CHAPTER NINETY-THREE

Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

John W. Hellstein

Key Points
Odontogenesis is a complicated intermingling of processes with many levels of induction. There are many interactions between mesenchymal and epithelial tissues. Of particular interest is the embryology of Rathkes pouch as well as the normal distribution of dental laminae in the alveolar arches. In addition, portions of the enamel organ are the origin of most of the commonly known odontogenic cysts and tumors. The nomenclature of odontogenic and nonodontogenic cysts of the oral region is varied. Though many of these cysts are not directly covered in the Key Points, it may be beneficial for the reader to review Box 93-1 as an aid in formulating differential diagnosis lists. The keratinizing odontogenic cyst is specifically separated from the odontogenic keratocyst due to its much more innocuous presentation. The odontogenic keratocyst has also recently been renamed as keratocystic odontogenic tumor. The term primordial cyst continues to be used by some authors. However, its use often differs depending on the background of the author. Of most concern is that the term primordial cyst in many European publications is used synonymously with what it now termed the keratocystic odontogenic tumor (odontogenic keratocyst). In this chapter we will use the term odontogenic cyst of undetermined origin to describe those lesions that appear histologically identical to a dentigerous cyst or radicular cyst but are not anatomically related to any particular tooth. The odontogenic keratocyst has also been known as the parakeratinizing odontogenic keratocyst, and the WHO has recently renamed it the keratocystic odontogenic tumor. In addition, this cystic neoplasm is associated with basal cell nevus syndrome. The botryoid odontogenic cyst radiographically presents as a multilocular lesion and may recur. Histologically the lining is identical to the lateral periodontal cyst. The problem with the glandular odontogenic cyst diagnosis is that it is becoming overused due to lack of calibration and variability in its histologic definiton. For odontogenic tumors, in general readers are encouraged to always look over the general treatment considerations for each patients situation. Specifically there is some concern about the evidence-based nature of treatment recommendations related to many of the odontogenic tumors. In the case of the calcifying epithelial odontogenic tumor, older texts and even modern texts often recommend rather aggressive therapy, although there is little evidence-based literature to support initial aggressive therapy in some tumors. With the exception of the ameloblastoma, there are only sparse reports of any of the benign odontogenic tumors getting away from the surgeon even if a recurrence does happen.

Odontogenic tumors are often intricate admixes of neoplastic and nonneoplastic lesions. Even the simple odontogenic lesions have their origin traced back to odontogenesis. But odontogenesis is far from simple. By understanding odontogenesis, the readers appreciation for these lesions should be enhanced. In fact, it is the unique interaction of ectomesenchymal tissues with epithelial tissues during odontogenesis that make these cysts and tumors unique. These interactions of the mesenchyme and epithelium occur across short distances and within the confined volume of the jaws. Complications in histologic interpretation include artifacts caused by demineralization, sampling errors, separation of hard and soft tissues at the grossing bench, and general difficulties in sectioning disparate tissue types. Separation of disparate tissue at the grossing bench can make it impossible to analyze the relationship of tissues later under the microscope. Even when these background problems are not encountered, the result is often still a histopathologic hodgepodge. In the end, odontogenic lesions that

contain both epithelial and mesenchymal components are often difficult to assess histologically. A basic understanding of odontogenesis by the surgeon/clinician may help to predict behavior, enlighten the clinician on what information to give the pathologist, and guide proper treatment. Thus odontogenesis and the jaws unique status within the body create a wide set of possibilities for clinical, radiographic, and histopathologic differential diagnosis lists. It is the goal of this chapter to review odontogenesis, as well as odontogenic cysts and tumors. It is hoped by the end of this chapter that a better understanding of odontogenic cysts and tumors will lead to a more thorough appreciation of this intricate and complicated set of diseases.

Background

Odontogenesis begins within generally well-defined areas of the stomodeum, then by maturational extension the oral cavity and alveolar

1260

Part 6 n Head and Neck Surgery and Oncology

processes of the jaws. Unfortunately, simply knowing the location does not necessarily allow the clinician to always positively ascertain a lesion as being odontogenic in origin. Confounding elements include the embryologic nature of Rathkes pouch, extension of large odontogenic lesions outside the confines of the alveolar processes, and the propensity of products of odontogenesis to wander. Thus reports of sinonasal ameloblastomas and craniopharyngiomas of the sella should not be surprising and still be considered odontogenic in origin. Simply put, the only prerequisite is that all odontogenic cysts and tumors must be derived from elements of stomodeal origin. Histologically the rather unique epithelial portions of odontogenesis often remain distinct enough in cysts and tumors to allow for proper determination of origin. Unfortunately, the mesenchymal components of the dental papilla (as seen in myxomas) and cemental components (as seen in odontogenic fibromas) are impossible to definitively identify histologically as being of odontogenic origin. The only hope in identifying these as odontogenic is if they occur in association with other odontogenic epithelial elements. But generally, these mesenchymal lesions are identified as odontogenic on the basis of their location in the jaws. Though this section focuses only on odontogenesis, remember that the oral and maxillofacial region is also associated with developmental remnants of salivary glands, seromucous glands, sinonasal epithelium, nasopalatine duct epithelium, and dermal epithelia. Due to these nearby, possibly confounding embryologic tissues, the true origin of any given lesion may be cloudy at best. However, by knowing the specific location, history, and histopathologic features and being additionally armed with knowledge of odontogenesis, the proper designation for any given lesion can almost always be filtered to arrive at a relatively short differential diagnosis list. The enamel organ is generally divided into the bud stage, cap stage, and bell stage. The bud stage begins as a proliferation of the basilar cells of the stomodeum. This proliferation occurs along the area of the future alveolar mucosa apical to and separated from the vestibular mucosa. In this early stage the ectoderm of the stomodeum is lined by two to three cells. It is during the sixth week that the ectoderm in the region of the future alveolar processes begins to proliferate and form two somewhat horseshoe-shaped epithelial bands. Before being differentiated into the epithelial surfaces of the alveolar processes, each band is called a dental lamina. These dental laminae will eventually form the 20 separate proliferations necessary for the deciduous teeth. These 20 areas of proliferation are each called tooth buds. Each tooth bud then proliferates apically into the underlying ectomesenchymal tissue. Eventually at the bell stage the connection between the overlying stomodeum and the enamel organ will become separated. But the actual process of bud proliferation varies by arch, as well as by tooth type (i.e., deciduous central incisor, deciduous lateral incisor, deciduous canine, deciduous first molar and deciduous second molar). By the end of the eighth week all 20 buds have been produced. During all phases of morphodifferentiation, histodifferentiation, and apposition the features of the enamel organ and the physiologic support of the enamel organ are changing. But with apposition of the dentin and vascularization near the outer enamel epithelium the enamel organ is further defined with a fourth cell layer termed the stratum intermedium. The cells of the stratum intermedium occupy an illdefined area of flattened cells between the inner enamel epithelium and the stellate reticulum. Though the area of phenotypic change that defines the stratum intermedium must be present before enamel can be laid down, actually identifying these cells individually is extremely subjective.

epithelial root sheath. Hertwigs root sheath as it moves apically to guide root formation will leave behind epithelial rests known as rests of Malassez. These rests will reside in the region of the periodontal ligament and provide a basis for several potential odontogenic cysts and tumors. The periodontal ligament is actually a joint known as a gomphosis joint. Though the cementum cannot be distinguished except by location, the body, for instance, during orthodontic movement will resorb the bone on the lamina dura side of the periodontal ligament and not the cementum on the tooth side of the ligament. The tooth with the periodontal ligament will retain a certain amount of mobility within the joint. The reader is again referred to various texts for a more indepth coverage of odontogenesis.1-5,5a There are a number of odontogenic epithelial stages and each may provide a basis for odontogenic cysts or tumors. The four main stages considered are (1) dental lamina, (2) enamel organ, (3) reduced enamel epithelium, and (4) Hertwigs epithelial root sheath. The rests of Serres and Malassez are considered along with their respective progenitors of the dental lamina and Hertwigs root sheath. In addition, the stomodeal epithelium gives rise to Rathkes pouch, which retains odontogenic potential. Shafer and colleagues6 suggest the original basal epithelium of the stomodeum also retains potential. In the adult this basal epithelium is represented by the gingival and alveolar mucosal surfaces.6 This concept seems to be supported when peripheral ameloblastomas appear to develop directly from overlying gingival epithelium. With that said, most clinicians would consider the adult basal epithelium to be a rare source of odontogenic neoplasia. The rests of Malassez are common sources of inflammatory odontogenic cysts but retain little neoplastic potential. The rests of Serres, the enamel organ, and reduced enamel epithelium are generally considered the stages most likely to become neoplastic. All stages have the potential to form cysts but to variable degrees. Dentigerous cysts with their origin from the reduced enamel epithelium and radicular cysts from rests of Malassez make up the overwhelming majority of odontogenic cysts.

Summary

Odontogenic Cysts
When reading various sources it becomes quickly clear that what a cyst is varies by author and that the classification schemata are in disarray as well. The modified classification scheme seen in Box 93-1 is my attempt at organization. The odontogenic cyst of undetermined origin is a new, admittedly descriptive diagnosis used by some oral pathologists. Unfortunately the descriptive nature of that term will not be available to look up in other texts or journals. However, it replaces the diagnosis of primordial cyst. The need to use a descriptive term instead of primordial cyst is due to the ambiguous use of primordial cyst both as an odontogenic keratocyst (OKC) and a simple nonkeratinizing cyst that cannot be classified in relation to the tooth. The descriptive role is to provide a pigeonhole in which to place lesions that are histologically ambiguous, not directly associated with a tooth but located in the alveolus and thus presumably odontogenic in origin. Several classification schemata for odontogenic cysts and oral and maxillofacial cysts exist.7-9 The classification scheme seen here is modified from that of the World Health Organization (WHO). In 1992 WHO published the second edition of Histological Typing of Odontogenic Tumors.10 Unfortunately the most recent WHO treatise on odontogenic tumors is contained within the Pathology and Genetics of Head and Neck Tumors.11 In this change odontogenic cysts are no longer covered within the text. Box 93-1 also contains selected nonodontogenic cysts for completeness and comparison. By definition a cyst is considered a pathologic cavity at least partially lined by epithelium. To be an odontogenic cyst the epithelial lining must be derived from odontogenic epithelium. The best advice to the reader is that all classification schemata are artificial to some extent. The key is to organize them the way that is most useful to you. This modification in Box 93-1 is an attempt at self-

Classification

Root Development

In the tooth root, the dentin forms the huge majority of the root volume, which is then sheathed in a layer of cementum instead of enamel. But the odontoblasts still cannot lay down dentin without induction by epithelium derived from the enamel organ. To accomplish this feat as the reduced enamel epithelium reaches the cementoenamel junction, it becomes reduced to back-to-back inner and outer epithelial cells. This produces a collar of cells that separate from the reduced enamel epithelium. This separated collar is known as Hertwigs

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1261

Box 93-1

Classification of Odontogenic with Other Selected Maxillofacial Cysts

Odontogenic cysts Developmental cysts Dental lamina cyst (gingival cyst of newborn) Odontogenic keratocyst (called keratocystic odontogenic tumor by WHO)* Dentigerous cyst (follicular cyst) Eruption cyst Lateral periodontal cyst Botryoid odontogenic cyst Gingival cyst of adults Keratinizing odontogenic cyst Glandular odontogenic cyst Calcifying odontogenic cyst (Gorlin cyst) Odontogenic cyst of undetermined origin (replaces the term primordial cyst, which has been irretrievably confused in the literature. This new descriptor also serves as a useful designation for some lesions that do not classify well.) Inflammatory cysts Periradicular cysts Periapical cyst (apical periodontal cyst) Lateralized periradicular cyst Residual cyst Dentigerous origin Periapical origin Paradental cyst Mandibular infected buccal bifurcation cyst Inflammatory collateral cyst Nonodontogenic cysts Nasopalatine duct cyst (incisive canal cyst) Cyst of the incisive papilla Nasolabial cyst (nasoalveolar cyst) Palatal cysts of infants Epsteins pearls (midline of hard palate) Bohns nodules (scattered on palates especially at junction of hard and soft) Lymphoepithelial cysts Oral lymphoepithelial cyst Cervical lymphoepithelial cyst (branchial cleft cyst) Gastric heterotopic cyst Thyroglossal duct cyst Salivary duct cyst Maxillary antrum associated Surgical ciliated cyst Soft tissue cysts Epidermoid cyst Thymic cyst Bronchogenic cyst Trichilemmal cyst (pilar cyst) Pseudocysts Idiopathic bone cavity (e.g., traumatic bone cavity, traumatic bone cyst, simple bone cyst, hemorrhagic bone cyst) Aneurysmal bone cyst Mucus-retention phenomenon (mucous-retention cyst) Mucocele of the sinus Cystic hygroma Miscellaneous Dermoid cyst Polycystic disease of the parotid HIV-associated lymphoepithelial lesion Nonexistent/spurious cysts The following cysts are generally considered embryologically impossible or have been reclassified in previous descriptions of cysts. Globulomaxillary cyst (dismissed on the basis of embryology) Median mandibular cyst (dismissed on the basis of embryology) Median maxillary alveolar cyst (subcategory of nasopalatine duct cyst)
*Primordial cyst specifically not used synonymously.

