Oral Maxillofacial Surg Clin N Am 16 (2004) 309 322

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 odontogenic epithelial origin. It is the second most common
odontogenic neoplasm, and only odontoma outnumbers 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 ameloblastoma 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 ameloblastoma in black individuals [2,9], a large study
identifies Asians as the population with the greatest
number of affected patients [1]. Because sizeable

E-mail address: hkessler@tambcd.edu

numbers of cases are reported in every racial group,

race does not seem to be a significant defining demographic 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 mutations in the genetic material of cells that embryologically are preprogrammed for tooth development.
Environmental factors and individual patient variables (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 ameloblastoma 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]. Statistics 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 incidence 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 ameloblastoma in a number of cases that originate in the

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H.P. Kessler / Oral Maxillofacial Surg Clin N Am 16 (2004) 309322

maxilla [6]. Some studies label sinonasal areas as a

separate category when reviewing maxillary ameloblastomas, 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 uniformity 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 the
other 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 presenting 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 panoramic 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 encountered often. When visualized in CT images, lesions
that appear multilocular on plane films usually show
scalloping resorption of the delimiting cortical plates
rather 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 lucentopaque lesion that often 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 mandibular third molar is the most commonly involved tooth
[3,14]. Unilocular lesions associated with an impacted tooth also tend to be found in significantly
younger patients compared with patients with multilocular lesions [1]. A large proportion of the ameloblastomas reported in young children are found in
this clinical setting [8]. A mixed lucent-opaque radiographic 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 produce this mixed lucent-opaque pattern, however [16];
the remainder produce entirely radiolucent lesions.
Unlike the other types of ameloblastoma, the desmoplastic 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 predominant pattern that is present. The various subtypes
have been studied and analyzed extensively to determine 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 correlations
have prognostic implications or affect treatment decisions, 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 literature-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 recurrence at 29.5%. In contradistinction, the acanthomatous type of ameloblastoma showed only a 4.5%
recurrence rate. The plexiform subtype was intermediate 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 als study
[1], none of the desmoplastic cases recurred, but there
were 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 ameloblastoma [15,18]. Reichart et als 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 recurrent cases, with increased numbers of all the different
histologic subtypes, are necessary to confirm or refute
these statistics.

311

The background stroma characteristically is composed of fibrous connective tissue that varies from
moderately to densely collagenized, typically producing an eosinophilic background to the tumor
(Fig. 1). The fibroblastic cells of the stroma show a
tendency to parallel orientation of the nuclei, producing a fascicular arrangement of the collagen. This
typical stroma allows rapid distinction of ameloblastoma 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 papilla. 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 regardless 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 examination at high-power magnification, the darkly
staining periphery is composed of tall columnar cells

Core histologic features

On microscopic examination, most histologic variants of ameloblastoma show a core group of distinctive 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 similarity when these characteristics are compared among
the groups. Only the plexiform subtype shows significant variations from this core group of characteristics. Because the follicular subtype is the most
commonly encountered variant [1], some pathologists
believe that the acanthomatous, granular cell, basal
cell, and desmoplastic variants are subsets of the
follicular ameloblastoma.

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 prominent color gradation between the peripheral and central
cells of the epithelial proliferation (hematoxylin-eosin, original magnification 5).

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Fig. 2. A prominent budding growth patter is present, and

rounded extensions of the epithelium recapitulate enamel
organ morphology (hematoxylin-eosin, original magnification 10).

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 tall
columnar 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.

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 magnification 20).

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 hyalinization (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; however, the fibroblastic cells in the connective tissue
are unable to differentiate into odontoblasts, a required step in dentin and enamel formation. The hyalinized zone most likely represents the end result of
this blockade in the normal embryologic sequence
of odontogenesis.
Follicular ameloblastoma
As previously noted, the follicular type of ameloblastoma 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 prominently 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 processes that contact adjacent cells (Fig. 6). This setup

Fig. 4. The epithelium exerts an inductive effect on the surrounding connective tissue stroma. There is a zone of hypocellular, hyalinized collagen surrounding the neoplastic
epithelium (hematoxylin-eosin, original magnification 10).

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313

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. 7. Follicular ameloblastoma. An island of tumor cells

simulates enamel organ formation at the bud stage of odontogenesis. 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 epithelium (hematoxylin-eosin, original magnification 20).

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, producing a characteristic color gradation. Clear areas
between the central cells are also usually present,
emphasizing the color gradation (see Fig. 7). The
islands of tumor in the follicular ameloblastoma can
enlarge to sufficient size that central cystic degeneration is seen (Fig. 8). This fairly common characteristic
of follicular ameloblastoma is less prominently present in many of the other histologic subtypes.

Acanthomatous ameloblastoma

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).

