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Intraosseous ameloblastoma
Harvey P. Kessler, DDS, MS
Division of Pathology, Department of Diagnostic Sciences, Baylor College of Dentistry, 3302 Gaston Avenue
Dallas, TX 75246, USA
The ameloblastoma is a true neoplasm of odonto-
genic epithelial origin. It is the second most common
odontogenic neoplasm, and only odontoma outnum- bers it in reported frequency of occurrence [1–3].
Excluding odontoma, the incidence of ameloblastoma
is at least equal to the incidence of all the other
odontogenic neoplasms combined [2]. Its incidence,
combined with its clinical behavior, makes amelo-
blastoma the most significant odontogenic neoplasm
of concern to oral and maxillofacial surgeons. As
seen with nearly every odontogenic neoplasm, the
ameloblastoma may occur centrally within bone or
peripherally, without an intraosseous component, in
the soft tissues overlying the alveolar ridge [3–5].
Intraosseous lesions outnumber peripheral lesions by
at least a 9:1 margin [1,4,5].
Demographic data
Ameloblastoma occurs over a broad age range;
cases have been reported in children younger than
10 years through elderly adults older than 90 [1].
The average age at diagnosis consistently is reported
in the age range of 33 to 39, and most cases cluster
between ages 20 and 60 years [1–3,6,7]. Only about 10% of cases are reported to arise in children, and
less than one third of those occur in children younger
than 10 years [8]. No significant sex predilection has
been reported [1–3,6,7]. There is conflicting evidence
on the incidence rates in different races. Although
some reports claim an increased incidence of amelo-
blastoma in black individuals [2,9], a large study
identifies Asians as the population with the greatest
number of affected patients [1]. Because sizeable
numbers of cases are reported in every racial group,
race does not seem to be a significant defining de-
mographic characteristic of the disease [3].
Origin
The origin of ameloblastoma is not known with
certainty, but in concert with concepts of neoplasia in
general, it is likely the result of alterations or muta-
tions in the genetic material of cells that embryologi-
cally are preprogrammed for tooth development.
Environmental factors and individual patient varia-
bles (eg, general health status, nutritional status) also
likely have a role in modulating the incidence of the
disease [1,3]. This theory is demonstrated by the
finding that the average age of occurrence of amelo-
blastoma in industrialized nations is 10 to 15 years
greater than that seen in developing countries [1].
Site of occurrence
Ameloblastoma occurs in all areas of the jaws, but
the mandible is the most commonly affected area
(more than 80% of all cases occurring there) [1–3,6].Within the mandible, the molar-angle-ramus area is
involved three times more commonly than are the
premolar and anterior regions combined [2,3]. Statis-
tics on the location of maxillary ameloblastomas are
more variable and more difficult to interpret. Some
studies report a low incidence in the anterior maxilla
[9–11], whereas other studies suggest that the inci-
dence in the anterior maxilla is roughly equivalent to
the incidence in the maxillary molar region [2,6,12].
Part of this problem stems from the involvement of
the maxillary sinus or nasal cavity by the ameloblas-
toma in a number of cases that originate in the
1042-3699/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.coms.2004.03.001
E-mail address: hkessler@tambcd.edu
Oral Maxillofacial Surg Clin N Am 16 (2004) 309–322
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maxilla [6]. Some studies label sinonasal areas as a
separate category when reviewing maxillary amelo-
blastomas, but most do not. Ameloblastomas also
have been reported to arise primarily in the sinonasal
regions without overt evidence of origin from the
tooth-bearing alveolar bone [11]. This lack of uni-formity in recording the site of maxillary involvement
hinders compilation and comparison of statistical data
from multiple studies. When comparing large studies,
it appears that maxillary tumors tend to occur in
slightly older patients than do mandibular lesions
[6,9]. The incidence of occurrence of ameloblastoma
in different sites within the jaws has been shown to
vary among racial groups [3]. Asians seem to have
fewer tumors involving the ramus than do whites or
blacks, whereas blacks have an increased frequency
of tumors in the anterior mandible compared with theother two groups [1,3].
Clinical presentation
Patients with ameloblastoma most commonly
present with chief complaints of swelling and facial
asymmetry [1–3,8,11,13]. Although the swelling is
typically asymptomatic, pain is an occasional pre-
senting sign [2,3,9]. A chief complaint of painless
swelling often heralds a lesion of long duration and
significant size [1,3]. The average reported size of ameloblastomas in the largest study to date was
4.3 cm [1]. Continued growth of the tumor and
enlargement of the involved area may eventuate in
ulceration of the mucosa overlying the lesion [1,9].
Small lesions tend to be discovered more often on
routine radiographic screening examinations or as a
result of local effects produced by the tumor [1,2].
Such local effects include tooth mobility, occlusal
alterations, and failure of eruption of teeth [3,9].
Radiographic presentation
Radiographically, the intraosseous ameloblastoma
classically is described in dental periapical and pano-
ramic films as a multilocular or ‘‘soap-bubble’’
radiolucency [2,14]. The increasingly routine use of
CT studies in evaluating the clinical extent of lesions
has resulted, however, in accumulating evidence that
truly multilocular ameloblastomas are not encoun-
tered often. When visualized in CT images, lesions
that appear multilocular on plane films usually show
scalloping resorption of the delimiting cortical platesrather than compartmentalized areas separated by true
bony septa [3]. The scalloping of the cortex produces
the illusion of a multilocular process on the plane
films. Other reported radiographic patterns seen in
dental radiographs are a smooth bordered unilocular
radiolucency, a unilocular lucency with a scalloped or
lobulated border, and, in the case of one specific
histologic subtype, a poorly delineated mixed lucent-opaque lesion that oft en is mistaken for a benign
fibro-osseous process [1,3,8,14–18]. Impacted teeth
associated with the radiographic lesion commonly are
encountered, occurring in 15% to 40% of all cases
[3,14]. More than half of unilocular-appearing lesions
of ameloblastoma are reported to be associated with
an impacted tooth, and the lesion typically is found
surrounding the crown of the impacted tooth in a
dentigerous cyst-type relationship [14]. The mandibu-
lar third molar is the most commonly involved tooth
[3,14]. Unilocular lesions associated with an im- pacted tooth also tend to be found in significantly
younger patients compared with patients with multi-
locular lesions [1]. A large proportion of the amelo-
blastomas reported in young children are found in
this clinical setting [8]. A mixed lucent-opaque ra-
diographic appearance in a lesion histopathologically
diagnosed as ameloblastoma signals the presence of
the desmoplastic type of ameloblastoma. This variant
first was described in 1984 by Eversole et al [17].