HIV, human immunodeficiency virus; WHO, World Health Organization.

1262

Part 6 n Head and Neck Surgery and Oncology

clarification and will hopefully be useful for others in either its pure or modified form. Many odontogenic cysts are surfaced by nonkeratinized epithelium. Histologically the following nonkeratinizing cysts can look identical and cannot be separated except by clinical, historical, and/or radiographic means. These include dentigerous cyst (follicular cyst), eruption cyst, odontogenic cyst of undetermined origin, periapical cyst (apical periodontal cyst), lateralized periradicular cyst, residual cyst, and paradental cyst. These cysts make up the majority of odontogenic cysts. As a group they are known as the common odontogenic cysts. For proper diagnosis of these common odontogenic cysts the clinician must provide sufficient information for the diagnosis to be made. The reader is urged to closely note the necessary or significant features when each of these cysts is specifically discussed later in this section. The other odontogenic cysts will display histologic features to allow for the proper diagnosis, though history and communication are of course always appropriate and often essential. It is important to note that the presence of a specific type of keratin is not pathognomonic for an OKC and may be seen with other odontogenic cysts. Cyst expansion occurs because of numerous factors including accumulation of inflammatory cells, fibrin, serum, and desquamated epithelial cells. As these products enter the cystic cavity, it is the accumulation of the intraluminal products that spurs the cystic expansion of the wall.12-14 Alternatively, cyst expansion may be spurred on by the inherent mitotic activity of the cyst wall itself. If this mitotic activity is the major component of the cyst expansion, it may be better to consider the lesion a cystic neoplasm rather than a simple cyst.14-20 This debate lies at the center of how to classify the OKC, as well as the calcifying odontogenic cyst.21 In the case of the OKC, WHO has renamed it the keratocystic odontogenic tumor. Discussion of this entity is in the odontogenic cyst section. In the case of the calcifying odontogenic cyst (the tumor version), the reader is referred to more detailed articles on the epithelial odontogenic ghost cell tumor. Multilocularity may in itself be a signal that the lesional growth is mitotically or multifocally driven rather than hydraulically driven.22-25 For this reason the potentially multilocular odontogenic cysts, such as the botryoid odontogenic and glandular odontogenic cyst, may arguably have a neoplastic potential as well.22,26-30 However, in the case of the botryoid cyst the possibility of multifocality cannot be ignored. Cell regulation protein studies to determine cell inhibition and division activities may be helpful in future classifications.31,32 In addition, the ability of epithelia to break down elements of the connective tissue wall could be important.33-37 However, even simple cysts like the periradicular cyst derived from rests of Malassez must possess some mitotic activation, or growth would be impossible. Activation is thought to occur as a result of inflammatory production within the periodontal membrane.13,38 In the skin and gingiva it has been shown that inflammation leads to release of inhibitors, which then allow the renewal of mitotic activity.15 Once a solid epithelial sphere has been formed, it is thought that it eventually outgrows its vascular nourishment and the central area degenerates to form a lumen.15,16 Following the formation of the central lumen, transepithelial flow of fluid is sustained by osmotic forces. Thus hydrostatic pressure plays a role in the development of the classic unilocular appearance of most cysts. How the pressure results to produce osteoclastic resorption is less clear.17,39-41 Cysts that are derived from the more neoplastic dental lamina, or are in themselves cystic neoplasms, probably occur as a result of selfsustained or unregulated mitotic activity.42 Even in neoplastic cysts, luminal expansion may occur through degenerative effects, debris accumulation, and hydraulic and mitotic activity.43-45 The periapical cyst must be associated with a nonvital tooth. The tooth may be rendered nonvital by trauma, caries, or periodontal space extension. As such, these cysts may be seen at any age, although permanent teeth are more likely to be involved than deciduous teeth.46 They are thought to be derived from rests of Malassez.

Pathogenesis

Figure 93-1. Occlusal radiograph of large periapical cyst associated with two endodontically treated maxillary incisors.

Figure 93-2. Photomicrograph of periapical cyst showing nonkeratinizing stratified squamous epithelium with inflammation. Cholesterol slits are seen toward the left side of the luminal surface and appear as empty white clefts.

Radiographic Features Periapical cysts present as a unilocular radiolucency at the apical portion of the tooth. Though well defined, the border varies from corticated to sclerotic to merely well defined. Variations depend on the amount of inflammation present. Long-standing, neglected lesions can get quite large, though most are less than 1 cm in diameter (Fig. 93-1). Microscopic Features This is the classic inflamed common odontogenic cyst and as such the luminal lining will consist of nonkeratinized stratified squamous epithelium. This is an inflammatory cyst and inflammation is invariably present if sufficient sampling is performed (Fig. 93-2). Rests of Malassez are possible in the connective tissue. However, odontogenic rests are rarely seen in the cyst wall even though these rests are thought to be the source of the epithelial proliferation. Cholesterol slits, foreign body giant cells, and hemosiderin deposits are common findings. As in all common odontogenic cysts, squamous odontogenic tumor-like proliferations may be seen in long-standing lesions. These epithelial islands will be cytopathologically benign without evidence of dysplasia. If squamous odontogenic cystlike proliferations are noted, they should essentially be ignored and are of no prognostic significance. In endodontically treated teeth, foreign bodies secondary to endodontic therapy are common.47 Bacterial colonies may also be seen in these cysts. Though actinomycetes colonies may portend a tendency for being slow

Periapical Cyst (Radicular Cyst, Periradicular Cyst)

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1263

Figure 93-3. Clinical photograph of cyst seen in Figure 93-1 before enucleation.

Figure 93-4. Intraoperative photograph of an inflammatory collateral cyst. Tooth is vital with periodontal pocket leading to intrabony cystic area.

to resolve, their presence should not result in a diagnosis of osteomyelitis. Such colonies are more commonly an incidental rather than a significant finding. Thus, for multiple reasons, the proper diagnosis of periapical cyst requires radiographic or clinical corroboration. Treatment This cyst is treated with simple enucleation (Fig. 93-3). Enucleation is often accomplished at the time of tooth extraction. Uncounted numbers of these cysts are probably adequately resolved with endodontic therapy. If a radiolucency persists longer than 6 months following endodontic therapy, enucleation and histopathologic review are necessary.48-50

Lateralized Radicular Cyst (Lateral Radicular Cyst, Lateral Periapical Cyst)

This cyst is simply a variant of the periapical cyst. It is associated with a nonvital tooth, but instead of being at the apex of the tooth the cyst is located lateral to the tooth root(s). This happens because the root canal system of teeth sometimes has exits on the lateral aspect of the root, not just at the apex. Therefore if the path of least resistance is out one of these lateral canals the lesion will be present laterally. Otherwise, the clinical, microscopic, radiographic, and histologic features are identical to the periapical cyst.

Residual Cyst

The majority of these cysts will be the result of leaving a periapical cyst behind following tooth extraction. All of these cysts are inflammatory cysts. Occasionally an inflamed dentigerous cyst is incompletely removed and could also be the source of a residual cyst. The clinical, microscopic, radiographic, and histologic features are identical to the periapical cyst.48,49,51,52

Figure 93-5. Radiograph of inflammatory collateral cyst.

Inflammatory Collateral Cyst

This may or may not be considered by some to be a true cyst. However, because it is an occasionally used diagnosis, a quick summary is included here. This lesion is associated with periodontal disease of a vital tooth. Uncommonly, a deep intrabony periodontal pocket may be sufficiently isolated to allow for hydraulic expansion of the bone (Fig. 93-4). As such, radiographically there will be a radiolucent periradicular lesion (Fig. 93-5). There will also be a periodontal pocket associated with that radiolucency. This diagnosis should be limited to those cases where the clinician indicates the diagnosis as the most likely choice. Otherwise, the clinical, microscopic, radiographic, and histologic features are identical to the periapical cyst.53

Dentigerous Cyst (Follicular Cyst)

The dentigerous cyst by definition must be associated with the crown of an unerupted tooth, developing tooth, or odontoma. The eruption

cyst is essentially a subtype of dentigerous cyst that is confined just by the overlying alveolar mucosa. Dentigerous cysts form when fluid accumulates between reduced enamel epithelium and tooth crown.14 As alluded to earlier, the accumulation of fluid may be partially or largely surrounded by connective tissue and epithelium.54,55 Because the third molars and maxillary canines are the teeth most frequently impacted, they are also the most likely to be associated with dentigerous cysts. However, any impacted tooth has an increased risk. There also may be inherent differences in impacted tooth development and how the reduced enamel epithelium is transformed/resorbed.56 They are generally found in the teenage years and early adulthood.57 However, the longer a tooth is impacted, the greater the chance a dentigerous cyst will develop.58

1264

Part 6 n Head and Neck Surgery and Oncology

Figure 93-6. Radiograph of large dentigerous cyst associated with molar crown.

Figure 93-7. Clinical photograph of device used for cyst decompression. Note two holes to allow for proper irrigation (arrows). The device is constructed from acrylic resin with a central waist and blunderbuss ends. To keep it in place, nonresorbable sutures may be necessary for 2 to 3 weeks.

Radiographic Features A dentigerous cyst presents as a unilocular radiolucency, which is associated with an unerupted tooth (Fig. 93-6). Dentigerous cysts may also involve odontomas that, by nature, also have tooth crowns. The radiolucency is generally well demarcated and well corticated. The border may become sclerotic or display rarifying osteitis if secondary infection is present. Even large cysts that have pushed the associated tooth considerable distances will display evidence of origin from the cementoenamel junction if the film angle is adequate. In large lesions the origin from the cementoenamel junction is best visualized as an area of cortication at the cementoenamel junction. There is considerable overlap between the appearance of small dentigerous cysts and hyperplastic follicles.56 Microscopic Features The specimen will present primarily as variably dense fibrocollagenous connective tissue with some areas being loose and myxomatous. Odontogenic epithelial rests are usually scattered within the connective tissue and are most common near the epithelial lining. The luminal lining consists of nonkeratinized stratified squamous epithelium. The presence of mucous prosoplasia within the lumen is not uncommon. Care should be taken to not overinterpret the mucus prosoplasia. Cholesterol slits and their associated multinucleated giant cells may be present in inflamed cysts and are generally associated with the connective tissue wall.47 As mentioned earlier, the lumen may be partially or mostly lined by connective tissue.14 If present in the specimen, crevicular epithelium may make microscopic separation of an inflamed dentigerous cyst from pericoronitis impossible. Thus proper diagnosis requires radiographic or clinical corroboration. Neoplastic Potential Dentigerous cysts appear to retain the ability to transform into true neoplasms. One study reported that 17% of ameloblastomas were associated with an existing dentigerous cyst.59 This figure varies by study, however.60-62 Both squamous cell carcinomas and mucoepidermoid carcinomas have been reported.63-67 Treatment Dentigerous cysts are usually easily enucleated at the time of tooth extraction. In large lesions decompression with subsequent enucleation may be appropriate (Fig. 93-7).

Figure 93-8. Clinical photograph of maxillary eruption cyst found incidentally in an infant.

or permanent teeth, but the majority of lesions are seen in the first decade.68 The lesion will present as a soft tissue swelling of the alveolar ridge overlying an area of age-appropriate tooth development. Some eruption cysts will have a slightly blue hue color, though the normal coral pink color of the surrounding mucosa is common (Fig. 93-8). Unlike dentigerous cysts, it is not uncommon for an eruption cyst to be associated with deciduous teeth. Eruption cysts may be seen in newborns with an incidence of 2 per 1000 births reported.69 Clinical follow-up may also serve to confirm the diagnosis because the tooth will erupt within several weeks to months through the cystic expansion.70-74 Treatment The eruption cyst almost always resolves without intervention. In uncommon cases eruption of the underlying tooth may be impeded or delayed. In such cases a deroofing will allow eruption.

