Flint Cumming Otolaryngology CHAPTER 93 – Odontogenesis Odontogenic Cysts and Odontogenic Tumors

8/2/2019 Flint Cumming Otolaryngology CHAPTER 93 Odontogenesis Odontogenic Cysts and Odontogenic Tumors

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CHAPTER NINETY-THREE

Odontogenesis, Odontogenic

Cysts, and Odontogenic TumorsJohn 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 benecial for the reader to review Box 93-1 as an aid in formulating differential diagnosis lists.

The keratinizing odontogenic cyst is specically 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 identicalto 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 deniton.

For odontogenic tumors, in general readers are encouraged to always look over the general treatment considerations for each

patients situation. Specically 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 non-neoplastic lesions. Even the simple odontogenic lesions have theirorigin traced back to odontogenesis. But odontogenesis is far fromsimple. By understanding odontogenesis, the readers appreciation forthese lesions should be enhanced. In fact, it is the unique interactionof ectomesenchymal tissues with epithelial tissues during odontogenesisthat make these cysts and tumors unique. These interactions of themesenchyme and epithelium occur across short distances and withinthe conned volume of the jaws. Complications in histologic interpre-tation include artifacts caused by demineralization, sampling errors,separation of hard and soft tissues at the grossing bench, and generaldifculties in sectioning disparate tissue types. Separation of disparatetissue at the grossing bench can make it impossible to analyze therelationship of tissues later under the microscope. Even when thesebackground problems are not encountered, the result is often still ahistopathologic hodgepodge. In the end, odontogenic lesions that

contain both epithelial and mesenchymal components are often dif-cult to assess histologically.

A basic understanding of odontogenesis by the surgeon/clinicianmay help to predict behavior, enlighten the clinician on what informa-tion to give the pathologist, and guide proper treatment. Thus odon-togenesis and the jaws unique status within the body create a wide setof possibilities for clinical, radiographic, and histopathologic differen-tial 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 thischapter that a better understanding of odontogenic cysts and tumors

will lead to a more thorough appreciation of this intricate and compli-cated set of diseases.

BackgroundOdontogenesis begins within generally well-dened areas of the stomo-deum, then by maturational extension the oral cavity and alveolar


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1260 Part 6 n Head and Neck Surgery and Oncology

epithelial root sheath. Hertwigs root sheath as it moves apically to guideroot formation will leave behind epithelial rests known as rests of

Malassez. These rests will reside in the region of the periodontal liga-ment and provide a basis for several potential odontogenic cysts andtumors.

The periodontal ligament is actually a joint known as agomphosisjoint. Though the cementum cannot be distinguished except by loca-tion, the body, for instance, during orthodontic movement will resorbthe bone on the lamina dura side of the periodontal ligament and notthe cementum on the tooth side of the ligament. The tooth with the

periodontal ligament will retain a certain amount of mobility withinthe joint. The reader is again referred to various texts for a more in-depth coverage of odontogenesis.1-5,5a

SummaryThere are a number of odontogenic epithelial stages and each mayprovide a basis for odontogenic cysts or tumors. The four main stagesconsidered are (1) dental lamina, (2) enamel organ, (3) reduced enamelepithelium, and (4) Hertwigs epithelial root sheath. The rests ofSerres and Malassez are considered along with their respective pro-genitors of the dental lamina and Hertwigs root sheath. In addition,the stomodeal epithelium gives rise to Rathkes pouch, which retainsodontogenic potential. Shafer and colleagues6 suggest the originalbasal epithelium of the stomodeum also retains potential. In theadult this basal epithelium is represented by the gingival and alveolar

mucosal surfaces.6 This concept seems to be supported when periph-eral ameloblastomas appear to develop directly from overlyinggingival epithelium. With that said, most clinicians would consider theadult basal epithelium to be a rare source of odontogenic neoplasia.The rests of Malassez are common sources of inammatory odon-togenic cysts but retain little neoplastic potential. The rests of Serres,the enamel organ, and reduced enamel epithelium are generally con-sidered the stages most likely to become neoplastic. All stages have thepotential to form cysts but to variable degrees. Dentigerous cysts withtheir origin from the reduced enamel epithelium and radicular cystsfrom rests of Malassez make up the overwhelming majority of odon-togenic cysts.

Odontogenic Cysts

ClassicationWhen reading various sources it becomes quickly clear that what a cystis varies by author and that the classication schemata are in disarrayas well. The modied classication scheme seen in Box 93-1 is myattempt at organization. The odontogenic cyst of undetermined originis a new, admittedly descriptive diagnosis used by some oral pathol-ogists. Unfortunately the descriptive nature of that term will not beavailable to look up in other texts or journals. However, it replaces thediagnosis of primordial cyst. The need to use a descriptive term insteadof primordial cyst is due to the ambiguous use of primordial cyst bothas an odontogenic keratocyst (OKC) and a simple nonkeratinizing cystthat cannot be classied in relation to the tooth. The descriptive roleis to provide a pigeonhole in which to place lesions that are histologi-cally ambiguous, not directly associated with a tooth but located in thealveolus and thus presumably odontogenic in origin.