Only about 25% of desmoplastic ameloblastomas pro-
duce this mixed lucent-opaque pattern, however [16];
the remainder produce entirely radiolucent lesions.Unlike the other types of ameloblastoma, the desmo-
plastic variant regularly presents with an ill-defined
radiographic margin [1,15].
Histopathology
Six histopathologic subtypes of ameloblastoma
are recognized: follicular, acanthomatous, granular
cell, basal cell, desmoplastic, and plexiform [1–3,
9,16,19]. Most tumors show a predominance of one pattern, but few lesions are found to be composed
purely of one histopathologic subtype [2,3]. Mixtures
of the different patterns commonly are observed.
Lesions tend to be subclassified according to the pre-
dominant pattern that is present. The various subtypes
have been studied and analyzed extensively to deter-
mine if there is any clinical significance to warrant
histologic subclassification. Some minor correlation
has been noted between the location of the lesion in
the jaws and the histologic subtype [1]. The age of
the patient and the histologic subtype also show some
correlation [1]. Because neither of these correlationshave prognostic implications or affect treatment deci-
sions, histologic subclassification of ameloblastoma
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for many years was believed to be only an academic
exercise for oral and maxillofacial pathologists [2,10,
13,20]. The lit erat ure-based retrospective study by
Reichart et al [1] introduced a new concern: The
histologic subtype may have prognostic implications
for recurrence. According to their study, the follicular type of ameloblastoma had the highest rate of recur-
rence at 29.5%. In contradistinction, the acanthoma-
tous type of ameloblastoma showed only a 4.5%
recurrence rate. The plexiform subtype was interme-
diate between the two extremes and showed a 16.7%
recurrence rate. These differences were deemed to be
statistically significant [1]. Too few cases of the
granular cell and basal cell subtypes were available
for valid statistical analysis, but recurrences were
documented in both types. In Reichart et al’s study
[1], none of the desmoplastic cases recurred, but therewere not enough cases in this category for valid
statistical analysis. Other studies have verified that
desmoplastic ameloblastoma shows a tendency to
recur, and the rate of recurrence is reported within
the range of the other histologic subtypes of amelo-
blastoma [15,18]. Reichart et al’s study [1] also
contained a category for recurrence rates associated
with lesions that showed a mixture of histologic
patterns. The difference between this rate (14.3%)
and that for the follicular subtype was deemed
statistically significant. Additional studies of recur-
rent cases, with increased numbers of all the different histologic subtypes, are necessary to confirm or refute
these statistics.
Core histologic features
On microscopic examination, most histologic vari-
ants of ameloblastoma show a core group of distinc-
tive cytomorphologic and architectural characteristics
that facilitates their recognition and diagnosis. This
core group of distinctive characteristics includes(1) the nature of the background stroma of the tumor,
(2) growth pattern of the epithelium that makes up the
tumor, (3) staining pattern of the neoplastic cells,
(4) cellular morphology, and (5) nuclear orientation.
The follicular, acanthomatous, granular cell, basal cell,
and desmoplastic subtypes show considerable simi-
larity when these characteristics are compared among
the groups. Only the plexiform subtype shows sig-
nificant variations from this core group of character-
istics. Because the follicular subtype is the most
commonly encountered variant [1], some pathologists
believe that the acanthomatous, granular cell, basalcell, and desmoplastic variants are subsets of the
follicular ameloblastoma.
The background stroma characteristically is com-
posed of fibrous connective tissue that varies from
moderately to densely collagenized, typically pro-
ducing an eosinophilic background to the tumor
(Fig. 1). The fibroblastic cells of the stroma show a
tendency to parallel orientation of the nuclei, produc-ing a fascicular arrangement of the collagen. This
typical stroma allows rapid distinction of ameloblas-
toma from the ameloblastic fibroma and ameloblastic
fibro-odontoma, both of which show a loose, myxoid,
basophilic-staining connective tissue stroma that
lacks fasciculation and closely resembles dental pa-
pilla. The epithelial component of the neoplasm
proliferates in what seems to be disconnected islands,
strands, and cords within the collagenized fibrous
connective tissue stroma (see Fig. 1). A prominent
budding growth pattern often is seen, with small,rounded extensions of epithelium projecting from
larger islands, recapitulating the various stages of
enamel organ formation (Fig. 2). The islands, strands,
and cords may vary considerably in size, but regard-
less of size, they tend to show a distinctive color
gradation in their staining pattern when viewed under
low magnification (see Fig. 1). They stain darkly
basophilic on the periphery, whereas the cells in the
central portion of the proliferating epithelium show a
difference in color (see Fig. 1). The color seen in the
central portions is dependent on the specific subtype
of ameloblastoma under observation. On closer ex-amination at high-power magnification, the darkly
staining periphery is composed of tall columnar cells
Fig. 1. The ameloblastoma grows in disconnected islands,
strands, and cords within a background stroma of moderate
to densely collagenized fibrous connective tissue. This setup
produces an eosinophilic background color. There is pro-
minent color gradation between the peripheral and central
cells of the epithelial proliferation (hematoxylin-eosin, ori-
ginal magnification 5).