Paradental Cyst

Eruption Cyst

The eruption cyst is a form of dentigerous cyst that is found in the soft tissue overlying an erupting tooth. Because by definition it must be associated with an erupting tooth, eruption cysts occur only during the ages of tooth development.7 They may be seen with erupting deciduous

The paradental cyst is considered by some to be a variant of the dentigerous cyst. This is because the various forms of paradental cyst all originate from the cementoenamel junction just like the dentigerous cyst. However, the paradental cysts are almost uniformly inflamed, so they are generally classified as inflammatory cysts rather than as developmental cysts. Paradental cysts occur on the buccal or distal aspect of

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1265

an erupted mandibular molar. Though the mesial aspect of a mandibular tooth may rarely be involved, there have been no reported occurrences to the lingual. Craig75 reported the occasional presence of developmental enamel projections near the furcation of some teeth. This is particularly true of the subcomponent of paradental cysts known as infected buccal bifurcation cysts. How big a role these projections play in pathogenesis remains debatable.76-81 In one series the paradental cyst accounted for 3% of all odontogenic cysts.82 Radiographic Features The lesion will present as a well-defined radiolucency associated with but not surrounding the coronal area of a partially erupted tooth.81 It is with great regret that another diagnosis is added to the list of odontogenic cysts, but there appears to be no good alternative. On occasion the clinician and pathologist may come upon a lesion that is not classifiable by histologic, radiographic, or clinical features. As mentioned earlier, several odontogenic cysts have identical microscopic features. Odontogenic cysts with identical or potentially identical histologic features are referred to as the common odontogenic cysts. These common cysts are separated on the basis of clinical features alone. The problem in diagnosis comes when a cyst is not associated with the crown of a tooth, residually or with the root of a nonvital tooth. Additionally, the cyst is not consistent with a fissural cyst but is at least partially located in the alveolar process. Historically, any cyst that occurred in an area where a tooth should have developed, or where supernumerary teeth could occur, were originally called primordial cysts.83 This term was used to allude to development from the tooth primordium. Unfortunately, this was proposed in 1945 before delineation of the features defining the OKC and a large percentage of these primordial cysts had features of what would now be diagnosed as an OKC. When the OKC was defined in the 1950s, some pathologists had already recognized those histologic features in what they termed primordial cysts and thus they began to use the term interchangeably with OKCs. International journals, especially, came to use the term primordial cyst as a synonym of the OKC.45,84 Americans often avoided the term primordial or left the moniker of primordial cyst for those lesions without features of a keratocyst. The term primordial cyst is avoided to eliminate any confusion between the histopathologist and the clinician. This is intended to ensure that aggressive treatment of an OKC is not performed for this innocuous lesion.

Odontogenic Cyst of Undetermined Origin

Figure 93-9. Radiograph of an odontogenic cyst of undetermined origin.

Definition of the Odontogenic Cyst of Undetermined Origin

An odontogenic cyst of undetermined origin is a unilocular radiolucent cyst of the jaws with histologic features of common odontogenic cysts but lacking the clinical, histologic, and radiographic features of any defined common odontogenic cyst (Fig. 93-9). These cysts are thought to be derived from the dental lamina and are thus thought to retain some limited neoplastic growth potential. This limited neoplastic potential is best displayed by the associated lesion known as a botryoid odontogenic cyst. Lateral periodontal cysts are located on the lateral surface of a vital tooth.85,86 This assumes that the tooth has not been rendered nonvital by dental caries or trauma unrelated to cyst formation. The most common location is the mandibular premolar/canine area. If present in the maxilla, the lateral incisor area is the most common location. However, the lateral periodontal cyst may be seen in any area of the alveolar processes. This cyst is seen in the interproximal area between tooth roots and is usually an incidental radiographic finding.87,88 Demographically the cyst is most common in males by a 2 : 1 ratio with a peak incidence in the fifth and sixth decades.89 The gingival cyst of the adult and the botryoid odontogenic cysts are essentially subtypes of lateral periodontal cysts. Other cysts, especially the OKC, odontogenic cyst of undetermined origin, and the lateralized periapical cyst, also present interproximally. Histopathologic features and tooth vitality are important diagnostic considerations to

Figure 93-10. Photomicrograph of generally thin cyst lining typical of the lateral periodontal cyst.

Lateral Periodontal Cyst

separate these lesions. All of these lesions can be separated histologically and the lateralized periradicular cyst will be associated with a nonvital tooth. Radiographic Features The lesion presents as a unilocular radiolucency of the alveolus that is usually well corticated. Larger lesions may result in diverged roots.90 Multilocular lesions are a special subset and are classified as botryoid odontogenic cysts (see Botryoid Odontogenic Cyst later).27 Microscopic Features The cyst lining is composed of nonkeratinized simple to stratified squamous epithelium. The lining is most notable for being only a few cells in thickness (Fig. 93-10). Intermixed within this otherwise thin epithelial lining are nodular epithelial thickenings or plaques. The plaques may display somewhat whorled epithelial cell aggregates. The central cells in the aggregate may display cytoplasmic clearing. The clear

1266

Part 6 n Head and Neck Surgery and Oncology

cells contain glycogen, which can be digested with diastase. Scattered mucous cells may be seen in some lesions but should not be a dominant feature.90,91 The diagnosis of lateral periodontal cyst must be reserved for lesions displaying the thin epithelium described earlier. The plaquelike thickenings are helpful microscopic features but are not always found. The connective tissue wall may contain dental lamina rests, but they are not required for diagnosis. Treatment These cysts are treated with simple enucleation, though the surgeon is reminded to look for intraoperative multilocularity, which may not have been evident radiographically. If multilocularity is present, the lesion is probably a botryoid odontogenic cyst. In such cases light curettage of the surrounding bone wall is advised. Recurrence of the simple lateral periodontal cyst is not a problem and even the recurrences of botryoid cysts are usually easy to manage.

Botryoid Odontogenic Cyst

The botryoid odontogenic cyst will usually present as a multilocular lesion and is a special variant of the lateral periodontal cyst. Botryoid refers to the fact that these lesions may appear like grapelike clusters, both histologically and usually radiographically as well.23,25,27 Radiographic Features Radiographically the botryoid odontogenic cyst presents in the same preferred alveolar process locations as the lateral periodontal cyst. Small locules may not be seen on radiographs.23 Treatment Like the lateral periodontal cyst, treatment consists of enucleation with bony curettage. The multilocular nature may make this difficult, especially if teeth are to be spared. With full enucleation, light bone curettage recurrence should be uncommon. The slow growth of these lesions suggests that a 10-year radiographics is reasonable, though the small sample size makes this a suggestion at best.

Figure 93-11. Clinical photograph of possible gingival cyst of the new born. Light color favors dental lamina cyst rather than eruption cyst. Cyst spontaneously resolved.

differentiated by location. The gingival cyst of the newborn is a soft tissue cyst and does not have an intrabony component (Fig. 93-11).97 Microscopic Features These cysts should generally never appear for pathologic review. Treatment These cysts almost always spontaneously rupture and require no therapy whatsoever. Occasionally a cyst will be large enough to interfere with nursing or persist to 6 or more months of age. In these rare cases, simple enucleation or even deroofing is sufficient.

Gingival Cyst of the Adult

Clinical Features This lesion is essentially the soft tissue equivalent of the lateral periodontal cyst. As with the lateral periodontal cyst, it derives from dental lamina or rests of Serres.92-94 These lesions generally present as an asymptomatic bluish nodule on the facial aspect of the gingiva. The sessile elevation will be centered in the attached gingiva, though extension below the mucogingival line is possible. Unlike the lateral periodontal cyst, there may be a slightly increased incidence in women.95 The mandibular gingiva is most commonly involved and the peak incidence occurs in the fifth and sixth decades.9,96 Other odontogenic cysts may also occur in the gingiva. Histologically distinctive odontogenic cysts that are appropriately diagnosed histopathologically should not be descriptively called gingival cysts. The possibility of some cysts of the gingivae arising from traumatically implanted surface epithelium does exist. Whether it is best to call these histologically different cysts epithelial inclusion cysts is debatable.95 The term gingival cyst of the adult must be reserved for those lesions with histologically distinct microscopic criteria. Radiographic Features The lesion may sometimes display superficial cupping of the cortical bone. This cupping is usually only detected intraoperatively.

Gingival Cyst of the Newborn (Dental Lamina Cyst, Alveolar Cyst of the Newborn)

These cysts occur on the alveolar ridge of newborns. They are generally only a few millimeters in diameter and seen only in the first few months of life. Though studies are appropriately devoid of histologic sampling data, some clinical reports estimate these cysts occur in up to 50% of all newborns. The cysts are sessile and vary from normal in color to yellow or white. Similar-appearing inclusion cysts of the palatal midline (Epsteins pearls) or at the junction of the hard and soft palates (Bohns nodules) are

Recognition of the keratinizing odontogenic cyst is a rather recent phenomenon. When the OKC was first defined, the definition did not separate these lesions. Over time several reviewers noted and separated keratinizing cysts that did not seem to otherwise conform with the microscopic criteria of the OKC.98-100 The most notable difference in these cysts was the presence of orthokeratin rather than parakeratin, though other features such as lack of tombstoning, corrugation, and hyperchromatism are more important criteria. Wright101 was the first to formally separate this group of cysts and proposed the name of OKC, orthokeratinizing variant. He noted the different histopathologic features and ably reported the lack of recurrences associated with these orthokeratinized cysts. However, the nomenclature of including the term keratocyst has created quite a bit of confusion, at least anecdotally. Historically, older texts and articles described keratinization of various odontogenic cysts and recognized the difference of these cysts from OKCs.47,100 The designation as orthokeratinized OKC (OKC, orthokeratinized variant) has evolved since first being described. Current nomenclature has evolved to avoid confusion with the standard OKC. It is also worth noting that some OKCs can contain orthokeratin, and the original series of orthokeratinizing OKCs described by Wright included 7 of 60 cysts with parakeratin.101 Thus classification based solely on the type of keratin alone is unwise. The separation of the keratinizing odontogenic cyst is clinically important because the reported recurrence rate of the keratinizing odontogenic cyst is only 2%. The peak incidence of keratinizing odontogenic cysts is in the third, fourth, and fifth decades, with about three fourths of them being in a dentigerous cyst relationship. Other locations are possible, in various relationships to the teeth. Most cysts are asymptomatic, though pain and swelling was reported respectively in 22% and 13% of cases.98,99 The keratinizing odontogenic cyst is not associated with basal cell nevus syndrome (Gorlin-Goltz syndrome).

Keratinizing Odontogenic Cyst (Orthokeratinizing Odontogenic Cyst, Orthokeratinizing Odontogenic Keratocyst)

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1267

Figure 93-12. Radiograph associated with crown of impacted mandibular canine. Note that the tooth is the left canine, which has translocated across the arch.

Radiographic Features The cyst presents as a well-defined unilocular radiolucency with the border generally being well corticated. If it is in a dentigerous cyst position, a cyst may be large (Fig. 93-12). Microscopic Features The epithelial lining will most often be thin with keratinization. However, the thickness will be somewhat variable. Keratin production varies and may only occur on a portion of the cyst wall. Orthokeratin is characteristic but not pathognomonic.102 Most notable are the features that are not present. The features defining an OKC are absent.

Figure 93-13. Photomicrograph showing mucus cells and spherical aggregate of glandular cells. Note: A single focus of such changes is not sufficient to make the diagnosis of glandular odontogenic cyst.