Several classication schemata for odontogenic cysts and oral andmaxillofacial cysts exist.7-9 The classication scheme seen here is modi-ed from that of the World Health Organization (WHO). In 1992

WHO published the second edition ofHistological Typing of Odon-togenic Tumors.10 Unfortunately the most recent WHO treatise onodontogenic tumors is contained within the Pathology and Genetics ofHead and Neck Tumors.11 In this change odontogenic cysts are nolonger covered within the text. Box 93-1 also contains selected non-odontogenic cysts for completeness and comparison.

By denition a cyst is considered a pathologic cavity at leastpartially lined by epithelium. To be an odontogenic cyst the epithe-lial lining must be derived from odontogenic epithelium. The bestadvice to the reader is that all classication schemata are articialto some extent. The key is to organize them the way that is mostuseful to you. This modication in Box 93-1 is an attempt at self-

processes of the jaws. Unfortunately, simply knowing the location doesnot necessarily allow the clinician to always positively ascertain a lesionas being odontogenic in origin. Confounding elements include theembryologic nature of Rathkes pouch, extension of large odontogeniclesions outside the connes of the alveolar processes, and the propensityof products of odontogenesis to wander. Thus reports of sinonasalameloblastomas and craniopharyngiomas of the sella should not besurprising and still be considered odontogenic in origin. Simply put,the only prerequisite is that all odontogenic cysts and tumors must bederived from elements of stomodeal origin.

Histologically the rather unique epithelial portions of odontogen-esis often remain distinct enough in cysts and tumors to allow forproper determination of origin. Unfortunately, the mesenchymal com-ponents of the dental papilla (as seen in myxomas) and cementalcomponents (as seen in odontogenic bromas) are impossible to den-itively identify histologically as being of odontogenic origin. The onlyhope in identifying these as odontogenic is if they occur in association

with other odontogenic epithelial elements. But generally, these mes-enchymal lesions are identied as odontogenic on the basis of theirlocation in the jaws.

Though this section focuses only on odontogenesis, rememberthat the oral and maxillofacial region is also associated with develop-mental remnants of salivary glands, seromucous glands, sinonasal epi-thelium, nasopalatine duct epithelium, and dermal epithelia. Due tothese nearby, possibly confounding embryologic tissues, the true origin

of any given lesion may be cloudy at best. However, by knowing thespecic location, history, and histopathologic features and being addi-tionally armed with knowledge of odontogenesis, the proper designa-tion for any given lesion can almost always be ltered to arrive at arelatively short differential diagnosis list.

The enamel organ is generally divided into the bud stage, capstage, and bell stage. The bud stage begins as a proliferation of thebasilar cells of the stomodeum. This proliferation occurs along the areaof the future alveolar mucosa apical to and separated from the vestibu-lar mucosa. In this early stage the ectoderm of the stomodeum is linedby two to three cells. It is during the sixth week that the ectoderm inthe region of the future alveolar processes begins to proliferate and formtwo somewhat horseshoe-shaped epithelial bands. Before being differ-entiated into the epithelial surfaces of the alveolar processes, each bandis called a dental lamina. These dental laminae will eventually form the

20 separate proliferations necessary for the deciduous teeth. These 20areas of proliferation are each called tooth buds. Each tooth bud thenproliferates apically into the underlying ectomesenchymal tissue. Even-tually at the bell stage the connection between the overlying stomo-deum and the enamel organ will become separated. But the actualprocess of bud proliferation varies by arch, as well as by tooth type (i.e.,deciduous central incisor, deciduous lateral incisor, deciduous canine,deciduous rst molar and deciduous second molar). By the end of theeighth week all 20 buds have been produced.

During all phases of morphodifferentiation, histodifferentiation,and apposition the features of the enamel organ and the physiologicsupport of the enamel organ are changing. But with apposition of thedentin and vascularization near the outer enamel epithelium the enamelorgan is further dened with a fourth cell layer termed the stratumintermedium. The cells of the stratum intermedium occupy an ill-dened area of attened cells between the inner enamel epithelium andthe stellate reticulum. Though the area of phenotypic change thatdenes the stratum intermedium must be present before enamel can belaid down, actually identifying these cells individually is extremelysubjective.

Root DevelopmentIn the tooth root, the dentin forms the huge majority of the rootvolume, which is then sheathed in a layer of cementum instead ofenamel. But the odontoblasts still cannot lay down dentin withoutinduction by epithelium derived from the enamel organ. To accom-plish this feat as the reduced enamel epithelium reaches the cemento-enamel junction, it becomes reduced to back-to-back inner and outerepithelial cells. This produces a collar of cells that separate from thereduced enamel epithelium. This separated collar is known as Hertwigs


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Chapter 93 n Odontogenesis, Odontogenic Cysts, and Odontogenic Tumors 1261

*Primordial cyst specically not used synonymously.

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.)

Inammatory cysts

Periradicular cysts

Periapical cyst (apical periodontal cyst)

Lateralized periradicular cyst

Residual cyst

Dentigerous origin

Periapical origin

Paradental cyst

Mandibular infected buccal bifurcation cyst

Inammatory 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 reclassied 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)

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


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Radiographic Features

Periapical cysts present as a unilocular radiolucency at the apical portionof the tooth. Though well dened, the border varies from corticated tosclerotic to merely well dened. Variations depend on the amount ofinammation present. Long-standing, neglected lesions can get quitelarge, though most are less than 1 cm in diameter (Fig. 93-1).