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with hyperchromatic nuclei (Fig. 3). The nuclei tend
to be round to oval in shape, and the nuclei of
adjacent cells are in roughly the same location within
the cytoplasm. This setup produces a characteristic
palisading pattern. The palisaded nuclei in many
areas seem to be pulled back from the basement
membrane area of the cell, and a small clear vacuole
can be seen between the nucleus and the basement
membrane (see Fig. 3). This peripheral layer of tallcolumnar cells with hyperchromasia, reverse polarity
of the nuclei, and subnuclear vacuole formation
mimic the normal embryologic development of the
tooth bud at the stage of enamel matrix production.
These classic features of ameloblastoma originally
were described by Vickers and Gorlin [21] in 1970.
Focally in many ameloblastomas, the proliferating
epithelium is seen to exert an inductive effect on the
surrounding connective tissue stroma. In these areas,
a zone of hyalinization of the collagen is present immediately adjacent to the epithelium. Fibroblasts
are almost totally absent within the zone of hyalin-
ization (Fig. 4). It is theorized that the ameloblastic
epithelium, in an attempt to complete its embryologic
function and produce enamel matrix, signals the
connective tissue to induce dentin formation; how-
ever, the fibroblastic cells in the connective tissue
are unable to differentiate into odontoblasts, a re-
quired step in dentin and enamel formation. The hya-
linized zone most likely represents the end result of
this blockade in the normal embryologic sequenceof odontogenesis.
Follicular ameloblastoma
As previously noted, the follicular type of amelo-
blastoma is the most commonly encountered variant
[1]. In this histologic subtype, all of the core features
of ameloblastoma are typically present. The follicular
ameloblastoma tends to grow primarily in islands,
however, and the cords and strands are less promi-
nently present (Fig. 5). The distinguishing feature is
the nature of the epithelial cells found in the center of the proliferating islands. The central cells are typically
polyhedral to spindle shaped. When spindle shaped,
they often have angular nuclei and poorly defined
cytoplasm, with delicate fibrillar cytoplasmic pro-
cesses that contact adjacent cells (Fig. 6). This setup
Fig. 3. There is a peripheral layer of tall columnar cells with
palisaded, hyperchromatic nuclei. The nuclei are round to
oval and are palisaded away from the basement membrane.
A subnuclear vacuole is present between the nucleus and
basement membrane (hematoxylin-eosin, original magnifi-
cation 20).
Fig. 4. The epithelium exerts an inductive effect on the sur-
rounding connective tissue stroma. There is a zone of hypo-
cellular, hyalinized collagen surrounding the neoplastic
epithelium (hematoxylin-eosin, original magnification 10).
Fig. 2. A prominent budding growth patter is present, and
rounded extensions of the epithelium recapitulate enamel
organ morphology (hematoxylin-eosin, original magnifica-
tion 10).
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produces a loosely cohesive meshwork that closely
simulates the stellate reticulum seen in the developing
enamel organ (Fig. 7). The central cells stain weakly
basophilic to amphophilic when compared with the
hyperchromatic columnar cells at the periphery, pro-
ducing a characteristic color gradation. Clear areas
between the central cells are also usually present,
emphasizing the color gradation (see Fig. 7). Theislands of tumor in the follicular ameloblastoma can
enlarge to sufficient size that central cystic degenera-
tion is seen (Fig. 8). This fairly common characteristic
of follicular ameloblastoma is less prominently pres-
ent in many of the other histologic subtypes.
Acanthomatous ameloblastoma
The acanthomatous ameloblastoma may closely
resemble the follicular type. As a rule, it shows the
core features common to most ameloblastomas. Like
the follicular ameloblastoma, it also tends to grow
primarily in an island-like pattern (Fig. 9). It differs
from the follicular ameloblastoma in the nature of thecentral cells within the tumor islands. In the acan-
thomatous ameloblastoma, squamous cells replace
the stellate reticulum-like cells (Fig. 10). The squa-
mous cells nearly always show a tendency to kera-
tinization in the most central portions of the tumor
Fig. 6. Follicular ameloblastoma. The cells in the center of
the tumor islands are spindle- to angular-shaped, simulating
stellate reticulum. There is a prominent color gradation
between peripheral and central cells (hematoxylin-eosin,
original magnification 20).
Fig. 7. Follicular ameloblastoma. An island of tumor cells
simulates enamel organ formation at the bud stage of odon-
togenesis. There is a loosely cohesive meshwork in the center
of the epithelial island that simulates stellate reticulum and a
peripheral columnar layer that simulates inner enamel epi-
thelium (hematoxylin-eosin, original magnification 20).
Fig. 5. Follicular ameloblastoma. The cells in the center of
the tumor islands are spindle- to angular-shaped, simulating
stellate reticulum. They have poorly defined cytoplasm with
delicate fibrillar cytoplasmic processes that contact adjacent
cells (hematoxylin-eosin, original magnification 20).
Fig. 8. Follicular ameloblastoma. An enlarging island of
tumor with early central cystic degeneration. This feature
commonly is seen (hematoxylin-eosin, original magnifica-
tion 10).
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islands (Fig. 11). Parakeratin typically is seen. This
effect produces a distinctive pink color change com-
pared with the deeply basophilic staining maintained
in the peripheral columnar cells (see Fig. 10). A layer
of stellate reticulum-like cells that separates the
peripheral columnar cells from the central squamous
areas often is seen (see Fig. 9; Fig. 12). This setup
often produces a triple-layer color pattern of red(central squamous cells), white (stellate reticulum-
like areas), and blue (peripheral columnar cells) (see
Fig. 12). Central cystic change can be seen in larger
tumor islands.