Odontogenic Keratocyst (Parakeratinizing Odontogenic Keratocyst, Keratocystic Odontogenic Tumor)

The OKC remains an enigma for the clinician and researcher, although knowledge gains in recent years have allowed for an improved understanding of this interesting lesion. The lesion was first described by Philipsen in 1956, but even 5 decades later the debate continues over the pathogenesis, behavior, treatment, and classification of this cystic neoplasm.18-20 One major dilemma is whether to classify it as a cyst or a neoplasm. The current World Health Organization (WHO) nomenclature stresses the neoplastic nature and uses the term keratocystic odontogenic tumor. Soft tissue extension, extension into adjacent bones, and expansion with associated bony destruction have been reported. These reports have prompted clinicians to question what the most appropriate method of treatment really is. Scharfferter and colleagues110 documented increased mitotic activity within the epithelial lining of the OKC, which seems to support its neoplastic nature. OKCs occur over a large age range. Lesions are often found during and slightly after odontogenesis of the permanent teeth. Peak incidence is in the second and third decades but may occur at any age. The mandible is more often involved than the maxilla, but treatment of maxillary lesions is often more problematic. OKCs are most common in the mandibular third molar area, but any area of the jaw may be involved. Patients are often symptomatic with swelling, pain, trismus, sensory deficits, and infection being the most common complaints. However, the lesion may also present as an incidental radiographic finding. Of particular interest to the clinician is the biologic behavior of the OKC. Recurrence rates of up to 62.5% have been reported with enucleation alone. However, modern reports have a much lower recurrence rate when enucleation and careful curettage are performed. Most modern recurrence rates are less than 10%.111,112 Reasons to explain the recurrence rate include daughter or satellite cyst formation113; incomplete removal of the epithelial lining, leaving satellite cysts left behind; collagenase activity of the cyst114; dental lamina rests left in the cyst wall or overlying mucosa; prostaglandin-induced bone resorption115; and increased mitotic activity. A handful of articles have demonstrated that the OKC can proliferate within muscle, and death from intracranial extension of mandibular OKCs has been reported by Jackson and colleagues.84,116,117 Though these case reports should be remembered, the need to aggressively treat all OKCs should be resisted. Radiographic Features OKCs may be unilocular or multilocular, multiple, or single. OKCs with calcifications within a cyst wall have been reported, but calcification is rare and OKCs are considered radiolucent lesions. OKCs are highly variable in size (Fig. 93-14). They can appear pericoronally,

Glandular Odontogenic Cyst (Sialo-odontogenic Cyst)

Clinical Features Controversy encompasses this lesion and undoubtedly further delineation of features will evolve. The glandular odontogenic cyst is usually asymptomatic and involves the mandible more often than the maxilla.29,103 Large cysts may be destructive and expansile.104,105 The glandular odontogenic cyst involves adults and its pathogenesis is not yet understood.106 This cyst may be either multilocular or unilocular. The cyst is generally well defined and often well corticated. Radiographic Features The lesion is radiolucent and may be unilocular, but it is more commonly multilocular. The radiographic margins are well defined and usually display a sclerotic rim.107 Microscopic Features This cyst is lined by cuboidal epithelium of varying thickness, which may display cilia. Unfortunately, separating this particular microscopic feature from normal (and insignificant) mucus prosoplasia is sometimes difficult. The following features are more important in establishing the diagnosis. The cyst lining will be mucicarmine positive. The mucin detected by mucicarmine collects in small pools. Characteristically there are cuboidal cells near the surface, which give a slightly papillary appearance to the lumen.103 The epithelium will also contain spheroid aggregates of cells.108,109 The presence of mucous cells in other odontogenic cysts is not diagnostic for this lesion. This lesion, in this authors opinion, is overcalled and second opinion is often necessary. Standard common odontogenic cysts with mucus prosoplasia are often upgraded to glandular odontogenic cysts (Fig. 93-13). Glandular odontogenic cysts may be upgraded to central mucoepidermoid carcinoma. Great care to properly designate these lesions is necessary to ensure proper patient care. Treatment Recurrence after enucleation has been reported.103 As in any multilocular lesion, nucleation and curettage of bone is recommended. Few cases are available to draw further treatment conclusions, but the overall prognosis is good.30 Suggestions to treat this cyst aggressively appear to be misguided.

1268

Part 6 n Head and Neck Surgery and Oncology

Figure 93-14. Radiograph of odontogenic keratocyst with bowing of inferior border and scalloping.

periradicularly, interradicularly, apically, and even peripherally. In summary, OKCs may occur in all areas of odontogenesis and they may extend significant distances.97 The borders are well defined and often corticated.98,118 Patients involved with Gorlin syndrome are more likely to present with metachronous or synchronous cysts. CT scans may be helpful in assessing large lesions and CTs are often essential in assessing maxillary lesions.119-121 Microscopic Features The OKC has a specific microscopic appearance and the mere presence of a keratin lining or keratin within the cyst lumen is not sufficient to assure a diagnosis of OKC. The other features unique to the OKC must also be seen. The stratified squamous epithelium is generally 4 to 10 cells thick. The basal cell nuclei are particularly hyperchromatic, but even the parabasalar cells are more hyperchromatic than the spinous cells seen in other odontogenic cysts. The basal layer consists of cuboidal to columnar cells with a palisaded or tombstone appearance. Corrugated surface changes are often seen at the surface. Of perhaps least diagnostic help is the finding that OKCs are surfaced by parakeratinizing stratified squamous epithelium. Again, parakeratin is not pathognomonic for an OKC. Treatment A handful of reports with significant complications have led some clinicians to perform aggressive surgical procedures on all lesions. Debate persists about how to best manage OKC lesions in general. Treatment should center on decreasing the recurrence rate to a rate expected of the modern era and one that reduces patient morbidity. The reader is referred to other articles. After reading many treatises, the following is my opinion.111,112,122-130 Close radiographic follow-up is perhaps the most important modality to prevent complications secondary to recurrence. Recurrences, which often occur in the first 5 years, can take many years to present. Recently at this institution, my colleagues and I saw a recurrence 40 years after initial treatment, though the possibility of a new occurrence could not be eliminated. Establishing a diagnosis is important. Adequate material must be sent to be histologically diagnosed. Common problems are that the inner layer of keratin within the lumen is sampled and the diagnostic lining and wall are not submitted. Additionally, the diagnostic histologic features can be lost when inflammation is present. If the patient has more than one cyst, the possibility of basal cell nevus syndrome is elevated. All cysts should still be examined histopathologically to confirm diagnosis. Clinical work-up to assess for syndrome is always prudent when multiple concurrent or sequential

OKCs are diagnosed. Even when OKCs are in teenagers or younger patients are diagnosed with a single lesion, at least a cursory family history and gross clinical assessment for the syndrome should be performed. Some investigators have claimed good success with decompression and subsequent enucleation, while others advocate enucleation, excision of overlying mucosa, peripheral osteotomy, and chemical curettage.125,129 The use of Carnoys solution is controversial. Carnoy first reported use of his fixative for the study of nematodes in 1887.131 His goal was to fix the tissue and preserve nuclear detail for microscopic examination. However, fixation of the tissue intraoperatively for future microscopic exam is not really the effect that surgeons desire. Surgeons desire the chemical cauterization effect that the solution produces. Regardless of the technique, the cyst lining must be entirely removed including satellite cysts and dental lamina rests. Thus careful enucleation is followed by some bone removal. Generally this is removal of daughter cysts and rests accomplished through curettage, peripheral ostectomy with rotary bur, or excision of one anatomic boundary such as periosteum (when bone penetration has occurred). Recurrent OKCs may need to be treated more aggressively than primary lesions, but in syndrome patients recurrences should be considered new occurrences rather than recurrences. Large lesions may leave no other option than resection. However, one should consider decompression to shrink the lesion, followed by enucleation and curettage. In this manner a discontinuity defect or damage to vital structures is reduced or eliminated. If cortical perforation is encountered, frozen sections to assess margins may be necessary. Regardless, patients must be followed on a regular basis for many years following treatment of an OKC. As with most odontogenic lesions, surgery should be dictated by the destruction already caused by the lesion at hand, rather than simply on the histologic diagnosis.

This complex syndrome is called by many names, and the nomenclature often depends on what portions of the syndrome (e.g., bifid ribs, OKC) are present. In the Gorlin and colleagues132-134 description, no fewer than 37 anomalies have been associated with this syndrome. The reader is referred to the original sources. OKCs are often the first diagnosis of the syndrome to present in childhood and often aid in establishing a diagnosis. This is especially true in cases in which there are new mutations with no prior familial history.135 Up to 40% of cases may be new mutations, though genetic testing is advancing and there may be large variations in expression in this autosomal dominant disease.134 One patients first cyst occurred in the seventh decade. For this reason the syndrome should not be ruled out even in a middle-aged patient, and family history and phenotype may help in all age groups. Treatment The key to management of these patients is to at least phenotypically evaluate any patient that has an OKC for the syndrome. The assessment may be as simple as screening the patient for clinical evidence of any anomalies. In syndromic patients, recurrences should be presumed new occurrences rather than recurrences. Decompression is highly desirable in large lesions, and teeth should generally be saved rather than extracted if possible. Undoubtedly some teeth will need to be removed for access, but canines, incisors, and first molars should be heavily favored for retention. Each case is highly variable. As a medical advisor for this syndromes support group I invite all providers to contact www.bccns.org for information. The calcifying odontogenic cyst (COC) is an unusual odontogenic lesion. As with the OKC, experts debate whether to classify the COC as a cyst or neoplasm. In this chapter the primarily cystic lesion with ghost cells is considered first, and the more solid epithelial odontogenic ghost cell tumor is considered later. The cyst was described by Gorlin and colleagues136,137 in 1962. It is worthy of delineation because of its unusual clinical and histopathologic features. The COC occurs both

Basal Cell Nevus Syndrome (Gorlin Syndrome, Gorlin-Goltz Syndrome, Nevoid Basal Cell Carcinoma Syndrome)

Calcifying Odontogenic Cyst (Gorlin Cyst)

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1269

Treatment Treatment of the COC is simple enucleation of unilocular lesions. As in any multilocular lesion, enucleation with bony curettage is adequate therapy for the central lesions. The peripheral lesions require simple excision.143 Recurrence is not expected, though radiographic follow-up is prudent.

Conclusion, Odontogenic Cysts

This chapter does not address every cyst that can affect the jaws. However, the intent by the author was to provide an overview of odontogenic cysts from the standpoint of behavior. Most cysts involving the jaws can be treated adequately with enucleation with or without curettage. In general multilocular cyst or cysts with scalloped borders need enucleation with bony curettage. Unilocular cysts can be simply enucleated. However, some cysts such as the OKC or certain variants of the calcifying odontogenic cyst, due to their neoplastic nature, may require additional surgical treatment, with enucleation and bony curettage advisable in all lesions. As stressed repeatedly, the treatment is often dictated more by the behavior (destruction the lesion has already caused) than by the histologic diagnosis.

Figure 93-15. Photomicrograph showing ghost cells, odontogenic epithelium, and stellate reticulum-like areas.

within the bone and peripherally in the gingiva. COCs are often associated with odontomas or active products of odontogenesis.138 The separation of the cystic lesions from the solid lesions is appropriate. The solid/neoplastic version is considered briefly in the odontogenic tumor section under epithelial odontogenic ghost cell tumor.139 The occurrence of the COC compared with the epithelial odontogenic ghost cell tumor may approach 40 : 1. Subclassification of the cysts is more of a histologic exercise than of prognostic or therapeutic importance. The reader is directed to articles by Praetorius and colleagues and Hong and colleagues for subclassification schemata.140,141 The origin of the COC is probably the early dental lamina. This may be best supported by the fact that craniopharyngiomas of the pituitary region often mimic the COC. COCs occur over a large age range. Though the mean age at occurrence is in the fourth decade, the peak incidence is in the second and third decades. Lesions in young adults are often associated with odontomas. The anterior portion of the jaws is more commonly involved than posterior regions, though any area can be involved. There is essentially equal distribution between females and males when all types are considered. There may be a slight maxillary predominance over the mandible.139 Peripheral COCs will be centered in the attached gingiva. Radiographic Features The radiographic appearance is highly variable. As with the OKC, it may be either unilocular or multilocular, though unilocular lesions are more common. This is one of the odontogenic lesions that is classically considered to be mixed radiolucent radiopaque, though most lesions are purely radiolucent in the absence of an associated odontoma. If mineralization occurs in COCs without an odontoma, the radiopacities are often peripherally located. This appearance has been compared to snowdrifting.142 Microscopic Features Ghost cells are the classic cells seen in the COC. Ghost cells are not pathognomonic of COCs. In fact, ghost cells may be seen with other lesions such as odontomas, ameloblastic fibro-odontomas, and ameloblastomas. Of more significance is the presence of odontogenic epithelium with hyperchromic nuclei and somewhat of a palisaded basilar layer (Fig. 93-15). The thickness of the cyst wall is fairly thin and generally less than 10 cells thick. However, the thickness varies along the luminal wall and plexiform connections are often present, which creates a multicystic appearance in more complicated cysts.

Malignant transformation of odontogenic cysts is fortunately a rare occurrence but nonetheless occurs.144-146 Many malignant transformations are considered to arise from residual cysts and occur in an edentulous area.147,148 Transformation from an associated dentigerous cyst is seen in 25% of the reported cases.146 Some OKCs have shown dysplastic features with few actually undergoing malignant transformation.149,150 In summary, any cyst can undergo malignant transformation but such lesions are rare. Malignant lesions are likely to present with pain and swelling, but dysthesia is a foreboding symptom. Gardner reviewed the literature from 1889 to 1967 and found 25 acceptable examples of carcinoma arising from an odontogenic cyst.151 A MEDLINE search for this chapter yields more than 100 additional examples. Central mucoepidermoid carcinomas are thought to arise directly from prosoplastic cells of odontogenic cyst linings.67,152-154 However, almost all types of salivary gland malignancy have been reported centrally in the jaw and the possibility of entrapped salivary tissue cannot be totally excluded. Bruner and Batsakis153,155-157 reviewed a total of 66 reported cases of central mucoepidermoid carcinomas of the jaws, which indicates they may be more commonly reported than central squamous cell carcinoma malignancies. Elzay156 offered a classification for primary intraosseous carcinomas of the jaw in 1982. A scheme of classification is offered in Box 93-2 with modifications from that of Elzay to allow for salivary malignancies (especially mucoepidermoid carcinomas), origin from odontogenic tumors (other than ameloblastoma), and inclusion of sarcomas. Verifying carcinomas arising de novo is difficult, but de novo cancers may be assumed if confined to intra-alveolar bone without a soft tissue component. Cysts appear to be a more common site of origin than odontogenic tumors. But nearly all odontogenic tumors have been reported to have malignant counterparts. The age at occurrence is in the sixth or seventh decade with some reports of a 2 : 1 male predominance, but full-ranging reviews are lacking.157 And even if such reviews were available for all lesions seen in Box 93-2, their wildly variable characters would most likely be as appropriate as comparing apples with oranges.