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 the
central cells within the tumor islands. In the acanthomatous ameloblastoma, squamous cells replace
the stellate reticulum-like cells (Fig. 10). The squamous cells nearly always show a tendency to keratinization in the most central portions of the tumor

Fig. 8. Follicular ameloblastoma. An enlarging island of

tumor with early central cystic degeneration. This feature
commonly is seen (hematoxylin-eosin, original magnification 10).

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Fig. 9. Acanthomatous ameloblastoma growing in an islandlike pattern. There are varying sizes of the tumor islands,
and there is typical eosinophilic staining of the fibrous
connective tissue stroma (hematoxylin-eosin, original magnification 5).

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).

islands (Fig. 11). Parakeratin typically is seen. This

effect produces a distinctive pink color change compared 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 reticulumlike areas), and blue (peripheral columnar cells) (see
Fig. 12). Central cystic change can be seen in larger
tumor islands.

Granular cell ameloblastoma

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 (hematoxylineosin, original magnification 10).

Fig. 12. Acanthomatous ameloblastoma. A layer of stellate

reticulum-like cells is seen separating the peripheral columnar cells from the central squamous area. This effect
produces a prominent red, white, and blue appearance (hematoxylin-eosin, original magnification 10).

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 characteristic of granular cell ameloblastoma is the presence 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

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315

seen in the acanthomatous ameloblastoma, however.

A thin rim of stellate reticulum-like cells that separates the granular cells from the peripheral columnar
layer may or may not be present. Occasionally,
granular cell change also affects the peripheral columnar cells (see Fig. 14).
Basal cell ameloblastoma

Fig. 13. Granular cell ameloblastoma growing in the typical island-like pattern. There are large, pink staining cells
in the center of the tumor islands (hematoxylin-eosin, original magnification 5).

polyhedral outline. The nucleus is displaced to the

periphery of the cells. Prominent coarse granules
pack and distend the cytoplasm, imparting the distinctive 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 cytoplasmic granules tend to stain weakly eosinophilic, producing a prominent color change compared with the
staining of the peripheral columnar cells. This eosinophilic staining is typically less dramatic than that

Fig. 14. Granular cell ameloblastoma. Oval to polyhedral

cells with prominent coarse granules pack and distend the
cytoplasm, imparting the distinctive appearance that is responsible 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 involve the peripheral columnar cell layer (hematoxylin-eosin,
original magnification 20).

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 reticulum-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 staining 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 reticulum-like areas are notably absent (Fig. 17). The
typical cellular morphology and nuclear orientation
of the peripheral cells often are altered. The peripheral cells tend to be low columnar to cuboidal and
often do not demonstrate reverse nuclear polarity
with subnuclear vacuole formation. Hyperchromatism and palisading of the nuclei normally are retained, however (see Fig. 17) This histologic subtype
shows a remarkable resemblance to basal cell carcinoma, and published cases of intraoral basal cell carcinoma most likely are basal cell ameloblastomas.

Fig. 15. Basal cell ameloblastoma growing in a predominantly 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).

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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).

Fig. 18. Desmoplastic ameloblastoma showing predominantly islands but also strands and thin cords of epithelium
embedded in a dense, hypocellular, and hyalinized fibrous
stroma (hematoxylin-eosin, original magnification 2).

Desmoplastic ameloblastoma

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 occasional classic islands of follicular ameloblastoma
among the predominant strands and cords (Fig. 21).
Without these classic islands of ameloblastoma, the
diagnosis can be difficult.

The desmoplastic ameloblastoma shows some

variation from the typical core characteristics demonstrated 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 ameloblastoma has a greater tendency to grow in thin
strands and cords of epithelium rather than in an
island-like pattern (Fig. 19). The epithelial proliferation almost seems to be squeezed out by the dense
hyalinized stroma. Central cells are often scant in the

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 (hematoxylineosin, original magnification 20).

Fig. 19. Desmoplastic ameloblastoma. Higher magnification details the cord and strand-like growth that is characteristic of this histologic subtype (hematoxylin-eosin,
original magnification 5).

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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 (hematoxylineosin, original magnification 20).

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 the
neoplastic epithelium (see Fig. 22). This setup tends
to produce a plexiform network of interanastamosing epithelium that gives this subtype its name (see
Fig. 22). The cellular growth pattern most closely
simulates the dental lamina stage of normal odonto-

Fig. 21. Desmoplastic ameloblastoma. In this area, thin

strands of typical desmoplastic ameloblastoma are seen adjacent to islands of classic ameloblastoma, facilitating the diagnosis (hematoxylin-eosin, original magnification 20).

317

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 interconnection of the neoplastic epithelium, producing a plexiform
network (hematoxylin-eosin, original magnification 2).

genesis, before enamel organ morphodifferentiation

and histodifferentiation occur. The proliferating epithelial 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). Differentiation 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. 23. Plexiform ameloblastoma. The proliferating epithelium 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 (hematoxylineosin, original magnification 10).