Microscopic Features

This is the classic inamed common odontogenic cyst and as suchthe luminal lining will consist of nonkeratinized stratied squamousepithelium. This is an inammatory cyst and inammation is invariablypresent if sufcient sampling is performed (Fig. 93-2). Rests of Malas-sez are possible in the connective tissue. However, odontogenic restsare rarely seen in the cyst wall even though these rests are thought tobe the source of the epithelial proliferation. Cholesterol slits, foreignbody giant cells, and hemosiderin deposits are common ndings. As inall common odontogenic cysts, squamous odontogenic tumor-likeproliferations may be seen in long-standing lesions. These epithelialislands will be cytopathologically benign without evidence of dysplasia.If squamous odontogenic cystlike proliferations are noted, they shouldessentially be ignored and are of no prognostic signicance. In endo-dontically treated teeth, foreign bodies secondary to endodontic therapyare common.47 Bacterial colonies may also be seen in these cysts.Though actinomycetes colonies may portend a tendency for being slow

Figure 93-1. Occlusal radiograph of large periapical cyst associated

with two endodontically treated maxillary incisors.

Figure 93-2. Photomicrograph of periapical cyst showing nonkeratiniz-ing stratied squamous epithelium with inammation. Cholesterol slits

are seen toward the left side of the luminal surface and appear as

empty white clefts.

clarication and will hopefully be useful for others in either its pure ormodied form.

PathogenesisMany odontogenic cysts are surfaced by nonkeratinized epithelium.Histologically the following nonkeratinizing cysts can look identical andcannot be separated except by clinical, historical, and/or radiographicmeans. These include dentigerous cyst (follicular cyst), eruption cyst,odontogenic cyst of undetermined origin, periapical cyst (apical periodon-tal cyst), lateralized periradicular cyst, residual cyst, and paradental cyst.

These cysts make up the majority of odontogenic cysts. As a groupthey are known as the common odontogenic cysts. For proper diagnosisof these common odontogenic cysts the clinician must provide suf-cient information for the diagnosis to be made. The reader is urged toclosely note the necessary or signicant features when each of these cystsis specically discussed later in this section.

The other odontogenic cysts will display histologic features toallow for the proper diagnosis, though history and communication areof course always appropriate and often essential. It is important to notethat the presence of a specic type of keratin is not pathognomonic foran OKC and may be seen with other odontogenic cysts.

Cyst expansion occurs because of numerous factors includingaccumulation of inammatory cells, brin, serum, and desquamatedepithelial cells. As these products enter the cystic cavity, it is the accu-mulation of the intraluminal products that spurs the cystic expansion

of the wall.12-14 Alternatively, cyst expansion may be spurred on by theinherent mitotic activity of the cyst wall itself. If this mitotic activity isthe major component of the cyst expansion, it may be better to considerthe lesion a cystic neoplasm rather than a simple cyst.14-20 This debatelies at the center of how to classify the OKC, as well as the calcifyingodontogenic cyst.21 In the case of the OKC, WHO has renamed it thekeratocystic odontogenic tumor. Discussion of this entity is in the odon-togenic cyst section. In the case of the calcifying odontogenic cyst (thetumor version), the reader is referred to more detailed articles on theepithelial odontogenic ghost cell tumor.

Multilocularity may in itself be a signal that the lesional growth ismitotically or multifocally driven rather than hydraulically driven.22-25For this reason the potentially multilocular odontogenic cysts, such asthe botryoid odontogenic and glandular odontogenic cyst, may argu-ably have a neoplastic potential as well.22,26-30 However, in the case of

the botryoid cyst the possibility of multifocality cannot be ignored. Cellregulation protein studies to determine cell inhibition and divisionactivities may be helpful in future classications.31,32 In addition, theability of epithelia to break down elements of the connective tissue wallcould be important.33-37

However, even simple cysts like the periradicular cyst derived fromrests of Malassez must possess some mitotic activation, or growth wouldbe impossible. Activation is thought to occur as a result of inammatoryproduction within the periodontal membrane.13,38 In the skin andgingiva it has been shown that inammation leads to release of inhibi-tors, which then allow the renewal of mitotic activity.15 Once a solidepithelial sphere has been formed, it is thought that it eventually out-grows its vascular nourishment and the central area degenerates to forma lumen.15,16 Following the formation of the central lumen, transepi-thelial ow of uid is sustained by osmotic forces. Thus hydrostaticpressure plays a role in the development of the classic unilocular appear-ance of most cysts. How the pressure results to produce osteoclasticresorption is less clear.17,39-41

Cysts that are derived from the more neoplastic dental lamina, orare in themselves cystic neoplasms, probably occur as a result of self-sustained or unregulated mitotic activity.42 Even in neoplastic cysts,luminal expansion may occur through degenerative effects, debris accu-mulation, and hydraulic and mitotic activity.43-45

Periapical Cyst (Radicular Cyst, Periradicular Cyst)The periapical cyst must be associated with a nonvital tooth. The toothmay be rendered nonvital by trauma, caries, or periodontal space exten-sion. As such, these cysts may be seen at any age, although permanentteeth are more likely to be involved than deciduous teeth.46 They arethought to be derived from rests of Malassez.