Malignant Odontogenic Tumors and Malignancies Arising in Odontogenic Cysts or Tumors

Microscopic Features Treatment

All malignant lesions are based on histopathologic criteria. Significant treatment and prognostic differences exist between central squamous cell lesions and central mucoepidermoid lesions.158 Treatment is based on size, histologic type, and histologic grade.

1270

Part 6 n Head and Neck Surgery and Oncology

Box 93-2

Classification of Malignant Odontogenic Tumors with Other Selected Malignancies

Type I Arising ex odontogenic cyst a. Squamous cell carcinoma b. Mucoepidermoid carcinoma Type II Odontogenic carcinomas a. Ameloblastoma derived 1) Malignant ameloblastoma (normal ameloblastoma found as a metastatic lesion) 2) Ameloblastic carcinoma (cytologically malignant) b. Clear cell odontogenic carcinoma c. Malignant epithelial odontogenic ghost cell tumor d. Malignant calcifying epithelial odontogenic tumor Type III Arising de novo (presumed from odontogenic epithelium) a. Squamous cell carcinoma 1) Nonkeratinizing 2) Keratinizing b. Mucoepidermoid carcinoma 1) Low-grade 2) High-grade c. Most salivary gland malignancies have been reported centrally in the jaws Type IV Sarcomas of possible odontogenic origin or with mesenchymal component a. Ameloblastic fibrosarcoma b. Fibrosarcoma c. Myoepithelial carcinoma

Box 93-3

Classification of Odontogenic Tumors

Epithelial odontogenic neoplasms Ameloblastoma Adenomatoid odontogenic tumorCase 2 Calcifying epithelial odontogenic tumor Squamous odontogenic tumor Keratocystic odontogenic tumor Epithelial odontogenic ghost cell tumor Mixed epithelial and mesenchymal odontogenic neoplasms Ameloblastic fibroma Ameloblastic fibrosarcoma Ameloblastic fibro-odontoma Odontoma Complex odontoma Compound odontoma Odontoameloblastoma Mesenchymal odontogenic neoplasms Odontogenic myxoma Cementoblastoma Ossifying fibroma

Odontogenic Tumors

The odontogenic tumors are a heterogeneous group of tumors that are generally separated in classification schemes by what components of odontogenesis are present within the tumor. Box 93-3 shows the classifications used in this chapter. When reviewing the treatment of these tumors, multiple considerations must be accounted for. When many

articles are reviewed it becomes clear that there is a great desire for a cookie cutter type of recipe approach for every lesion based on diagnosis alone. Unfortunately, this just is not a realistic approach and in this authors opinion has resulted in gross overtreatment in a number of patients. As with the odontogenic cysts, the presence of scalloping and particularly multilocularity makes curettage following enucleation necessary. Although scalloping and multilocularity may be seen on planar films, intraoperatively the surgeon is in an ideal position to assess for these features in three dimensions. If scalloping or multiple locules are noted intraoperatively, curettage is appropriate at the time of biopsy to avoid having to reoperate. The maxillofacial community has, in general, been a poor steward in defining criteria, measuring outcomes, reporting postoperative morbidities, and analyzing methods in relation to benign odontogenic tumors. This poor stewardship is true in both arches but is especially problematic when attempts are made in assigning therapeutic modalities indiscriminately to both the mandible and maxilla. In actuality the anatomic problems in each jaw differ dramatically and surgical differences abound. In the mandible more emphasis needs to be paid to inferior and posterior cortical bone relationships to the tumor to potentially avoid discontinuity resections of these benign lesions. With the exception of ameloblastoma, there are only a handful of reports of mandibular benign odontogenic tumors getting away from the surgeon into soft tissues or nearby bones. Yet a cookie cutter approach is often applied. Ameloblastoma-like therapeutic models are applied to many benign odontogenic tumors. I am not aware of any studies on the morbidities associated with nonameloblastoma recurrences in the modern world of imaging. Likewise, despite studies associated with the jaw resections and obturators (generally in cancer therapy),159-168 there are no studies on quality-of-life issues associated with benign odontogenic tumor therapy. Evidence to support recommended treatment margins is usually based on comparing recurrence rate with ameloblastomas, not the biologic behavior of the tumor. In addition, the 1-, 1.5-, and 2-cm margins recommended are often unclear. Regarding benign odontogenic lesions other than ameloblastomas, studies that have actually controlled for confirmed resection margins, pathologically and radiographically before and after surgery, are terribly lacking. For ameloblastomas Carlson and Marx169 do a credible job in advocating resection. They also account for frozen sections, biologic barriers, and utilization of intraoperative radiographs (Fig. 93-16). However, they fail to recognize the simple fact that the actual goals are to ensure and confirm tumor removal, not to have a one-size-fits-all guideline. They also discuss confusion about solid and nonunicystic cystic ameloblastomas. More discussion of this problem is provided later. Gardner does an excellent job on the problems of doing retrospective analysis of the literature on ameloblastomas.170 In the maxilla, 1-cm bony margins are sometimes recommended in the proximal-distal direction. However, the anatomy of the sinuses, nasal cavity, orbit ethmoids, and pterygoid plates in many instances makes the use of anatomic boundaries more appropriate. In general, one or two anatomic boundaries are sufficient to ensure excision. In all lesions, even the ameloblastoma, the periosteum is thought to be an effective tumor barrier.171 The interested lifetime/evidence-based learner is invited to perform a MEDLINE search of actual invasive benign odontogenic tumors. A 4-decade review by Leibovitch and colleagues172 found only 11 reported cases of ameloblastomas with orbital involvement. A MEDLINE search for this chapter revealed about the same amount of reports (using search terms of ameloblastoma combined sequentially with invasi, extension, and involve) revealed, in a cursory review of abstracts, approximately 25 to 40 cases/reports with the majority being from an original maxillary lesion. Without a doubt, soft tissue extension of recurrent ameloblastomas is a real problem, with Sampson and Pogrel documenting a high percentage of ameloblastomas involving soft tissues in a series of 26 cases.173 But the ameloblastoma is a special case and is covered more thoroughly later. The following section discusses general principles concerning the other odontogenic tumors. With the exception of malignant variants, the reports of other odontogenic tumors extending, involving, or invading other adjacent structures are extremely rare.

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1271

Figure 93-16. Intraoperative radiograph. Note that the posterior margin is closer than the desired 1-cm margin. Such intraoperative radiographs help obviate the inability to perform frozen sections on bony tissue.

In assessing the benign odontogenic tumors, it is essential to critically read reports on how margin measurements were defined and how those margin measurements were confirmed both intraoperatively and postoperatively. I know of no adequately described prospective report. For example, I believe such measurements are in relation to the medullary bone and do not necessarily imply cortical bone. Surgically and restoratively, the loss of thin cortical bone on the buccal, lingual, and alveolar aspects is different from losing the inferior border of the mandibular body, the posterior border of the ascending ramus, or for that matter the condylar head or condylar neck. In all cases, it is this authors plea to always ask first, Is there any realistic chance of this mandibular benign tumor getting away from me, if it recurs? Second, ask, Has the tumor already destroyed any of the critical structural elements of the mandible? Third, ask, Is there a reasonable chance of radiographic and patient follow-up? I believe the first question will result in the surgeon realizing that loss of critical bony structures is unnecessary in most cases and the cookie cutter approach can be modified for the patient at hand. In the second question, if the lesion has not already destroyed critical structures, there are probable criteria not to iatrogenically destroy them. A huge caveat to this is that the lesion must be far enough away from these important structural elements to allow for a radiographically clear margin on the resected specimen. The clear margin will also then need to be confirmed histopathologically. If critical structures have already been destroyed by the lesion, the surgical decisions are straightforward. In the third question there are probably as many reasons or more to follow a person with history of tumor, a segmental resection, and a graft as compared with patients at risk of a recurrence alone. There are no reports of recurrence rates dropping to 0% after segmental resection. The surgeon is urged to review the literature with an eye to evidence-based data. The maxillary lesions are more problematic due to the short distance needed to involve areas difficult to operate in and oblate the tumor. Such areas include but are not limited to the pterygoid plates, orbital floor, and pterygopalatine fissure. The head and neck surgeon realizes that in some areas any benign tumor is difficult to access and completely remove. Thus persistence of tumors in these areas is more a problem of location than of the inherent invasive potential of the tumor. Carlson and Marx169 do a good job of discussing biologic barriers in their article.

Figure 93-17. Photomicrograph of unicystic ameloblastoma with typical ameloblastomatous changes.

Unicystic Ameloblastoma

Unicystic ameloblastomas account for approximately 15% of all ameloblastomas. Unicystic ameloblastomas may be found in any odontogenic tissuebearing area. Most unicystic ameloblastomas are found in the posterior mandible. Unicystic ameloblastomas most often occur in the second and third decades, a somewhat younger population than reported for the solid ameloblastoma. As with other odontogenic cysts and tumors, unicystic ameloblastomas are usually asymptomatic unless secondarily inflamed.97 Radiographic Features Unicystic ameloblastomas present as radiolucent, unilocular lesions, with well-demarcated, corticated borders, indistinguishable from most odontogenic cysts or tumors. Many unicystic ameloblastomas appear to be dentigerous cysts both on radiographic and gross examination. However, they may be found in any location. Microscopic Features The microscopic features known as Vickers and Gorlin criteria define the unicystic ameloblastoma. These features are (1) columnar basilar cells, (2) palisading of basilar cells, (3) polarization of basilar layer nuclei away from the basement membrane, (4) hyperchromatism of basal cell nuclei in the epithelial lining, and (5) subnuclear vacuolization of the cytoplasm of the basal cells. Above the basal layer, loosely aggregated stellate cells resembling the stratum spinosum of a developing tooth are noted (Fig. 93-17).174 It is important to realize that some portions of unicystic ameloblastomas may not show all these features. A variation of unicystic ameloblastoma described by Gardner allows for a plexiform variant. Inflammation may disrupt the diagnostic features of unicystic ameloblastoma.175-177 As in all odontogenic cysts and tumors of the jaws, the entire specimen needs to be embedded because the treatment depends on the presence or absence of ameloblastomatous epithelium in the fibrous wall.

1272

Part 6 n Head and Neck Surgery and Oncology

Figure 93-18. Area in a generally cystic ameloblastoma where the tumor has invaded the connective tissue wall. This portends an increased risk of incomplete removal and thus recurrence.