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plasm is important [1,3,10,12,20]. It has significant

implications in treatment decisions and the incidence
of recurrence [12]. The growth pattern of intraosseous 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

Fig. 24. Plexiform ameloblastoma. Differentiation toward

the bud stage of odontogenesis is evidenced by rounded
nodules of epithelium, and a peripheral row of low columnar cells proliferates off of the dental lamina-like strands
(hematoxylin-eosin, original magnification 20).

areas, the lamina-like strands may expand because of

proliferation of epithelial cells between the bilayers
(Fig. 25). The proliferating cells may resemble stellate reticulum, or they may be round to polyhedral
in shape. Areas of sheet-like growth of the epithelium also may be a significant component of the plexiform 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 documented that the overall growth pattern of the neo-

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 reticulum (hematoxylin-eosin, original magnification 10).

In the conventional ameloblastoma, the neoplasm

grows in its typical island, strand, and cord-like
patterns but presents surgically as a largely solid tumor mass within the bone [10]. In areas where islands of ameloblastic epithelium attain large size,
cystic degeneration in the center of the tumor islands
often 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 histopathologic 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 aggressive behavior, conventional ameloblastoma typically
shows irregular infiltration of tumor into the sur-

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 surgery can be seen involving the coronoid process, lower border, and angle areas (hematoxylin-eosin, scanning view of
whole mount preparation).

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319

Unicystic ameloblastoma

Fig. 27. Conventional intraosseous ameloblastoma. The neoplasm shows infiltration into the surrounding bone (hematoxylin-eosin, original magnification 2).

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 surgeons
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 significant 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 ameloblastomas that are treated only by curettage [13,19];
however, most studies report lower rates, ranging
from 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 surgical treatment plan to reduce the chance of recurrence [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]. Treatment with chemical agents, including formaldehyde,
has been tried, but specific recurrence rates with
chemical fulguration have not been reported [10,23].

The second and far less frequent growth pattern

seen in the intraosseous ameloblastoma is the unicystic type. This growth pattern is seen in approximately 6% of ameloblastomas [1]. It tends to occur in
a 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 accepted that the unicystic type has a considerably better overall prognosis and a much reduced incidence of
recurrence compared with conventional ameloblastoma [10,22,24]. Although oral and maxillofacial
pathologists accept the concept of unicystic ameloblastoma, 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 neoplasm shows typical cytomorphologic features that
are recognizable as ameloblastoma, with a basal cell
layer composed of columnar cells displaying hyperchromatic, palisaded nuclei (see Fig. 28 inset).
Reverse polarity of the nuclei is present, and a subnuclear 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 (hematoxylin-eosin, original magnification 2). (Inset) Ameloblastic epithelium with hyperchromatic palisaded basal cell
layer, thin layer of stellate reticulum-like cells, and abrupt
transition to a thin parakeratinizing luminal surface (hematoxylin-eosin, original magnification 10).

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H.P. Kessler / Oral Maxillofacial Surg Clin N Am 16 (2004) 309322

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 ameloblastic 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 referred 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 therapy 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 contact 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 unicystic
ameloblastoma. 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 cystlining epithelium. Intraluminal proliferation is seen as a
large nodular mass of plexiform ameloblastoma confined
to the lumen of the cyst without involvement of the connective tissue wall (hematoxylin-eosin, original magnification 0.63).

Fig. 31. Ameloblastoma with mural growth. Ameloblastic

epithelium infiltrates the connective tissue of the cyst wall
as separate islands without direct continuity to the ameloblastic 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 magnification 5).

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 (hematoxylineosin, original magnification 5).

H.P. Kessler / Oral Maxillofacial Surg Clin N Am 16 (2004) 309322

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 conservative treatment approach (ie, enucleation or curettage rather than block resection). Statistics on the
incidence of recurrence of lesions diagnosed as unicystic ameloblastoma seem to indicate that the reality
of treatment lies somewhere between these two arguments. The recurrence rate for unicytstic ameloblastomas 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 ameloblastoma that are treated only by enucleation or
curettage [1,3,14,22]. The variation in recurrence
rates probably reflects classification of some conventional ameloblastomas as unicystic, inflating what
might be an overall lower recurrence rate for truly
unicystic tumors [26]. To address the inconsistency in
definition, some pathologists have refined their definition 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 multilocularappearing radiographic lesions as unicystic ameloblastoma if the histologic features are consistent. All
researchers 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 treatment plan.
Treatment implications
Treatment decisions for ameloblastoma are based
on the individual patient situation and the best judg-

321

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 between the maxilla and mandible is cited as the
rationale for this variation [1,20]. The higher cancellous 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 becomes
more 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 ameloblastoma, even for suspected unicystic lesions, is promoted 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 odontogenic neoplasm of concern for oral and maxillofacial
surgeons. 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 features 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 neoplasm, 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 are
the most important factors when considering treatment options.

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