Ameloblastoma, the most common odontogenic tumor [1], closely resembles the epithelial part of the tooth germ: ameloblastomas may be locally aggressive, but do not metastasise. They may occur at any age, but cases in the first decade are rare and most of them are diagnosed between the ages of 30–60 years. Mostly, the mandible is involved. In the less often seen maxillary cases, the tumor may grow into the paranasal sinuses to attain a considerable size without causing any external deformity. Radiographically, ameloblastoma is a radiolucent lesion that usually is multilocular, the so-called soap bubble appearance, or unilocular with scalloped outlines (Fig. 3.1) [2]. Macroscopically, the tumors may be solid as well as cystic but mostly, both appearances occur together in a single lesion (Fig. 3.2). By microscopy, ameloblastomas basically consist of either anastomosing epithelial strands and fields or discrete epithelial islands. The former pattern is referred to as plexiform type, the latter as follicular type (Figs. 3.3 and 3.4); both morphologies may occur within one and the same lesion [1]. The peripheral cells at the border with the adjacent fibrous stroma are columnar with nuclei usually in the apical halve of the cell body away from the basement membrane; they resemble the epithelial cells in the tooth germ that lie at the border with the dental mesenchyme (Fig. 3.5). The cells lying more centrally are fusiform to polyhedral and loosely connected to each other through cytoplasmic extensions (Fig. 3.6); they resemble the cells of the so-called stellate reticulum, another part of the tooth germ (Fig. 3.5). In the follicular type, an increase in intercellular edema may lead to cyst formation and these cysts may coalesce to form the large cavities that are responsible for the multicystic gross appearance that ameloblastomas may show (Fig. 3.7). Cyst formation may also occur in the plexiform type ameloblastoma but there, it usually is the result of stromal degeneration which means that strictly spoken, they are not cysts as they lack an epithelial lining (Fig. 3.8). At the interface between epithelium and stroma, condensation of stromal collagen may cause juxtaepithelial eosinophilic hyaline bands (Fig. 3.9). This should not be misinterpreted as dysplastic dentin as present in mixed odontogenic tumors (discussed in Chap. 5) although it seems that the possibility that ameloblastomas occasionally may show deposition of genuine dentin cannot be ruled out completely in view of some recent reports on tumors provisionally labelled as adenoid ameloblastoma with dentinoid (Fig. 3.10) [3–5]. Furthermore, there may be juxtaepithelial areas of focal myxomatous stromal degeneration that should not be confused with the myxocellular tissue that is found in mixed odontogenic tumors and forms a neoplastic tissue component of those lesions (Fig. 3.11). Mitotic figures may occur within the peripheral columnar as well as in the stellate reticulum like cells (Fig. 3.12). In the absence of concomitant cytonuclear atypia and with a normal configuration, they lack prognostic significance.

The involvement of adjacent tissues by ameloblastoma is site-dependent. In the bone marrow, the tumor infiltrates the adjacent cancellous bone (Fig. 3.13). In contrast, the cortical bone of the mandible expands through remodeling and perforation of the cortical plate is exceptional; when occurring, the periosteum still forms a barrier (Fig. 3.14) [6]. Consequently, spread into the adjacent soft tissues is highly unusual and, when observed, one should consider the possibility of an intraosseous malignant tumor, probably an ameloblastic carcinoma. In the maxilla, the tumor may grow through the covering mucosa, thus showing an ulcerating oral muosal surface (Fig. 3.15); in the mandible, the tumor will remain entirely intraosseous and submucosal (Fig. 3.16).

In addition to the two basic subtypes of ameloblastoma, follicular and plexiform, some other histologic variants can be discerned. Acanthomatous and granular cell type ameloblastoma are variants of ameloblastoma with squamous metaplasia (Fig. 3.17) and granular cells respectively (Fig. 3.18). If keratinization is abundant, leading to large cavities filled with keratin, lesions are called keratoameloblastoma (Fig. 3.19) [7]. In these tumors acantholysis may lead to a pseudopapillary lining that characterizes the variant called papilliferous keratoameloblastoma. In the basal cell (basaloid) ameloblastoma the epithelial nests lack an edematous center with cells loosely connected to each other but instead show closely packed basaloid cells, with a peripheral rim of cuboidal cells (Fig. 3.20).

Tumors with a preponderance of stroma and limited epithelium are called desmoplastic ameloblastoma. Radiologically, they may mimic fibro-osseous lesions as they have a mixed radiodense and radiolucent appearance (Fig. 3.21). They are also clinically and histologically different from the more conventional types both as this type occurs more often in the anterior parts of both maxilla and mandible and shows a dense collagenous stroma, the epithelial component being reduced to narrow, compressed strands of epithelium (Figs. 3.22 and 3.23). When these strands broaden to form larger islands, a peripheral rim of dark staining cuboidal cells and a compact center in which spindle-shaped epithelial cells assume a whorling pattern may be discerned (Fig. 3.24). Within the stromal component, active bone formation can be observed which explains the mixed radiodense radiolucent appearance at the radiographs [8].

Sometimes, ameloblastomas present themselves as a large cyst. This so-called unicystic ameloblastoma occurs at a lower mean age than the other types and may mimic a dentigerous cyst both clinically as well as radiologically because of its occasional association with an impacted tooth (Figs. 3.25 and 3.26) [9]. The lesion consists of a single cystic cavity lined by ameloblastomatous epithelium (Fig. 3.27). This epithelium may proliferate to form intraluminal nodules with an architecture similar to a plexiform ameloblastoma (Fig. 3.28) whereas downward proliferation of this epithelium may lead to infiltration of the fibrous cyst wall by ameloblastoma nests (Fig. 3.29). Sometimes, the cyst lining itself lacks any features indicative of ameloblastoma, these being confined to intramural epithelial nests [10]. Inflammatory alterations may obscure the specific histologic details to such an extent that none are left in which case the lesion may be mistaken for a radicular cyst (Figs. 3.30 and 3.31). However, as already mentioned before when discussing the differential diagnostic issues of the keratocystic odontogenic tumor, radicular cysts are usually small and confined to the periapical area of a decayed tooth whereas both keratocystic odontogenic tumor and unicystic ameloblastoma may occupy large areas of the mandibular body and are not associated with any tooth pathology. In dubious cases, immunohistochemistry may be helpful as ameloblastomas show distinct nucleo-cytoplasmic calretinin immunoreactivity that is particulary intense in the stellate reticulum-like epithelial cells and in areas of squamous metaplasia [11].