Definitions, Clarifications, and Treatment Recommendations A unicystic ameloblastoma must be unilocular, as well as unicystic, and display the pathologic features of an ameloblastoma lining the lumen but not invade the connective tissue (Fig. 93-18). From the beginning, criteria have varied and caused confusion, but this definition applies in the following discussion. The unicystic ameloblastoma was separated from the standard ameloblastoma by Robinson and Martinez in 1977.178 The subtitle of that seminal paper was a prognostically distinct entity. Since that time the application of their original definition has been problematic, with others often further muddying the picture. A number of authors have attempted to provide evidence of predicted behavior for different types of unicystic ameloblastomas.178-183 The first premise in this chapters coverage of the unicystic ameloblastoma is that the only reason to separate the unicystic ameloblastoma is for therapeutic planning and expected clinical behavior. Ever since the original paper, it has been regrettable that multilocularity and connective tissue invasion were sometimes allowed within the diagnostic criteria. Ackermann and colleagues183 have analyzed unicystic ameloblastomas with connective tissue invasion as type 3. They found that they often recur if only enucleation is performed as therapy. For this reason, though, they should be more thoroughly studied and managed like a standard ameloblastoma. And thus separation as a unicystic ameloblastoma is spurious at best. Likewise, Philipsen and Reichart182 found that multicystic or multilocular cystic ameloblastomas recurred with simple enucleation. Again, this should make it clear that they should not be grouped under the designation of unicystic ameloblastoma. These features are seen in regular ameloblastomas, and determining where to draw the line of what is too much multilocularity or too much connective tissue proliferations is totally subjective and unwise unless future studies define a method to separate lesions. Until such studies, unicystic ameloblastomas should be considered as such only if they are unicystic and unilocular and display no connective tissue invasion. Some additional background information may also be helpful. Eversole and colleagues184 found recurrences more common (actually all four recurrences) in lesions larger than 2 cm. Unfortunately they did not stratify their data to state whether these larger lesions were multilocular or how the connective tissue wall was invaded.184 But this report implies that large or expansile lesions may recur even if the ameloblastoma is cystic. Likewise, a review of the original paper by Vickers and Gorlin,174 which defined the features of ameloblastomas, reveals that all their cases were recurrences of what today would have been diagnosed as unicystic ameloblastomas. Unicystic does not mean unilocular. Some authors allow for a multilocular radiographic appearance.185 These authors often use terms such as cystic or cystogenic instead of unicystic. Regardless, the intent is to attempt to group these lesions with the unicystic ameloblastoma. Some purport that histologically the multilocular lesion was unicystic

(how they confirm three dimensionally how a single cyst can make multiple locules and remain unicystic has never been adequately explained in my opinion). However, in my review of the literature, multilocularity increases the chance of recurrence and multilocular lesions should be at least enucleated and curetted rather than just enucleated. In my institution, multilocular and multicystic lesions would be signed out simply as ameloblastoma and presumed to be treated as such. Unilocular lesions may be histologically multicystic. Multicystic lesions are not unicystic lesions, so they should be considered standard ameloblastomas and treated as such. In their review of 193 unicystic ameloblastomas, Philipsen and Reichert182 found wide variations in definitions, nomenclature, and what lesions were included under the heading unicystic ameloblastoma. Simply put, the literature is horrible. Even separation of terms such as luminal, intraluminal, and mural varies among authors. As proposed originally by Robinson and Martinez,178 the reason for the diagnosis of unicystic ameloblastoma was to separate a prognostically distinct entity. Even in their report, Robinson and Martinez had a recurrence rate of about 20%. But they allowed for connective tissue nests, multilocularity, and large cysts. Two of their three lesions described as large dentigerous cysts recurred. Eversole and colleagues184 later used 2 cm as a cutoff for size because they found that larger cystogenic ameloblastomas had a propensity to recur with simple enucleation. Robinson and Martinez178 did not separate lesions by connective tissue involvement. But authors including Philipsen, Reichart, and Ackerman and colleagues (in various publications) have shown that connective tissue involvement is an important predictor of recurrence with simple enucleation. They designate these as what they call type 3 unicystic ameloblastomas and state that they tend to recur (i.e., behave like standard ameloblastomas if only enucleation is performed). Current wisdom is that the 20% recurrence rate of Robinson and Martinez may have been due to large size or connective tissue proliferations. Needless to say, inconsistencies have led to confusion. A goal of this chapter is to emphasize that the reason for the unicystic designation is to use the minimal amount of surgical intervention while minimizing the chance of recurrence. The literature is fairly clear that a subset of unicystic ameloblastomas can be managed with enucleation alone (or perhaps combined with minimal bony curettage). In this analysis the subset is the definition of unicystic ameloblastoma used.

Simple Unicystic Ameloblastoma

A unicystic ameloblastoma (referred to here as a simple unicystic ameloblastoma) requiring enucleation only must have the following characteristics: 1. Histologic features conform to criteria established by Vickers and Gorlin for the diagnosis of an ameloblastoma. 2. Radiographic evidence of a singular unilocular radiolucency exists. Definitive septation requires exclusion, so evidence of peripheral scalloping (except between tooth roots) may eliminate the possibility of a lesion being considered unilocular. 3. Intraoperative confirmation of unilocularity, any multilocular/multicystic characteristic, and cortical perforation or soft tissue involvement preclude interpretation of the lesion as unicystic. 4. Histologic features display only luminal or intraluminal involvement. Proliferation of the ameloblastoma into the fibrous connective tissue wall, whether plexiform or follicular, precludes diagnosis of the lesion as unicystic. 5. Size of the lesion must be less than 2 cm. I can only hope that further studies continue to define and separate the unicystic ameloblastomas, as well as delineate the line of when to designate a lesion as simply an ameloblastoma. Experience is available to justify the separation, and hopefully the science will follow.

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1273

Figure 93-19. Pantomograph with ameloblastoma in area where a third molar was extracted several years previously.

Ameloblastoma, Intraosseous Type*

Definition The ameloblastoma is a neoplasm of the enamel organ that recapitulates the cells necessary for tooth crown development. Intraosseous ameloblastomas arise from the lining of an odontogenic cyst, reduced enamel epithelium, or odontogenic rests. In the soft tissues of the oral cavity, specifically the gingiva or alveolar mucosa, they may arise from the basal cell layer. Those that arise from the overlying soft tissue are called peripheral ameloblastomas and are covered separately. In this chapter the three clinical types of ameloblastoma are unicystic ameloblastoma, peripheral ameloblastoma, and ameloblastoma. Here the modifiers of multicystic or solid are not used. They are not separated here because they are treated the same. Of these three, unicystic and peripheral have a much better clinical outcome after a conservative removal and assured margins. For clarification, I use the term intraosseous ameloblastoma to clarify that the lesion discussed is not peripheral. Intraosseous ameloblastomas occur in the mandible and maxilla with the mandible accounting for about 80% of all cases. In the maxillae, ameloblastomas may evolve in the maxillary sinonasal region, as well as during the alveolar process. The location of the tumor is an important factor in the long-term prognosis. Tumors that are in the anterior maxilla or body of the mandible or are confined to the mandible are less likely to cause significant problems. Conversely, those penetrating the mandible in the posterior ramus region and those of the posterior maxilla can extend into areas difficult to manage.186 Radiographic Findings Small ameloblastomas appear as a unilocular radiolucency with welldemarcated and at least partially corticated borders. These radiolucent lesions are indistinguishable from other cysts or benign tumors of the jaws (Fig. 93-19). Larger lesions may be easier to recognize radiographically. The classic description of larger lesions is a soap bubble or honeycomb appearance. Roots of adjacent teeth may show resorption in long-standing lesions. An ameloblastoma commonly displaces unerupted or erupted teeth. These radiographic features describe all histologic variants except for some desmoplastic ameloblastomas. In desmoplastic ameloblastomas of sufficient duration, a mixed radiolucent radiopaque lesion rather than a pure radiolucency may be seen. Additionally, the desmoplastic ameloblastoma is more common in the maxilla and anterior portion of the jaws.97 Microscopic Features Multiple microscopic subtypes of ameloblastoma exist. Although they are of importance to the pathologist, these histologic subtypes are not of therapeutic or prognostic importance. But in summary, histologic subtypes include follicular, plexiform, granular cell, acanthomatous, desmoplastic, basal cell, and keratinizing. The classic features of ameloblastoma were described by Vickers and Gorlin.174 These features are columnar basilar cells, palisading of basilar cells, polarization of basilar
*Includes solid types and all ameloblastomas that, although being cystic, do not conform to criteria within the unicystic ameloblastoma section. Figure 93-20. Photomicrograph of plexiform ameloblastoma with typical Vickers and Gorlin features. Stellate reticulum is also somewhat acanthomatous.

layer nuclei away from the basement membrane, hyperchromatism of basal cell nuclei in the epithelial lining, and subnuclear vacuolization of the cytoplasm of the basal cells. Above the basal layer, loosely aggregated stellate cells resemble the stratum spinosum of a developing tooth (Fig. 93-20). Natural History and Treatment Gardner pointed out two main factors that explain the behavior of ameloblastomas: (1) their ability to infiltrate medullary bone and a relative inability to infiltrate compact bone; (2) the location of the tumor. As noted earlier, tumors near vital structures such as the orbit or cranial base are much more difficult to control and pose greater clinical problems. Free margins of excision are difficult to obtain in ameloblastomas arising in the posterior maxilla. Dense compact bone such as that of the inferior border of the mandible or ramus acts as the first-line barrier.187 The outer periosteum appears to serve as a backup barrier to prevent tumor spread, but once it is broken, access to vital structures may occur.171 In the maxilla, only a thin cortical plate exists between contiguous bones and is generally thought of as a poor barrier to prevent the spread of ameloblastomas.169 Tumors of the posterior maxilla involving the orbit are the most difficult to treat and manage. Undoubtedly such lesions will present with unique and specific problems related to the individual case.188 Simple enucleation of ameloblastomas is not considered standard care in the United States. Even when it is combined with curettage, ameloblastomas are known to recur. Yet successful results with enucleation and curettage have been reported.189,190 The recurrence rate is thought to be due to the fact that ameloblastoma infiltrates the trabeculae of cancellous bone. The reported success with curettage (or peripheral ostectomy with rotary bur) is probably due to relatively efficient/ aggressive medullary bone removal. It is generally considered a fact that tumor infiltration frequently extends beyond the apparent radiographic margin. Ensuring even amounts of bone removal with enucleation and curettage can be difficult. Small bits of tumor may remain within the bone without the ability to assess margins grossly or histologically. It is thought that resection with adequate margin is the most predictable method to assure that the tumor will not recur. A resected specimen allows for intraoperative radiographic assessment of adequate margins and postoperative histologic confirmation of margins. Histologically simply clear margins are acceptable. How pathologists deal with resected bone specimens in the pathology laboratory is inconsistent. The surgeon should explicitly request that the entire bony specimen be demineralized and margins fully assessed. The surgeon should mark surfaces that are not margins such as the vestibule, gingiva, alveolar mucosa, and sinus mucosa. As a pathologist, I know how much

1274

Part 6 n Head and Neck Surgery and Oncology

work such requests entail. Although I dread these specimens coming into the laboratory, I believe this is the only way to assess therapy and plan for future reconstruction. What an adequate radiographic margin should be is more controversial and probably varies by case. Even after en bloc resections, reportedly well past radiographic evidence of tumor, recurrence rates of 10% to 15% have been reported. Although some surgeons advocate larger margins, the general consensus is that resection should be 1 cm past the radiographic limits of the tumor. Unfortunately, there are no wellcontrolled studies of radiographs of the resected specimen compared with postsurgical defects to actually confirm what margins were achieved. Likewise, although there are anecdotal reports, there are no controlled studies of resected specimens correlated with radiographs to assess how far the tumor actually extended histologically past that radiographic evidence. Carlson and Marx have made initial attempts to accumulate such data, but a well-documented study has not yet been performed.169 Due to the lack of reliable data, the following discussion is yet another anecdotal opinion on how to manage ameloblastomas.

dental lamina rests or basal cells of the overlying mucosa. Histopathologically the lesions appear as any of the previously mentioned variants, though the basal cell variant is the classic subtype. By definition these tumors do not infiltrate the underlying bone. If there is an intraosseous component, the lesion is not a peripheral ameloblastoma. If there is bone involvement, the lesion is treated as an intraosseous ameloblastoma. Peripheral ameloblastoma may become quite large. Lesions may be imaged with MRI or CT. Treatment is to assure excision with histopathologically confirmed margins.209-218

Malignant Ameloblastoma

Management of Mandibular Ameloblastomas

Malignant ameloblastomas are lesions that have any of the classic benign histopathologic features of ameloblastoma but metastasize to a distant location. In many cases the metastases are long delayed and may occur years after the initial tumor was treated. The lung is the most common site for metastases. Cervical lymph node involvement has also been reported. Treatment varies by degree and site of involvement. Though excision is preferred, radiotherapy may be the only practical option.219-224

One-centimeter medullary bone margins, referring to the proximal and distal directions, are preferred. Lingual and buccal cortical bone is sacrificed, but 1-cm margins do not imply inclusion of soft tissue outside the periosteum. In the mandibular body and in the anterior ramus overlying mucoperiosteum, teeth, gingiva, and mucosa are submitted with the resected specimen. In essence, portions of the bone resection specimen without muscle attachments will have overlying mucosal soft tissue included in the specimen. In the depth of the lingual and buccal vestibules, as well as the ascending ramus where muscle attachments begin, the periosteum will remain with the resection specimen. These periosteal surfaces will represent the surgical margins of the specimen. If the coronoid process is more than minimally undermined, it is also sacrificed (following detachment from the temporalis muscle) and included or separate from the main resection specimen. If extension is suspected past any periosteal surface, frozen tissue margin protocols should be applied and specimens should be handled separately. Assessing bone margins in maxillary bone resection specimens is even more important. Some authors recommend 1- to 2-cm margins in the maxillae. The larger end of the range is probably unnecessary in the anterior region and difficult to obtain when lesions approach the orbit or pterygoids, or both. Again, such margin recommendations pertain to attempted bony margins and not to soft tissues. Soft tissue margins must be assessed by frozen section or on properly oriented permanent sections. Treatment of maxillary lesions varies greatly and depends on both CT and MRI interpretation. Follow-up of maxillary lesions is extremely important and it is assumed that attempts to spare vision and vital structures of the region may alter initial treatment plans. Excision to extend two biologic barriers past the tumor serves as a rule of thumb. The en bloc specimen should be examined intraoperatively from multiple radiographic views. Final margin assessment occurs after demineralization. Though not often recommended, radiotherapy may occasionally play a role in unresectable tumors.191 Similar to the mandibular tumors, the periosteum above the level of muscle attachment is the surgical margin. Overlying mucoperiosteum, teeth, gingiva, and mucosa are submitted with the resected specimen.