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cyst is essentially a subtype of dentigerous cyst that is conned just bythe overlying alveolar mucosa. Dentigerous cysts form when uid accu-mulates between reduced enamel epithelium and tooth crown.14 Asalluded to earlier, the accumulation of uid may be partially or largelysurrounded by connective tissue and epithelium.54,55 Because the thirdmolars 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 beinherent differences in impacted tooth development and how thereduced enamel epithelium is transformed/resorbed.56 They are gener-ally found in the teenage years and early adulthood.57 However, thelonger a tooth is impacted, the greater the chance a dentigerous cyst

will develop.58

to resolve, their presence should not result in a diagnosis of osteomy-elitis. Such colonies are more commonly an incidental rather than asignicant nding. 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). Enucleationis often accomplished at the time of tooth extraction. Uncountednumbers of these cysts are probably adequately resolved with endodon-tic therapy. If a radiolucency persists longer than 6 months followingendodontic therapy, enucleation and histopathologic review arenecessary.48-50

Lateralized Radicular Cyst (Lateral Radicular Cyst,Lateral Periapical Cyst)This cyst is simply a variant of the periapical cyst. It is associated witha nonvital tooth, but instead of being at the apex of the tooth the cystis located lateral to the tooth root(s). This happens because the root

canal system of teeth sometimes has exits on the lateral aspect of theroot, not just at the apex. Therefore if the path of least resistance is outone of these lateral canals the lesion will be present laterally. Otherwise,the clinical, microscopic, radiographic, and histologic features are iden-tical to the periapical cyst.

Residual CystThe majority of these cysts will be the result of leaving a periapical cystbehind following tooth extraction. All of these cysts are inammatorycysts. Occasionally an inamed dentigerous cyst is incompletelyremoved and could also be the source of a residual cyst. The clinical,microscopic, radiographic, and histologic features are identical to theperiapical cyst.48,49,51,52

Inammatory Collateral CystThis 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 includedhere. This lesion is associated with periodontal disease of a vital tooth.Uncommonly, a deep intrabony periodontal pocket may be sufcientlyisolated to allow for hydraulic expansion of the bone (Fig. 93-4). Assuch, radiographically there will be a radiolucent periradicular lesion(Fig. 93-5). There will also be a periodontal pocket associated with thatradiolucency. This diagnosis should be limited to those cases where theclinician indicates the diagnosis as the most likely choice. Otherwise,the clinical, microscopic, radiographic, and histologic features are iden-tical to the periapical cyst.53

Dentigerous Cyst (Follicular Cyst)The dentigerous cyst by denition must be associated with the crownof an unerupted tooth, developing tooth, or odontoma. The eruption

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

enucleation.

Figure 93-4. Intraoperative photograph of an inammatory collateral

cyst. Tooth is vital with periodontal pocket leading to intrabony cystic

area.

Figure 93-5. Radiograph of inammatory collateral cyst.


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or permanent teeth, but the majority of lesions are seen in the rstdecade.68 The lesion will present as a soft tissue swelling of the alveolarridge overlying an area of age-appropriate tooth development. Someeruption cysts will have a slightly blue hue color, though the normalcoral pink color of the surrounding mucosa is common (Fig. 93-8).Unlike dentigerous cysts, it is not uncommon for an eruption cyst tobe associated with deciduous teeth. Eruption cysts may be seen innewborns with an incidence of 2 per 1000 births reported.69 Clinicalfollow-up may also serve to conrm the diagnosis because thetooth will erupt within several weeks to months through the cysticexpansion.70-74

Treatment

The eruption cyst almost always resolves without intervention. Inuncommon cases eruption of the underlying tooth may be impeded ordelayed. In such cases a deroong will allow eruption.

Paradental CystThe paradental cyst is considered by some to be a variant of the den-tigerous cyst. This is because the various forms of paradental cyst alloriginate from the cementoenamel junction just like the dentigerouscyst. However, the paradental cysts are almost uniformly inamed, sothey are generally classied as inammatory cysts rather than as devel-opmental cysts. Paradental cysts occur on the buccal or distal aspect of

Figure 93-7. Clinical photograph of device used for cyst decompres-

sion. 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.

Figure 93-8. Clinical photograph of maxillary eruption cyst found inci-

dentally in an infant.


A dentigerous cyst presents as a unilocular radiolucency, which is asso-

ciated with an unerupted tooth (Fig. 93-6). Dentigerous cysts may alsoinvolve odontomas that, by nature, also have tooth crowns. Theradiolucency is generally well demarcated and well corticated. Theborder may become sclerotic or display rarifying osteitis if secondaryinfection is present. Even large cysts that have pushed the associatedtooth considerable distances will display evidence of origin from thecementoenamel junction if the lm angle is adequate. In large lesionsthe origin from the cementoenamel junction is best visualized as anarea of cortication at the cementoenamel junction. There is consider-able overlap between the appearance of small dentigerous cysts andhyperplastic follicles.56


The specimen will present primarily as variably dense brocollagenousconnective tissue with some areas being loose and myxomatous. Odon-

togenic epithelial rests are usually scattered within the connective tissueand are most common near the epithelial lining. The luminal liningconsists of nonkeratinized stratied squamous epithelium. The pres-ence of mucous prosoplasia within the lumen is not uncommon. Careshould be taken to not overinterpret the mucus prosoplasia. Cholesterolslits and their associated multinucleated giant cells may be present ininamed cysts and are generally associated with the connective tissue

wall.47 As mentioned earlier, the lumen may be partially or mostly linedby connective tissue.14 If present in the specimen, crevicular epitheliummay make microscopic separation of an inamed dentigerous cyst frompericoronitis impossible. Thus proper diagnosis requires radiographicor clinical corroboration.