Granular cell ameloblastoma
The granular cell ameloblastoma is a relatively
rare histologic subtype, and in most instances, it is
found as an admixture with other histologic patterns,
particularly the follicular subtype [1,19]. For this
reason, it also shows the core histologic features
common to most ameloblastomas. The defining char-acteristic of granular cell ameloblastoma is the pres-
ence of granular cells in the central portion of the
epithelial islands, stands, and cords (Fig. 13). The
granular cells tend to be large and have an oval to
Fig. 10. Acanthomatous ameloblastoma. Squamous cells
replace the stellate reticulum-like cells, with a tendency to
keratinization. The prominent color gradation is present, but
the central areas show an eosinophilic color (hematoxylin-
eosin, original magnification 10).
Fig. 11. Acanthomatous ameloblastoma. Parakeratinization
of the central cells in the tumor islands is present. This effect
produces a characteristic pink color to the center of the
islands that contrasts the basophilic staining periphery
(hematoxylin-eosin, original magnification 5).
Fig. 12. Acanthomatous ameloblastoma. A layer of stellate
reticulum-like cells is seen separating the peripheral co-
lumnar cells from the central squamous area. This effect
produces a prominent red, white, and blue appearance (he-
matoxylin-eosin, original magnification 10).
Fig. 9. Acanthomatous ameloblastoma growing in an island-
like pattern. There are varying sizes of the tumor islands,
and there is typical eosinophilic staining of the fibrous
connective tissue stroma (hematoxylin-eosin, original mag-
nification 5).
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polyhedral outline. The nucleus is displaced to the
periphery of the cells. Prominent coarse granules
pack and distend the cytoplasm, imparting the dis-
tinctive appearance responsible for the name of these
cells (Fig. 14). The granular cells sometimes show a
sharply delineated cell border, but most often the cell
membranes are poorly demarcated, and the cytoplasm
of adjacent cells merges imperceptibly. The cytoplas-
mic granules tend to stain weakly eosinophilic, pro-
ducing a prominent color change compared with thestaining of the peripheral columnar cells. This eosino-
philic staining is typically less dramatic than that
seen in the acanthomatous ameloblastoma, however.
A thin rim of stellate reticulum-like cells that sepa-
rates the granular cells from the peripheral columnar
layer may or may not be present. Occasionally,
granular cell change also affects the peripheral co-
lumnar cells (see Fig. 14).
Basal cell ameloblastoma
The basal cell ameloblastoma is believed to be the
rarest histologic subtype [2]. It is reported to occur
primarily in a peripheral location but has been seen
intraosseously, albeit rarely [1]. It tends to grow in an
island-like pattern. The characteristic color gradation
seen in the other ameloblastomas is often difficult to
appreciate in the basal cell subtype (Fig. 15), because
basaloid-appearing cells rather than stellate reticu-lum-like cells occupy the central portion of the tumor
islands (Fig. 16). The basaloid cells tend to stain
deeply basophilic and are nearly equivalent in stain-
ing intensity with the peripheral layer of cells. The
cells in the central portion of the tumor islands may
be polyhedral to spindle shaped, but stellate reticu-
lum-like areas are notably absent (Fig. 17). The
typical cellular morphology and nuclear orientation
of the peripheral cells often are altered. The periph-
eral cells tend to be low columnar to cuboidal and
often do not demonstrate reverse nuclear polarity
with subnuclear vacuole formation. Hyperchroma-tism and palisading of the nuclei normally are re-
tained, however (see Fig. 17) This histologic subtype
shows a remarkable resemblance to basal cell carci-
noma, and published cases of intraoral basal cell car-
cinoma most likely are basal cell ameloblastomas.
Fig. 14. Granular cell ameloblastoma. Oval to polyhedral
cells with prominent coarse granules pack and distend the
cytoplasm, imparting the distinctive appearance that is re-
sponsible for the name of these cells. Individual cell borders
often are poorly delineated, and the cytoplasm of adjacent
cells merge. The granular cell change has extended to in-
volve the peripheral columnar cell layer (hematoxylin-eosin,
original magnification 20).
Fig. 15. Basal cell ameloblastoma growing in a predomi-
nantly island-like pattern. The typical color gradation is
more difficult to appreciate than in the other subtypes of
ameloblastoma, although a peripheral columnar cell layer is
present (hematoxylin-eosin, original magnification 5).
Fig. 13. Granular cell ameloblastoma growing in the typi-
cal island-like pattern. There are large, pink staining cells
in the center of the tumor islands (hematoxylin-eosin, origi-
nal magnification 5).
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Desmoplastic ameloblastoma
The desmoplastic ameloblastoma shows some
variation from the typical core characteristics dem-
onstrated by the other histologic subtypes. This type
of ameloblastoma characteristically is found in a
dense collagen stroma that may appear hyalinized
and hypocellular (Fig. 18). The desmoplastic amelo-
blastoma has a greater tendency to grow in thinstrands and cords of epithelium rather than in an
island-like pattern (Fig. 19). The epithelial prolifera-
tion almost seems to be squeezed out by the dense
hyalinized stroma. Central cells are often scant in the
epithelial proliferation, and the cells making up the
periphery of the strands and cords often are flattened
or cuboidal rather than tall columnar in appearance
(Fig. 20). Reverse polarity of nuclei and subnuclear
vacuole formation may be difficult to recognize.
Most desmoplastic ameloblastomas display occa-
sional classic islands of follicular ameloblastoma
among the predominant strands and cords (Fig. 21).