Ameloblastic Carcinoma

Ameloblastic carcinoma, in contrast to malignant ameloblastoma, shows cytopathologic features associated with malignancy (e.g., increased mitotic activity, increased nuclear and cytoplasmic ratio, nuclear pleomorphism, hyperchromatism). The cytopathologic/histopathologic features allow for this being diagnosed in the primary location. The tumor may or may not metastasize, but like the primary tumor the cytopathologic features display the anaplastic features of malignancy. These are rare lesions.225-234

Ameloblastic Fibroma

Management of Maxillary Ameloblastomas

The ameloblastic fibroma is a benign odontogenic neoplasm characterized by proliferation of immature mesenchymal and ameloblastic cells, both of which are characteristic of a developing tooth. Unlike the ameloblastic fibro-odontoma or the odontoma (complex and compound), the ameloblastic fibroma does not have the capacity of producing enamel, dentin, or cementum. The tumor can be found in any toothbearing site. However, the tumor is most often seen in the premolarmolar region of the posterior mandible. There is no gender predilection, but the lesion is usually identified in a bimodal age distribution. The majority of lesions are diagnosed before age 20, though another smaller group of lesions is seen in middle age. As with other odontogenic neoplasms, the lesion is slow growing and asymptomatic unless secondarily inflamed. A firm expansion of the buccal cortical plate of the mandible or maxilla is the most common clinical finding. The lesions are most often small and unilocular. It is thought that an early version of odontoma necessarily goes through a stage that is histopathologically indistinguishable from an ameloblastic fibroma. Separating these early odontomas from a real ameloblastic fibroma is impossible. However, there are reports of large and destructive ameloblastic fibromas that clearly require the ameloblastic fibroma to be classified as a neoplasm rather than a hamartoma. The tumors that become large and destructive are perhaps more likely to be seen in older patients.235-239 Radiographic Features The ameloblastic fibroma usually presents as a well-defined radiolucency. The border is often corticated though sclerotic changes may also be seen. Small lesions are usually unilocular, whereas larger, more aggressive tumors are usually multilocular. The majority of lesions are seen in association with the crown of an unerupted tooth. Microscopic Findings The histopathologic features of an ameloblastic fibroma are characterized by the proliferation of both epithelial and mesenchymal elements. The mesenchymal component presents as a relatively cellular-young, basophilic, fibromyxoid tissue suggestive of a developing tooth pulp or dental papillae. The fibroblastic cells vary from stellate to spindled. Admixed within the mesenchymal background are islands, cords, or nests of odontogenic epithelium. The outer epithelial cells near the basement membrane become cuboidal and occasionally columnar, at

Summary

In summary, the ameloblastoma is the most aggressive of the benign odontogenic tumors. Numerous reports on treatment are available, but well-controlled prospective studies are necessary to answer many questions.126,173,187,189,192-208

Peripheral Ameloblastoma (Extraosseous Ameloblastoma)

Peripheral ameloblastomas present as mucosal masses and arise from the gingiva or alveolar mucosa. The actual proliferation may come from

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1275

Figure 93-21. Photomicrograph of follicles that are essentially identical to an ameloblastoma, but the background stroma is consistent with dental papilla. Eosinophilic induction effect is seen around a few epithelial islands.

Figure 93-22. Photomicrograph in which an area identical to an ameloblastic fibroma dominates the right side of the image, but mineralized products dominate the left side and confirm the diagnosis as an ameloblastic fibro-odontoma.

least focally. These islands are essentially identical to islands seen in follicular ameloblastomas. By definition, ameloblastic fibromas will have no areas of mineralization. If mineralization is seen, the lesion is actually an ameloblastic fibro-odontoma (Fig. 93-21).97 Treatment Conservative surgical enucleation of the tumor is the treatment of choice for all small, unilocular lesions. The tumor does not have the infiltrative margins characteristic of an ameloblastoma and therefore recurrence rates are low. With early detection and removal, the longterm prognosis is favorable. However, larger multilocular lesions may be destructive and reports of recurrence up to 40% were reported in a 1972 article from a series of cases at the Armed Forces Institute of Pathology.239 Segmental resection is not indicated in any tumor except those that have essentially already destroyed the integrity of the jaw involved.

Microscopic Findings

The histopathologic features of an ameloblastic fibro-odontoma are characterized by the proliferation of both epithelial and mesenchymal elements. The mesenchymal component presents as a relatively cellularyoung, basophilic, fibromyxoid tissue suggestive of a developing tooth pulp or dental papillae. Admixed in the fibromyxoid tissue are mineralized and premineralized elements including enamel, enamel matrix, dentinoid, dentin, cementoid, and cementum. Admixed within the mesenchymal background are islands, cords, or nests of odontogenic epithelium. These scattered epithelial components are identical to those seen in the ameloblastic fibroma (Fig. 93-22).243-246

Treatment

Ameloblastic Fibro-odontoma

The ameloblastic fibro-odontoma is a rare odontogenic tumor. The lesion has had some controversy in the literature in regard to its appropriate classification. Similar to the ameloblastic fibroma, it is thought that a maturing odontoma necessarily goes through a stage that is histopathologically indistinguishable from an ameloblastic fibroodontoma. However, reports of large and destructive ameloblastic fibro-odontomas clearly confirm its ability to act as a neoplasm rather than a hamartoma. The majority of patients with ameloblastic fibroodontoma are young, with a mean age of 10 years. Whether these data are skewed from improper inclusion of maturing odontomas is difficult to assess. Undiscovered tumors can cause significant cortical plate expansion. Most are discovered during other radiographic studies or when a tooth has failed to erupt. Occasionally the tumor can persist or recur. It is probably most prudent to assess the individual tumor and patient in its context. If the tumor is large and destructive, it is more likely to be acting neoplastically. Multilocular tumors should be assumed to be neoplastic.97,240,241

Small ameloblastic fibro-odontomas are generally treated with simple enucleation. Multilocular lesions should be additionally treated with curettage/peripheral ostectomy with a rotary instrument. Unerupted teeth associated with the tumor may be retained. Depending on the amount of displacement and root development, they may or may not need orthodontic intervention to ensure eruption. Very large, inherently destructive lesions require complete but conservative surgical removal. Recurrences have been reported but are extremely rare. Segmental resection is not indicated in any tumors except those that have essentially already destroyed the integrity of the jaw involved.247,248

Epithelial Odontogenic Ghost Cell Tumor (Dentinogenic Ghost Cell Tumor, Odontogenic Ghost Cell Tumor)

Radiographic Findings

The tumor is a well-circumscribed, unilocular or multilocular lesion.242 Though evidence of mineralization must be present histopathologically to make the diagnosis, the mineralizations will not always be evident radiographically. Therefore early lesions may be radiolucent. The amount of mineralization varies widely.

In conjunction with this brief section, please refer to the earlier discussion on the calcifying odontogenic cyst. The epithelial odontogenic ghost cell tumor is an unusual jaw lesion that consists of a complex (at least focally), solid, tumor-like mass, though a cystic area is usually present as well. As with other odontogenic neoplasms and cysts, the lesion can occur in any tooth-bearing site. Most reports indicate that the lesion occurs most often in the posterior mandible. Most lesions arise centrally within bone; however, lesions may be identified as arising peripherally within the gingiva. Extensive data on these tumors is scarce but is assumed to have a similar age distribution as the calcifying odontogenic cyst. Terms such as malignant and aggressive have been appended to this diagnosis. Personally the malignant appendage should only be

1276

Part 6 n Head and Neck Surgery and Oncology

Figure 93-23. Radiograph of a large calcifying epithelial odontogenic tumor displacing a premolar and having a mixed radiographic appearance.

Figure 93-24. Gross specimen showing the gelatinous nature of an odontogenic myxoma.

used in cases where cytomorphologic characteristics of malignancy are noted. Aggressive lesions are identified by inherent destructive behavior or recurrence. Central bony lesions usually present as a firm, expansile mass of the buccal cortical plate. The lesions are asymptomatic unless secondarily inflamed. Gingival lesions appear as a firm, smooth, sessile, soft tissue enlargement involving the attached gingiva or edentulous alveolar ridge. These peripheral masses may present on either the buccal or lingual aspect.139,140,249-261 Review of the International Collaborative Study on Ghost Cell Tumours is a must-read when one of these lesions is encountered.139 A pathologist well versed with all forms of this tumor should be consulted for proper classification.

treated with simple enucleation and curettage. Very large or inherently destructive lesions require complete but conservative surgical removal. Recurrences have been reported. Segmental resection is not indicated in any tumors except those that have essentially already destroyed the integrity of the jaw involved. Tumors with clear cell changes may be more clinically aggressive than standard tumors. Tumors with cytopathologically malignant features should be considered separately.266

Odontogenic Myxoma

Calcifying Epithelial Odontogenic Tumor (Pindborg Tumor)

The calcifying epithelial odontogenic tumor is an unusual odontogenic neoplasm characterized by sheets of hyperchromatic, pleomorphic cells with foci of amyloid and mineralization. Calcifying epithelial odontogenic tumors occur more often in the mandible than the maxilla with a ratio of about 2 : 1. Within the arch, they are often located in the molar-premolar region. As with other odontogenic tumors, they may or may not be associated with unerupted tooth crowns. Those seen in the second decade are often associated with an unerupted tooth. The tumors are rare but have been reported more often in males. The tumor most often occurs in the third through fifth decades.97 This tumor is rarely seen peripherally as a gingival mass or alveolar ridge mass.262,263

The odontogenic myxoma is a relatively uncommon, benign neoplasm apparently arising from the mesenchymal portion of the tooth-forming unit known as the dental papillae/dental sac. Odontogenic myxomas have been identified most often in the posterior tooth-bearing areas of the dental arches and present in both upper and lower jaws. The mandible is more commonly involved than the maxilla. Most tumors are identified during the second or third decades of life. No gender predilection has been identified. As with other odontogenic neoplasms, clinical findings usually consist of a smooth, bony, hard expansion of the alveolus. The primary process of the odontogenic myxoma is to infiltrate through medullary spaces. Intraoperatively the myxoma is seen as gelatinous material (Fig. 93-24). Judging where the gelatinous material ends intraoperatively and especially radiographically may be difficult. In some instances odontogenic myxomas do penetrate the cortex. They have also been reported as forming outside the body of the mandible, in which case they would present as a smooth-surfaced gingival enlargement.97,267-271 As with many other odontogenic neoplasms, an odontogenic myxoma may present as either a unilocular or multilocular radiolucency. Most lesions show radiolucency with variable cortication. When the cortical bone is penetrated, a periosteal reaction may result in apparent osseous production. Residual or reactive bone may also be seen intraosseously272 and give a somewhat mixed radiopaque/radiolucent appearance. Cone beam CT may be helpful.273 When residual bone is somewhat organized, the appearance has been described as similar to either a honeycomb or tennis strings.274

Radiographic Findings

The tumor is usually well circumscribed with a multilocular appearance being more common than a unilocular lesion. Though evidence of mineralization is often present histopathologically, radiographically the mineralizations will sometimes not be evident. However, this is one of the classic mixed radiolucent-radiopaque lesions of the jaws. The amount of mineralization varies widely with some lesions having minimal evidence of radiopacity (Fig. 93-23). The peripheral lesions may produce a cupping effect of the underlying bone. In these instances the cupping is thought to be secondary to pressure resorption. The tumor is characterized by islands and sheets of epithelial cells dispersed throughout a nonspecific fibrous stroma. In many instances the polygonal, epithelial cells show remarkable pleomorphism and nuclear hyperchromasia. Borders of the epithelial cells are well defined and prominent intracellular bridges are characteristic. The cytoplasm is often strikingly eosinophilic, but tumors may display a prominent clear cell component.264,265 Foci of homogeneous eosinophilic amyloid may be present.