Neoplastic Potential

Dentigerous cysts appear to retain the ability to transform into trueneoplasms. One study reported that 17% of ameloblastomas wereassociated with an existing dentigerous cyst.59 This gure varies bystudy, however.60-62 Both squamous cell carcinomas and mucoepider-moid carcinomas have been reported.63-67

Treatment

Dentigerous cysts are usually easily enucleated at the time of toothextraction. In large lesions decompression with subsequent enucleationmay be appropriate (Fig. 93-7).

Eruption CystThe eruption cyst is a form of dentigerous cyst that is found in the softtissue overlying an erupting tooth. Because by denition it must beassociated with an erupting tooth, eruption cysts occur only during theages of tooth development.7 They may be seen with erupting deciduous

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

molar crown.


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an erupted mandibular molar. Though the mesial aspect of a man-dibular tooth may rarely be involved, there have been no reportedoccurrences to the lingual. Craig75 reported the occasional presence ofdevelopmental enamel projections near the furcation of some teeth.This is particularly true of the subcomponent of paradental cysts knownas infected buccal bifurcation cysts. How big a role these projections playin pathogenesis remains debatable.76-81 In one series the paradental cystaccounted for 3% of all odontogenic cysts.82


The lesion will present as a well-dened radiolucency associated withbut not surrounding the coronal area of a partially erupted tooth.81

Odontogenic Cyst of Undetermined OriginIt is with great regret that another diagnosis is added to the list ofodontogenic cysts, but there appears to be no good alternative. Onoccasion the clinician and pathologist may come upon a lesion thatis not classiable by histologic, radiographic, or clinical features. Asmentioned earlier, several odontogenic cysts have identical micro-scopic features. Odontogenic cysts with identical or potentially identi-cal histologic features are referred to as the common odontogenic cysts.These common cysts are separated on the basis of clinical featuresalone.

The problem in diagnosis comes when a cyst is not associated withthe crown of a tooth, residually or with the root of a nonvital tooth.

Additionally, the cyst is not consistent with a ssural cyst but is at leastpartially located in the alveolar process. Historically, any cyst thatoccurred in an area where a tooth should have developed, or wheresupernumerary teeth could occur, were originally called primordialcysts.83 This term was used to allude to development from the toothprimordium. Unfortunately, this was proposed in 1945 before deline-ation of the features dening the OKC and a large percentage of theseprimordial cysts had features of what would now be diagnosed as anOKC. When the OKC was dened in the 1950s, some pathologistshad already recognized those histologic features in what they termedprimordial cysts and thus they began to use the term interchangeably

with OKCs. International journals, especially, came to use the termprimordial cystas a synonym of the OKC.45,84 Americans often avoidedthe term primordialor left the moniker of primordial cyst for thoselesions without features of a keratocyst.

The term primordial cyst is avoided to eliminate any confusionbetween the histopathologist and the clinician. This is intended toensure that aggressive treatment of an OKC is notperformed for thisinnocuous lesion.

Denition of the Odontogenic Cyst of Undetermined OriginAn odontogenic cyst of undetermined origin is a unilocular radiolucentcyst of the jaws with histologic features of common odontogenic cystsbut lacking the clinical, histologic, and radiographic features of anydened common odontogenic cyst (Fig. 93-9).

Lateral Periodontal CystThese cysts are thought to be derived from the dental lamina and arethus thought to retain some limited neoplastic growth potential. Thislimited neoplastic potential is best displayed by the associated lesionknown as a botryoid odontogenic cyst. Lateral periodontal cysts arelocated on the lateral surface of a vital tooth.85,86 This assumes that thetooth has not been rendered nonvital by dental caries or trauma unre-lated to cyst formation. The most common location is the mandibularpremolar/canine area. If present in the maxilla, the lateral incisor areais the most common location. However, the lateral periodontal cystmay be seen in any area of the alveolar processes. This cyst is seen inthe interproximal area between tooth roots and is usually an incidentalradiographic nding.87,88 Demographically the cyst is most common inmales by a 2 : 1 ratio with a peak incidence in the fth and sixthdecades.89 The gingival cyst of the adult and the botryoid odontogeniccysts are essentially subtypes of lateral periodontal cysts. Other cysts,especially the OKC, odontogenic cyst of undetermined origin, and thelateralized periapical cyst, also present interproximally. Histopathologicfeatures and tooth vitality are important diagnostic considerations to

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

origin.

separate these lesions. All of these lesions can be separated histologicallyand the lateralized periradicular cyst will be associated with a nonvitaltooth.


The lesion presents as a unilocular radiolucency of the alveolus that isusually well corticated. Larger lesions may result in diverged roots.90Multilocular lesions are a special subset and are classied as botryoidodontogenic cysts (see Botryoid Odontogenic Cyst later).27


The cyst lining is composed of nonkeratinized simple to stratiedsquamous epithelium. The lining is most notable for being only a fewcells in thickness (Fig. 93-10). Intermixed within this otherwise thinepithelial lining are nodular epithelial thickenings or plaques. Theplaques may display somewhat whorled epithelial cell aggregates. Thecentral cells in the aggregate may display cytoplasmic clearing. The clear

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

the lateral periodontal cyst.


