6%), followed by
enucleation with application of Carnoy’s
solution (16%). Enucleation alone resulted
in the highest recurrence rate (30.5%), and
treatment by marsupialization could not
be sufficiently evaluated since most cases
were followed by a second stage surgery
of some kind. Systematic reviews can aid,
but can never replace, good and sound
clinical reasoning. Careful thought should
be applied and tailored to individual
patients and situations based not only on
good evidence, but also on experience,
availability of time and resources and
compliance.
Acknowledgement. The authors would like
to thank Dr Century Tsang for help with
the literature search.
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Address:
Nabil Samman,
Oral and Maxillofacial Surgery
Faculty of Dentistry
The University of Hong Kong
Prince Philip Dental Hospital
34 Hospital Road
Hong Kong
China
Tel: +852 28590363
Fax: +852 28575570
E-mail: nsamman@hku.hk