Without these classic islands of ameloblastoma, thediagnosis can be difficult.
Plexiform ameloblastoma
The plexiform ameloblastoma is distinct from the
other histologic subtypes in that it often lacks many
Fig. 17. Basal cell ameloblastoma. A tumor island with
spindle-shaped central cells and a more clearly delineated
peripheral, hyperchromatic layer outlining the tumor island.
There is an absence of stellate reticulum-like areas. There is
a marked resemblance to basal cell carcinoma (hematoxylin-
eosin, original magnification 20).
Fig. 18. Desmoplastic ameloblastoma showing predomi-
nantly islands but also strands and thin cords of epithelium
embedded in a dense, hypocellular, and hyalinized fibrous
stroma (hematoxylin-eosin, original magnification 2).
Fig. 19. Desmoplastic ameloblastoma. Higher magnifica-
tion details the cord and strand-like growth that is char-
acteristic of this histologic subtype (hematoxylin-eosin,
original magnification 5).
Fig. 16. Basal cell ameloblastoma. Basaloid-appearing cells
rather than stellate reticulum-like cells occupy the central
portion of the tumor islands (hematoxylin-eosin, original
magnification 10).
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of the core histopathologic characteristics that define
the other variants. The plexiform ameloblastoma
usually shows a sparse fibrous connective tissue
stroma (Fig. 22). This stroma is often loose and
myxoid in appearance. The plexiform ameloblastoma
shows a predominance of a strand-like growth pattern
with a strong tendency to interconnection of theneoplastic epithelium (see Fig. 22). This setup tends
to produce a plexiform network of interanastamos-
ing epithelium that gives this subtype its name (see
Fig. 22). The cellular growth pattern most closely
simulates the dental lamina stage of normal odonto-
genesis, before enamel organ morphodifferentiation
and histodifferentiation occur. The proliferating epi-
thelial strands often are composed of a bilayer of
cuboidal to low columnar cells (Fig. 23). Because the
proliferating epithelium simulates the dental lamina
before enamel organ differentiation, reverse polarity
of the nuclei with subnuclear vacuole formation is
often difficult to identify (see Fig. 23). Differentia-tion toward the bud stage of odontogenesis may be
evidenced by rounded nodules of epithelium, and a
peripheral row of low columnar cells proliferates off
of the dental lamina-like strands (Fig. 24). In other
Fig. 21. Desmoplastic ameloblastoma. In this area, thin
strands of typical desmoplastic ameloblastoma are seen ad-
jacent to islands of classic ameloblastoma, facilitating the di-
agnosis (hematoxylin-eosin, original magnification 20).
Fig. 22. Plexiform ameloblastoma is characterized by a
sparse fibrous connective tissue stroma that is loose and
myxoid in appearance. The tumor grows predominantly in
a strand-like pattern with a strong tendency to interconnec-
tion of the neoplastic epithelium, producing a plexiform
network (hematoxylin-eosin, original magnification 2).
Fig. 23. Plexiform ameloblastoma. The proliferating epithe-
lium often is composed of a bilayer of cuboidal to low
columnar cells, closely simulating the dental lamina stage
of odontogenesis. There is a loose background stroma and
an absence of reverse polarity of the nuclei (hematoxylin-
eosin, original magnification 10).
Fig. 20. Desmoplastic ameloblastoma. An area of island-like
growth is seen. The cells at the periphery are flattened and
squamoid to cuboidal in appearance rather than columnar.
Reverse polarity of nuclei and subnuclear vacuole formation
in the peripheral cells are not clearly evident (hematoxylin-
eosin, original magnification 20).
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areas, the lamina-like strands may expand because of
proliferation of epithelial cells between the bilayers
(Fig. 25). The proliferating cells may resemble stel-
late reticulum, or they may be round to polyhedral
in shape. Areas of sheet-like growth of the epithe-
lium also may be a significant component of the plexi-
form subtype.
Growth patterns and treatment implications
Although the importance of the specific histologic
subtype of ameloblastoma in the determination of
biologic behavior is open to debate, it is well docu-
mented that the overall growth pattern of the neo-
plasm is important [1,3,10,12,20]. It has significant
implications in treat ment decisions and the incidence
of recurrence [12]. The growth pattern of intra-
osseous ameloblastoma can be classified into two
broad categories: (1) conventional ameloblastoma and
(2) unicystic ameloblastoma [10]. More than 90%of ameloblastomas are classified as the conventional
type [1,3].
Conventional ameloblastoma
In the conventional ameloblastoma, the neoplasm
grows in its typical island, strand, and cord-like
patterns but presents surgically as a largely solid tu-
mor mass within the bone [10]. In areas where is-
lands of ameloblastic epithelium attain large size,
cystic degeneration in the center of the tumor islandsoften may be seen (Fig. 26). This feature can be a
prominent component of the neoplastic proliferation,
to the point that cyst-like areas may be identified
grossly at the time of surgery [2,10]. The histopatho-
logic diagnosis of cystic ameloblastoma sometimes
is applied to lesions that show this feature. Such a
diagnosis may lead to confusion with the unicystic
type of ameloblastoma. Cystic degeneration in an
otherwise solid (conventional) ameloblastoma does
not alter the prognosis or the incidence of recurrence,
and it should not affect surgical treatment decisions
[10]. As befitting a neoplasm with locally aggres-sive behavior, conventional ameloblastoma typically
shows irregular infiltration of tumor into the sur-
Fig. 25. Plexiform ameloblastoma. The lamina-like strands
expanded because of the proliferation of cells between the
bilayers. These areas show some resemblance to stellate re-
ticulum (hematoxylin-eosin, original magnification 10).
