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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: [email protected]

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 impacted 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,


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-


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,


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-


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-



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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-


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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