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differentiated by location. The gingival cyst of the newborn is a soft tissuecyst and does not have an intrabony component (Fig. 93-11).97


These cysts should generally never appear for pathologic review.

Treatment

These cysts almost always spontaneously rupture and requireno therapywhatsoever. Occasionally a cyst will be large enough to interfere withnursing or persist to 6 or more months of age. In these rare cases, simpleenucleation or even deroong is sufcient.

Keratinizing Odontogenic Cyst (OrthokeratinizingOdontogenic Cyst, OrthokeratinizingOdontogenic Keratocyst)Recognition of the keratinizing odontogenic cyst is a rather recentphenomenon. When the OKC was rst dened, the denition did not

separate these lesions. Over time several reviewers noted and separatedkeratinizing cysts that did not seem to otherwise conform with themicroscopic criteria of the OKC.98-100 The most notable difference inthese cysts was the presence of orthokeratin rather than parakeratin,though other features such as lack of tombstoning, corrugation, andhyperchromatism are more important criteria. Wright101 was the rstto formally separate this group of cysts and proposed the name of OKC,orthokeratinizing variant. He noted the different histopathologic fea-tures and ably reported the lack of recurrences associated with theseorthokeratinized cysts. However, the nomenclature of including theterm keratocysthas created quite a bit of confusion, at least anecdotally.Historically, older texts and articles described keratinization of variousodontogenic cysts and recognized the difference of these cysts fromOKCs.47,100

The designation as orthokeratinized OKC(OKC, orthokeratinizedvariant) has evolved since rst being described. Current nomenclaturehas evolved to avoid confusion with the standard OKC. It is also

worth noting that some OKCs can contain orthokeratin, and the orig-inal series of orthokeratinizing OKCs described by Wright included7 of 60 cysts with parakeratin.101 Thus classication based solely on thetype of keratin alone is unwise.

The separation of the keratinizing odontogenic cyst is clinicallyimportant because the reported recurrence rate of the keratinizingodontogenic cyst is only 2%. The peak incidence of keratinizing odon-togenic cysts is in the third, fourth, and fth decades, with about threefourths of them being in a dentigerous cyst relationship. Other loca-tions are possible, in various relationships to the teeth. Most cysts areasymptomatic, though pain and swelling was reported respectively in22% and 13% of cases.98,99 The keratinizing odontogenic cyst is notassociated with basal cell nevus syndrome (Gorlin-Goltz syndrome).

cells contain glycogen, which can be digested with diastase. Scatteredmucous cells may be seen in some lesions but should not be a dominantfeature.90,91 The diagnosis of lateral periodontal cyst must be reservedfor lesions displaying the thin epithelium described earlier. The plaque-like thickenings are helpful microscopic features but are not alwaysfound. The connective tissue wall may contain dental lamina rests, butthey 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 nothave been evident radiographically. If multilocularity is present, thelesion is probably a botryoid odontogenic cyst. In such cases light curet-tage of the surrounding bone wall is advised. Recurrence of the simplelateral periodontal cyst is not a problem and even the recurrences ofbotryoid cysts are usually easy to manage.

Botryoid Odontogenic CystThe botryoid odontogenic cyst will usually present as a multilocularlesion and is a special variant of the lateral periodontal cyst. Botryoidrefers to the fact that these lesions may appear like grapelike clusters,both histologically and usually radiographically as well.23,25,27


Radiographically the botryoid odontogenic cyst presents in the same

preferred alveolar process locations as the lateral periodontal cyst. Smalllocules may not be seen on radiographs.23

Treatment

Like the lateral periodontal cyst, t reatment consists of enucleation withbony curettage. The multilocular nature may make this difcult, espe-cially if teeth are to be spared. With full enucleation, light bone curet-tage recurrence should be uncommon. The slow growth of these lesionssuggests that a 10-year radiographics is reasonable, though the smallsample size makes this a suggestion at best.

Gingival Cyst of the Adult

Clinical Features

This lesion is essentially the soft tissue equivalent of the lateral perio-

dontal cyst. As with the lateral periodontal cyst, it derives from dentallamina or rests of Serres.92-94 These lesions generally present as anasymptomatic bluish nodule on the facial aspect of the gingiva. Thesessile elevation will be centered in the attached gingiva, though exten-sion below the mucogingival line is possible. Unlike the lateral perio-dontal cyst, there may be a slightly increased incidence in women.95The mandibular gingiva is most commonly involved and the peakincidence occurs in the fth and sixth decades.9,96 Other odontogeniccysts may also occur in the gingiva. Histologically distinctive odon-togenic cysts that are appropriately diagnosed histopathologicallyshould not be descriptively calledgingival cysts. The possibility of somecysts of the gingivae arising from traumatically implanted surface epi-thelium does exist. Whether it is best to call these histologically differ-ent cysts epithelial inclusion cysts is debatable.95 The term gingival cystof the adultmust be reserved for those lesions with histologically distinctmicroscopic criteria.