Fig. 26. Whole-mount view of conventional ameloblastoma
of the mandible. The tumor has involved the body, angle,
and coronoid process. Solid areas of tumor are present at
the junction between the body and ascending ramus. Areas
of cystic degeneration that would be grossly evident at sur-
gery can be seen involving the coronoid process, lower bor-
der, and angle areas (hematoxylin-eosin, scanning view of
whole mount preparation).
Fig. 24. Plexiform ameloblastoma. Differentiation toward
the bud stage of odontogenesis is evidenced by rounded
nodules of epithelium, and a peripheral row of low colum-
nar cells proliferates off of the dental lamina-like strands
(hematoxylin-eosin, original magnification 20).
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rounding bone and soft tissues (Fig. 27). Islands of
neoplasm at times can be found far from the main
tumor mass and often are seen within trabecular
spaces that are separate from the main tumor mass
and surrounded by an intact bony rim [10]. These
separate tumor islands may hinder the surgeon’s
ability to completely remove the neoplasm when
conservative forms of therapy are used [10]. For this
reason, block resection is often the treatment of
choice, and surgical margins generally are established
at a distance of at least 1 cm from the clinical or radiographic boundary of the neoplasm [1–3,10,
12,20]. Even with this 1-cm margin of error, a sig-
nificant recurrence rate is reported (eg, 17.7% in one
study) [1]. As would be expected, treatment of
conventional ameloblastoma by curettage alone is
associated with a markedly increased incidence of
recurrence when compared with the recurrence rate
after block resection [10,12,22,23]. Some studies
have reported a 100% recurrence rate for ameloblas-
tomas that are treated only by curettage [13,19];
however, most studies report lower rates, rangingfrom 50% to greater than 90% [3,6,7,9,10,12,19,
20,22]. If a more conservative surgical option than
block resection is chosen, mechanical or chemical
fulguration of the margin often is included in the sur-
gical treatment plan to reduce the chance of recur-
rence [20,23]. Peripheral ostectomy using a bone bur
is reported to provide an additional margin of safety,
and in some studies no recurrences were reported
after up to 15 years of follow-up [20]. Cryotherapy of
the margins has been advocated, and one case reports
no recurrence at 5 years after treatment [12]. Treat-
ment with chemical agents, including formaldehyde,has been tried, but specific recurrence rates with
chemical fulguration have not been reported [10,23].
Unicystic ameloblastoma
The second and far less frequent growth pattern
seen in the intraosseous ameloblastoma is the uni-
cystic type. This growth pattern is seen in approxi-
mately 6% of ameloblastomas [1]. It tends to occur ina younger population (average age in one large study,
22.1 years) [1] compared with the patient population
with conventional ameloblastomas [3,8,10,12,14,20,
22,24,25]. A high percentage of these lesions are
associated with an impacted tooth, and the most
commonly cited provisional diagnosis is dentigerous
cyst. Cystic areas nearly always are noted grossly at
the time of surgery [10,24]. Recognition of this
growth pattern is important, because it is well ac-
cepted that the unicystic type has a considerably bet-
ter overall prognosis and a much reduced incidence of recurrence compared with conventional ameloblas-
toma [10,22,24]. Although oral and maxillofacial
pathologists accept the concept of unicystic amelo-
blastoma, considerable debate exists regarding how it
should be defined. The unicystic ameloblastoma
grows predominantly as a cystic lesion (Fig. 28).
The epithelium lining the cystic cavity of the neo-
plasm shows typical cytomorphologic features that
are recognizable as ameloblastoma, with a basal cell
layer composed of columnar cells displaying hy-
perchromatic, palisaded nuclei (see Fig. 28 inset).
Reverse polarity of the nuclei is present, and a sub-nuclear vacuole usually is noted between the base-
Fig. 28. Unicystic ameloblastoma. The ameloblastoma
shows a cystic architecture with the typical ameloblastic
changes confined to the cyst-lining epithelium. The arrow
indicates the area enlarged in the inset at lower right (hema-
toxylin-eosin, original magnification 2). ( Inset ) Amelo-
blastic epithelium with hyperchromatic palisaded basal cell
layer, thin layer of stellate reticulum-like cells, and abrupt
transition to a thin parakeratinizing luminal surface (hema-
toxylin-eosin, original magnification 10).
Fig. 27. Conventional intraosseous ameloblastoma. The neo-
plasm shows infiltration into the surrounding bone (hema-
toxylin-eosin, original magnification 2).
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ment membrane and nucleus. A thin overlying layer
of stellate reticulum-like cells is seen. A luminal
parakeratin layer may or may not be present (see
Fig. 28 inset). When keratinization is present, an
abrupt transition from the stellate reticulum-like layer
usually is observed. In some instances, the ameloblas-tic epithelium may be proliferative, with extension of
the ameloblastic epithelium into the lumen of the
cystic cavity (Fig. 29). This feature has been termed
intraluminal proliferation, and in many instances, the
intraluminal growth resembles the plexiform type of
ameloblastoma. Thus, some lesions have been re-
ferred to as plexiform unicystic ameloblastoma [10].
There seems to be general agreement that as long as
the ameloblastic characteristics are confined to the
lining epithelial layers or the ameloblastic epithelial
proliferation is strictly intraluminal, conservative ther-apy such as enucleation or thorough curettage, should
allow for excellent long-term results and a recurrence
rate that approaches zero [10]. The difficulty in
defining the unicystic ameloblastoma occurs when
there is growth of the ameloblastic epithelium into
the connective tissue wall of the otherwise cystic
neoplasm. The epithelium may remain in direct con-
tact with the cystic ameloblastic epithelium (Fig. 30),
or it may appear as separate islands of tumor in
the connective tissue wall (Fig. 31). This characteristic
is termed mural (or intramural) growth and is the
point of contention in the definition of unicysticameloblastoma. Some pathologists allow a diagnosis
of unicystic ameloblastoma in the presence of mural
tumor proliferation. They argue that as long as the
proliferation is limited to the connective tissue of the
cyst wall and has not penetrated the surrounding
bone, the lesion can be enucleated safely without
leaving behind residual islands of tumor that might
eventuate in a recurrence. They accept enucleation or
curettage as an acceptable treatment for these lesions.