Radiographic Findings

Microscopic Findings

Microscopic Findings

Odontogenic myxomas are characterized by a relatively acellular myxoid tissue. Occasional strands and cords of odontogenic epithelium may be noted, but these rests are not seen in all neoplasms. Tumors may be somewhat collagenous/fibromatous, but the myxomatous features should dominate the histopathologic picture.

Treatment and Prognosis

Treatment

Conservative surgical excision is the treatment of choice for the extraosseous variant. Small unilocular and multilocular lesions are generally

Due to the loose, gelatinous nature of the tumor, surgical enucleation can be difficult to judge. However, the odontogenic myxoma is another lesion where the tumor has not been reported to get away from the surgeon on recurrence. The goal of treatment should center on removal of medullary bone well past the radiographic borders. Recommenda-

Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors

1277

The tumor consists predominantly of spindle-shaped epithelial cells that form whorled masses or rosettes in a scant fibrous stroma. Ductlike structures lined by cuboidal or columnar epithelial cells are the classic histopathologic feature. Foci of amyloid, if present, are usually seen in the rosette/adenomatoid arrears. Other mineralized material may also be seen. These mineralizations are usually not well organized but may resemble dentin, cementum, or aborted attempts at enamel production.280-282 Cystic spaces are also common. Some may be true luminal surfaces, though the largest surface lumen is probably adjacent to the tooth crown.

Microscopic Features

Treatment

These lesions are very well encapsulated and therefore easily enucleated. Aggressive behavior is never anticipated and recurrence is not a problem, though large lesions have been reported.276 The lesion can be enucleated and the tooth can be left in place for eventual eruption or orthodontic therapy.

Odontomas
Figure 93-25. Although originally apparently small, intraoperatively gelatinous material was at resected margins, which necessitated successive removal of additional bone. Gelatinous material is not well seen on these fixed specimens.

tions of how much medullary bone to remove vary,271,275 but 0.5 to 1 cm of medullary bone removal appears to be prudent. Removal of cortical bone in areas of penetration is also recommended. Recurrence rates can vary significantly from case to case and often show a direct correlation with the size of the lesion at initial diagnosis. Large and clinically aggressive tumors may necessitate segmental resection. In such cases the surgery is derived not from the diagnosis but by the nature of the lesion at hand. Intraoperative radiographs as described in treatment of ameloblastomas are also appropriate. Confirmation of margins histopathologically is also essential before reconstruction. Grossly the gelatinous material may also be easily seen at resected margins intraoperatively (Fig. 93-25).

Odontomas are the most commonly diagnosed odontogenic tumors. They are considered by many to be a hamartoma rather than a true neoplasm. Odontomas are subdivided into two subtypes: complex and compound odontomas. Complex odontomas, when fully developed, consist almost entirely of intermingled aggregates of enamel, enamel matrix, dentin, and cementum arranged in a haphazard manner. Compound odontomas consist of enamel matrix, dentin, and cementum. Unlike the complex odontoma, the mineralized elements are organized with the overall appearance suggestive of multiple small, malformed, but easily identifiable teeth. These toothlike elements can easily be seen at the grossing table. Some epithelial elements may be seen peripherally. These epithelial cells represent the reduced enamel epithelium from which the hard tissues were formed. Odontogenic rests are also seen peripherally. Just as with an unerupted tooth, these epithelial linings and rests may lead to formation of dentigerous cysts. Likewise, any odontogenic cyst or tumor may also develop in association with an odontoma. Complex and compound odontomas occur with equal frequency and some lesions show features of both subtypes. Depending on size and location, they may deform adjacent teeth or delay eruption.97,283,284

Adenomatoid Odontogenic Tumor

The adenomatoid odontogenic tumor is a relatively infrequent odontogenic tumor that has vague histologic similarities to ameloblastoma. Unfortunately the histologic similarity led to past nomenclature as adenoameloblastoma or ameloblastic adenomatoid tumor. The vague microscopic similarity is this tumors only similarity with that more aggressive tumor. Clinically the adenomatoid odontogenic tumor is by far the most innocuous odontogenic tumor, at least if the odontoma is considered a hamartoma. It appears that the tumor derives from the enamel organ epithelium but may arise from dental lamina rests. Though the actual ratio varies slightly by report, the adenomatoid odontogenic tumor is often known as the two-thirds tumor because it occurs two thirds of the time in females and two thirds of the time in the maxilla. Two thirds of the time this tumor is associated with impacted teeth (especially the canine), and two thirds of these tumors are found in teenagers. It is unusual in patients older than 30 years of age. Occasionally an adenomatoid odontogenic tumor arises peripherally within the gingiva. It is most often discovered radiographically when exploring the reason that a canine has not erupted long after its contralateral partner.97,276-279

Radiographic Findings

Both complex and compound odontomas show a well-demarcated radiolucency with a uniform corticated border delineating the lesion from surrounding bone. This has been described as a well-defined central radiopacity(s) surrounded by a thin radiolucent line surrounded by a thin radiopaque line. This is exactly the description of an erupting tooth. Centrally, there are differing brightness values associated with the radiopacities. The variation is due to the fact that enamel is more radiopaque than the dentin and cementum. Dentin and cementum cannot be differentiated radiographically. Compound odontomas will be a sack of teeth, and complex odontomas will be a disorganized aggregate.

Microscopic Findings

Radiographic Features

The adenomatoid odontogenic tumor usually presents as a unilocular radiolucency with a sharp, circumscribed border. The border is well corticated to sclerotic. It is often associated with an uninterrupted tooth. The radiographic feature of the tumor blending with a follicle can sometimes be confused radiographically with a dentigerous cyst. Although purely radiolucent lesions are most common, this is another one of the classic radiolucent/radiopaque lesions of the jaws.

Complex odontomas, when mature, consist almost entirely of a conglomeration of dentin, cementum, and enamel matrix. Following demineralization, the areas of mature enamel are lost and appear as empty spaces. In complex odontomas only scant amounts of reduced enamel epithelium remain. Peripherally, follicular tissue and odontogenic rests are common. During the demineralization process necessary for routine microscopic sectioning, the enamel portion of the specimen will be reduced to a retracted and fragmented, homogeneous, basophilic material. Less than 1% of the enamel is organic, and only this 1% is observed following demineralization procedures.

Treatment

Complex and compound odontomas are treated with simple enucleation and avoidance of damage to adjacent structures and teeth. If the term never can be used in health science, then odontomas never recur.

1278

Part 6 n Head and Neck Surgery and Oncology Finkelstein MW. Overview of general embryology and head and neck development. In: Bishara SE, ed. Textbook of Orthodontics. Philadelphia: WB Saunders, 2001:2-24. Franklin CD, Pindborg JJ. The calcifying epithelial odontogenic tumor. A review and analysis of 113 cases. Oral Surg Oral Med Oral Pathol. 1976;42(6):753-765. Gorlin RJ. Nevoid basal cell carcinoma (Gorlin) syndrome. Genet Med. 2004;6(6):530-539. Lau SL, Samman N. Recurrence related to treatment modalities of unicystic ameloblastoma: a systematic review. Int J Oral Maxillofac Surg. 2006; 35(8):681-690. Nakamura N, Higuchi Y, Mitsuyasu T, et al. Comparison of long-term results between different approaches to ameloblastoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;93(1):13-20. Neville BW, Damm DD, Allen CM, et al. Odontogenic Cysts and Tumors. Oral and Maxillofacial Pathology. 2nd ed. Philadelphia: WB Saunders; 2002, 589-642. Philipsen HP, Reichart PA. Unicystic ameloblastoma. A review of 193 cases from the literature. Oral Oncol. 1998;34(5):317-325. Philipsen HP, Reichart PA, Nikai H, et al. Peripheral ameloblastoma: biological profile based on 160 cases from the literature. Oral Oncol. 2001;37(1):1727. Philipsen HP, Reichart PA, Praetorius F. Mixed odontogenic tumours and odontomas. Considerations on interrelationship. Review of the literature and presentation of 134 new cases of odontomas. Oral Oncol. 1997;33(2): 86-99. Philipsen HP, Reichart PA, Slootweg PJ, et al. Odontogenic tumours. In: Barnes L, Eveson JW, Reichart PA, Sidransky D, eds. Pathology and Genetics: Head and Neck Tumours (World Health Organization Classification of Tumours). Lyon, France: IARC Press; 2005:283-328. Philipsen HP, Reichart PA, Zhang KH, et al. Adenomatoid odontogenic tumor: biologic profile based on 499 cases. J Oral Pathol Med. 1991;20:149-158. Shafer WG, Hine MK, Levy BM. Cysts and tumors of odontogenic origin. A textbook of oral pathology. 4th ed. Philadelphia: WB Saunders; 1983, 318-339. Shear M, Altini M. Odontogenic and non-odontogenic cysts of the jaws. J Dent Assoc S Afr. 1983;38(9):555-560. Slootweg PJ. An analysis of the interrelationship of the mixed odontogenic tumorsameloblastic fibroma, ameloblastic fibro-odontoma, and the odontomas. Oral Surg Oral Med Oral Pathol. 1981;51:266-276. Stoelinga PJ. Long-term follow-up on keratocysts treated according to a defined protocol. Int J Oral Maxillofac Surg. 2001;30(1):14-25. Ten Cate AR. Development of the tooth and its supporting tissues. In: Ten Cate AR, ed. Oral Histology. 3rd ed. St. Louis: Mosby; 1989:57-79. Vickers RA, Gorlin RJ. Ameloblastoma: Delineation of early histopathologic features of neoplasia. Cancer. 1970;26(3):699-710. Voorsmit RA. The incredible keratocyst. 315-323. 1984. University of Nijmegen. Ref Type: Thesis/Dissertation. Wright JM. The odontogenic keratocyst: orthokeratinized variant. Oral Surg Oral Med Oral Pathol. 1981;51(6):609-618.

This tumor is mentioned briefly because it is extremely rare with fewer than 100 ever reported. The lesions are generally small and usually present as inverted periodontal bone loss. Gingival tumors have also been described.285,286 That is, in periodontal disease the triangular base is toward the cementoenamel juntion. In the squamous odontogenic tumor the base is toward the tooth apex. Familial and multifocal cases have been reported. Any portion of the tooth-bearing area may be involved, and the paucity of cases does not allow for much demographic analysis. The importance of the tumor is that the squamous epithelial islands seen microscopically may be misinterpreted. The squamous islands are cytopathologically totally benign. Yet their presence deep in connective tissue may be misinterpreted as invasion. The invasive appearance may lead to misdiagnosis as either an acanthomatous ameloblastoma or, worse, a squamous cell carcinoma. Tumors are easily treated with enucleation and simple conservative curettage.286-289 Squamous, odontogenic, tumor-like proliferations are well known as being occasionally associated with inflammatory odontogenic cysts. These proliferations are inconsequential and do not warrant additional treatment or diagnostic proclamation.290-292

Squamous Odontogenic Tumor

Controversy surrounds the definition of odontoameloblastoma, and several lesions have likely been described under this designation. One subset of lesions given the moniker of odontoameloblastoma most likely represents an ameloblastoma arising from the epithelial elements of an odontoma. Other reports describe aggressive, large tumors that would be difficult to separate histologically from an aggressive ameloblastic fibro-odontoma.293-295 One report of dentinoid production with an ameloblastoma could be an additional subset.296 LaBriola and colleagues297 also reviewed the difficulties associated with this diagnosis and reported one case, as did other researchers.298,299 Generally these tumors define themselves by their destructive and/or recurrent behavior. Because of difficulties in histologic criteria, the diagnosis should always be made in consultation with a pathologist well versed in head and neck/oral pathology.

Odontoameloblastoma

SUGGESTED READINGS
Ackermann GL, Altini M, Shear M. The unicystic ameloblastoma: a clinicopathological study of 57 cases. J Oral Pathol. 1988;17:541-546. Baden E. Odontogenic tumors. Pathol Annu. 1971;6:475-568. Brannon RB. The odontogenic keratocyst. A clinicopathologic study of 312 cases. Part ii. Histologic features. Oral Surg Oral Med Oral Pathol. 1977;43(2):233-255. Daley TD, Wysocki GP, Pringle GA. Relative incidence of odontogenic tumors and oral and jaw cysts in a Canadian population. Oral Surg Oral Med Oral Pathol. 1994;77:276-280. Ellis GL. Odontogenic ghost cell tumor. Semin Diagn Pathol. 1999;16(4):288292. Eversole LR, Sabes WR, Rovin S. Aggressive growth and neoplastic potential of odontogenic cysts. With special reference to central epidermoid and mucoepidermoid carcinomas. Cancer. 1975;35:270-282.

For complete list of references log onto www.expertconsult.com.