The lesion may sometimes display supercial cupping of the corticalbone. 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 generallyonly a few millimeters in diameter and seen only in the rst few monthsof life. Though studies are appropriately devoid of histologic samplingdata, some clinical reports estimate these cysts occur in up to 50% of allnewborns. The cysts are sessile and vary from normal in color to yellow or

white. Similar-appearing inclusion cysts of the palatal midline (Epsteinspearls) or at the junction of the hard and soft palates (Bohns nodules) are

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.


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The cyst presents as a well-dened unilocular radiolucency with theborder generally being well corticated. If it is in a dentigerous cystposition, a cyst may be large (Fig. 93-12).


The epithelial lining will most often be thin with keratinization.

However, the thickness will be somewhat variable. Keratin productionvaries and may only occur on a portion of the cyst wall. Orthokeratinis characteristic but notpathognomonic.102 Most notable are the fea-tures that are not present. The features dening an OKC are absent.

Glandular Odontogenic Cyst (Sialo-odontogenic Cyst)

Clinical Features

Controversy encompasses this lesion and undoubtedly further delinea-tion of features will evolve. The glandular odontogenic cyst is usuallyasymptomatic and involves the mandible more often than themaxilla.29,103 Large cysts may be destructive and expansile.104,105 Theglandular odontogenic cyst involves adults and its pathogenesis is notyet understood.106 This cyst may be either multilocular or unilocular.The cyst is generally well dened and often well corticated.


The lesion is radiolucent and may be unilocular, but it is more com-monly multilocular. The radiographic margins are well dened andusually display a sclerotic rim.107


This cyst is lined by cuboidal epithelium of varying thickness, whichmay display cilia. Unfortunately, separating this particular microscopicfeature from normal (and insignicant) mucus prosoplasia is some-times difcult. The following features are more important in establish-ing the diagnosis. The cyst lining will be mucicarmine positive. Themucin detected by mucicarmine collects in small pools. Characteristi-cally there are cuboidal cells near the surface, which give a slightlypapillary appearance to the lumen.103 The epithelium will also containspheroid aggregates of cells.108,109 The presence of mucous cells in otherodontogenic cysts is notdiagnostic for this lesion. This lesion, in thisauthors opinion, is overcalled and second opinion is often necessary.Standard common odontogenic cysts with mucus prosoplasia areoften upgraded to glandular odontogenic cysts (Fig. 93-13). Glandu-lar odontogenic cysts may be upgraded to central mucoepidermoidcarcinoma. Great care to properly designate these lesions is necessaryto ensure proper patient care.

Treatment

Recurrence after enucleation has been reported.103 As in any multi-locular lesion, nucleation and curettage of bone is recommended. Fewcases are available to draw further treatment conclusions, but the overallprognosis is good.30 Suggestions to treat this cyst aggressively appear tobe misguided.

Figure 93-12. Radiograph associated with crown of impacted man-

dibular canine. Note that the tooth is the left canine, which has trans-

located across the arch.

Figure 93-13. Photomicrograph showing mucus cells and spherical

aggregate of glandular cells. Note: A single focus of such changes is

not sufcient to make the diagnosis of glandular odontogenic cyst.

Odontogenic Keratocyst (Parakeratinizing OdontogenicKeratocyst, Keratocystic Odontogenic Tumor)

The OKC remains an enigma for the clinician and researcher, althoughknowledge gains in recent years have allowed for an improved under-standing of this interesting lesion. The lesion was rst described byPhilipsen in 1956, but even 5 decades later the debate continues overthe pathogenesis, behavior, treatment, and classication of this cysticneoplasm.18-20 One major dilemma is whether to classify it as a cyst ora neoplasm. The current World Health Organization (WHO) nomen-clature stresses the neoplastic nature and uses the term keratocysticodontogenic tumor.

Soft tissue extension, extension into adjacent bones, and expan-sion with associated bony destruction have been reported. These reportshave prompted clinicians to question what the most appropriatemethod of treatment really is. Scharfferter and colleagues110 docu-mented increased mitotic activity within the epithelial lining of theOKC, which seems to support its neoplastic nature.

OKCs occur over a large age range. Lesions are often found duringand slightly after odontogenesis of the permanent teeth. Peak incidenceis in the second and third decades but may occur at any age. Themandible is more often involved than the maxilla, but treatment ofmaxillary lesions is often more problematic. OKCs are most commonin the mandibular third molar area, but any area of the jaw may beinvolved. Patients are often symptomatic with swelling, pain, trismus,sensory decits, and infection being the most common complaints.However, the lesion may also present as an incidental radiographicnding.

Of particular interest to the clinician is the biologic behavior ofthe OKC. Recurrence rates of up to 62.5% have been reported withenucleation alone. However, modern reports have a much lower recur-rence rate when enucleation and careful curettage are performed. Mostmodern recurrence rates are less than 10%.111,112 Reasons to explain therecurrence rate include daughter or satellite cyst formation113; incom-plete removal of the epithelial lining, leaving satellite cysts left behind;collagenase activity of the cyst114; dental lamina rests left in the cyst wallor overlying mucosa; prostaglandin-induced bone resorption115; andincreased mitotic activity. A handful of articles have demonstrated thatthe OKC can proliferate within muscle, and death from intracranialextension of mandibular OKCs has been reported by Jackson and col-leagues.84,116,117 Though these case reports should be remembered, theneed to aggressively treat allOKCs should be resisted.