Other pathologists reject this concept and argue that any amount of mural proliferation constitutes local
invasive growth, and the lesion should be classified
Fig. 29. Unicystic ameloblastoma. A cyst-like architecture
is present and ameloblastic changes can be seen in the cyst-
lining epithelium. Intraluminal proliferation is seen as a
large nodular mass of plexiform ameloblastoma confined
to the lumen of the cyst without involvement of the con-
nective tissue wall (hematoxylin-eosin, original magnifica-
tion 0.63).
Fig. 30. Ameloblastoma with mural growth. Ameloblastic
epithelium infiltrates the connective tissue of the cyst wall.
The infiltrating ameloblastic epithelium remains in direct
continuity with the ameloblastic epithelium lining the cystic
lesion. The cyst lumen is seen at the bottom (hematoxylin-
eosin, original magnification 5).
Fig. 31. Ameloblastoma with mural growth. Ameloblastic
epithelium infiltrates the connective tissue of the cyst wall
as separate islands without direct continuity to the amelo-
blastic epithelium lining the cyst. There are islands of tumor
deep within the connective tissue at a significant distance
from other surrounding islands of tumor. The cyst lumen is
present at the bottom left (hematoxylin-eosin, original mag-
nification 5).
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as a conventional ameloblastoma. These pathologists
note that if mural proliferation is present and the
lesion has been treated by enucleation or curettage,
one never can be certain that tumor has not penetrated
the surrounding bone, because the bony margin has
not been examined microscopically. In this situation,it is expected that recurrence would be seen in a
significant number of cases diagnosed as unicystic
ameloblastoma, resulting in a diagnostic ‘‘catch-22.’’
To definitively establish a lesion as a unicystic
ameloblastoma, complete microscopic evaluation of
the bony margin surrounding the lesion must be done,
in essence requiring a block resection of the lesion;
however, the whole point of making a diagnosis of
unicystic ameloblastoma is to afford a more conser-
vative treatment approach (ie, enucleation or curett-
age rather than block resection). Statistics on theincidence of recurrence of lesions diagnosed as uni-
cystic ameloblastoma seem to indicate that the reality
of treatment lies somewhere between these two argu-
ments. The recurrence rate for unicytstic ameloblas-
tomas is not zero but is reported to range from 10.7%
to almost 25% [3,14,20]. This rate is much lower than
the reported recurrence rate for conventional amelo-
blastoma that are treated only by enucleation or
curettage [1,3,14,22]. The variation in recurrence
rates probably reflects classification of some conven-
tional ameloblastomas as unicystic, inflating what
might be an overall lower recurrence rate for trulyunicystic tumors [26]. To address the inconsistency in
definition, some pathologists have refined their defi-
nition of unicystic ameloblastoma and accept only a
strictly unilocular lesion on radiograph as a true
unicystic ameloblastoma. The rationale for this view
is that multilocular lesions are reported to show a
much higher incidence of recurrence when compared
with the recurrence rate of unilocular lesions [12].
Other investigators continue to accept multilocular-
appearing radiographic lesions as unicystic amelo-
blastoma if the histologic features are consistent. Allresearchers tend to agree, however, that an accurate
diagnosis of unicystic ameloblastoma only can be
made by thorough sampling of the entire specimen
[14,20,22]. For this reason, a definitive diagnosis of
unicystic ameloblastoma never can be made based on
an incisional biopsy. The possibility of a unicystic
lesion might be inferred from an incisional biopsy,
and this finding might influence the surgical treat-
ment plan.
Treatment implications
Treatment decisions for ameloblastoma are based
on the individual patient situation and the best judg-
ment of the surgeon. The surgical plan should be
influenced strongly by whether the lesion involves
the mandible or maxilla. Maxillary lesions behave
distinctly differently from mandibular lesions [3,10].
The difference in cancellous bone percentage be-
tween the maxilla and mandible is cited as therationale for this variation [1,20]. The higher cancel-
lous bone percentage in the maxilla facilitates the
spread of the ameloblastoma, whereas the density of
the cortical plates in the mandible tends to limit
spread of the neoplasm [10,20]. The location of the
maxilla in the center of the maxillofacial complex
allows greater ease of extension of the ameloblastoma
into vital structures, sinus, orbit, and skull base,
resulting in increased morbidity and mortality rates
[3,10–12]. Regardless of which jaw is involved, once
an ameloblastoma has recurred, retreatment becomesmore challenging [12]. Radical retreatment typically
is performed. In the mandible, this approach has
proved to be successful in approximately 80% of
cases [12]. Retreatment of maxillary lesions is more
difficult, however [13]. Multiple recurrences, even
with radical retreatment, are common [12,13]. Once a
maxillary ameloblastoma recurs, the lesion often is
found to invade adjacent critical areas. Several
reports of extension of maxillary ameloblastoma to
the brain, resulting in death, have been noted [6,9,12].
Aggressive initial treatment of maxillary ameloblas-
toma, even for suspected unicystic lesions, is pro-moted fiercely [6,10,12,13,27]. One study [27]
reported a 5-year survival rate of only 16% when
the initial treatment for maxillary ameloblastoma was
limited resection.
Summary
Ameloblastoma is the most significant odonto-
genic neoplasm of concern for oral and maxillofacialsurgeons. It shows a wide variety of clinical and
radiographic presentations and can be encountered in
any area of the jaws. Six histopathologic subtypes
are recognized, and the specific histopathologic fea-
tures of each are detailed and discussed. Although
the histopathologic pattern may have implications for
the likelihood of recurrence, it should not affect
treatment decisions. The growth pattern of the neo-
plasm, categorized as conventional or unicystic, is
more important than the histopathologic subtype.
The growth pattern and the specific jaw (maxilla
versus mandible) in which the tumor is found arethe most important factors when considering treat-
ment options.
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References
[1] Reichart PA, Philipsen HP, Sonner S. Ameloblastoma:
biological profile of 3677 cases. Eur J Cancer B Oral
Oncol 1995;31B(2):86 – 99.
[2] Neville BW, Damm DD, Allen CM, Bouquot JE. Oraland maxillofacial pathology. 2nd edition. Philadelphia:
WB Saunders; 2002. p. 611–9.
[3] Kessler HP, Schwartz-Dabney C, Ellis III E. Recurrent
left mandibular enlargement. J Contemp Dent Pract
2003;3(4):127–37.
[4] Wettan HL, Patella PA, Freedman PD. Peripheral ame-
loblastoma: review of the literature and report of recur-
rence as severe dysplasia. J Oral Maxillofac Surg 2001;
59(7):811–5.
[5] Philipsen HP, Reichart PA, Nikai H, Takata T, Kudo Y.
Peripheral ameloblastoma: biological profile based on
160 cases from the literature. Oral Oncol 2001;37(1):
17–27.[6] Zwahlen RA, Gratz KW. Maxillary ameloblastomas:
a review of the literature and of a 15-year database.
J Craniomaxillofac Surg 2002;30(5):273– 9.
[7] Henderson JM, Sonnet JR, Schlesinger C, Ord RA.
Pulmonary metastasis of ameloblastoma: case report
and review of the literature. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 1999;88(2):170–6.
[8] Ord RA, Blanchaert Jr RH, Nikitakis NG, Sauk JJ.
Ameloblastoma in children. J Oral Maxillofac Surg
2002;60(7):762–71.
[9] Tsaknis PJ, Nelson JF. The maxillary ameloblas-
toma: an analysis of 24 cases. J Oral Surg 1980;
38(5):336–42.
[10] Gardner DG. A pathologist’s approach to the treatment
of ameloblastoma. J Oral Maxillofac Surg 1984;42(3):
161–6.
[11] Schafer DR, Thompson LDR, Smith BC, Wenig BM.
Primary ameloblastoma of the sinonasal tract: a clini-
copathologic study of 24 cases. Cancer 1998;82(4):
667–74.
[12] Feinberg SE, Steinberg B. Surgical management of
ameloblastoma: current status of the literature. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod 1996;
81(4):383–8.
[13] Sehdev MK, Huvos AG, Strong EW, Gerold FP, WillisGW. Ameloblastoma of maxilla and mandible. Cancer
1974;33(2):324–33.
[14] Philipsen HP, Reichart PA. Unicystic ameloblastoma:
a review of 193 cases from the literature. Oral Oncol
1998;34(5):317–25.
[15] Kawai T, Kishino M, Hiranuma H, Sasai T, Ishida T.
A unique case of desmoplastic ameloblastoma of the
mandible: report of a case and brief review of the
English language literature. Oral Surg Oral Med OralPathol Oral Radiol Endod 1999;87(2):258–63.
[16] Keszler A, Paparella ML, Dominguez FV. Desmoplas-
tic and non-desmoplastic ameloblastoma: a compara-
tive clinicopathological analysis. Oral Dis 1996;2(3):
228–31.
[17] Eversole LR, Leider AS, Hansen LS. Ameloblastomas
with pronounced desmoplasia. J Oral Maxillofac Surg
1984;42(11):735–40.
[18] Ashman SG, Corio RL, Eisele DW, Murphy MT. Des-
moplastic ameloblastoma: a case report and literature
review. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1993;75(4):479– 82.
[19] Hartman KS. Granular-cell ameloblastoma. Oral SurgOral Med Oral Pathol Oral Radiol Endod 1974;38(2):
241–53.
[20] Gardner DG. Some current concepts on the pathology
of ameloblastomas. Oral Surg Oral Med Oral Pathol
Oral Radiol Endod 1996;82(6):660–9.
[21] Vickers RA, Gorlin RJ. Ameloblastoma: delineation of
early histopathologic features of neoplasia. Cancer
1970;26(3):699–710.
[22] Li TJ, Kitano M, Arimura K, Sugihara K. Recurrence
of unicystic ameloblastoma: a case report and review
of the literature. Arch Pathol Lab Med 1998;122(4):
371–4.
[23] Byrne MP, Kosmala RL, Cunningham MP. Ameloblas-
toma with regional and distant metastases. Am J Surg
1974;128(1):91–4.
[24] Robinson L, Martinez M. Unicystic ameloblastoma:
a prognostically distinct entity. Cancer 1977;40(5):
2278–85.
[25] Regezi JA. Odontogenic cysts, odontogenic tumors,
fibroosseous, and giant cell lesions of the jaws. Mod
Pathol 2002;15(3):331– 41.
[26] Gardner DG. Critique of the 1995 review by Reichart
et al. of the biologic profile of 3677 ameloblastomas.
Oral Oncol 1999;35(4):443–9.
[27] Bredenkamp JK, Zimmerman MC, Mickel RA. Maxil-lary ameloblastoma: a potentially lethal neoplasm. Arch
Otolaryngol Head Neck Surg 1989;115(1):99– 104.
H.P. Kessler / Oral Maxillofacial Surg Clin N Am 16 (2004) 309–322322
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