OKCs may be unilocular or multilocular, multiple, or single. OKCswith calcications within a cyst wall have been reported, but calcica-tion is rare and OKCs are considered radiolucent lesions. OKCs arehighly variable in size (Fig. 93-14). They can appear pericoronally,


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periradicularly, interradicularly, apically, and even peripherally. Insummary, OKCs may occur in all areas of odontogenesis and they mayextend signicant distances.97 The borders are well dened and oftencorticated.98,118 Patients involved with Gorlin syndrome are more likelyto present with metachronous or synchronous cysts. CT scans may behelpful in assessing large lesions and CTs are often essential in assessingmaxillary lesions.119-121


The OKC has a specic microscopic appearance and the mere presenceof a keratin lining or keratin within the cyst lumen is not sufcient toassure a diagnosis of OKC. The other features unique to the OKC mustalso be seen. The stratied squamous epithelium is generally 4 to 10cells thick. The basal cell nuclei are particularly hyperchromatic, buteven the parabasalar cells are more hyperchromatic than the spinous

cells seen in other odontogenic cysts. The basal layer consists of cuboi-dal to columnar cells with a palisaded or tombstone appearance.Corrugated surface changes are often seen at the surface. Of perhapsleast diagnostic help is the nding that OKCs are surfaced by para-keratinizing stratied squamous epithelium. Again, parakeratin is notpathognomonic for an OKC.

Treatment

A handful of reports with signicant complications have led some clini-cians to perform aggressive surgical procedures on all lesions. Debatepersists about how to best manage OKC lesions in general. Treatmentshould center on decreasing the recurrence rate to a rate expected ofthe modern era and one that reduces patient morbidity. The reader isreferred to other articles. After reading many treatises, the following ismy opinion.111,112,122-130

Close radiographic follow-up is perhaps the most importantmodality to prevent complications secondary to recurrence. Recur-rences, which often occur in the rst 5 years, can take many years topresent. Recently at this institution, my colleagues and I saw a recur-rence 40 years after initial treatment, though the possibility of a newoccurrence could not be eliminated. Establishing a diagnosis is impor-tant. Adequate material must be sent to be histologically diagnosed.Common problems are that the inner layer of keratin within thelumen is sampled and the diagnostic lining and wall are not submitted.

Additionally, the diagnostic histologic features can be lost when inam-mation is present.

If the patient has more than one cyst, the possibility of basal cellnevus syndrome is elevated. All cysts should still be examined his-topathologically to conrm diagnosis. Clinical work-up to assess forsyndrome is always prudent when multiple concurrent or sequential

OKCs are diagnosed. Even when OKCs are in teenagers or youngerpatients are diagnosed with a single lesion, at least a cursory familyhistory and gross clinical assessment for the syndrome should be per-formed. Some investigators have claimed good success with decompres-sion and subsequent enucleation, while others advocate enucleation,excision of overlying mucosa, peripheral osteotomy, and chemicalcurettage.125,129

The use of Carnoys solution is controversial. Carnoy rst reporteduse of his xative for the study of nematodes in 1887.131 His goal wasto x the tissue and preserve nuclear detail for microscopic examina-

tion. However, xation of the tissue intraoperatively for future micro-scopic exam is not really the effect that surgeons desire. Surgeons desirethe chemical cauterization effect that the solution produces.

Regardless of the technique, the cyst lining must be entirelyremoved including satellite cysts and dental lamina rests. Thus carefulenucleation is followed by some bone removal. Generally this is removalof daughter cysts and rests accomplished through curettage, peripheralostectomy with rotary bur, or excision of one anatomic boundary suchas periosteum (when bone penetration has occurred).

Recurrent OKCs may need to be treated more aggressively thanprimary lesions, but in syndrome patients recurrences should beconsidered new occurrences rather than recurrences. Large lesions mayleave no other option than resection. However, one should considerdecompression to shrink the lesion, followed by enucleation and curet-tage. In this manner a discontinuity defect or damage to vital structures

is reduced or eliminated. If cortical perforation is encountered, frozensections to assess margins may be necessary. Regardless, patients mustbe followed on a regular basis for many years following treatment ofan OKC. As with most odontogenic lesions, surgery should be dictatedby the destruction already caused by the lesion at hand, rather thansimply on the histologic diagnosis.

Basal Cell Nevus Syndrome (Gorlin Syndrome, Gorlin-GoltzSyndrome, Nevoid Basal Cell Carcinoma Syndrome)This complex syndrome is called by many names, and the nomencla-ture often depends on what portions of the syndrome (e.g., bid ribs,OKC) are present. In the Gorlin and colleagues132-134 description, nofewer than 37 anomalies have been associated with this syndrome. Thereader is referred to the original sources.

OKCs are often the rst diagnosis of the syndrome to present in

childhood and often aid in establishing a diagnosis. This is especiallytrue in cases in which there are new mutations with no prior familialhistory.135 Up to 40% of cases may be new mutations, though genetictesting is advancing and there may be large variations in expression inthis autosomal dominant disease.134 One patients rst cyst occurred inthe seventh decade. For this reason the syndrome should not be ruledout even in a middle-aged patient, and family history and phenotypemay help in all age groups.

Treatment

The key to management of these patients is to at least phenotypicallyevaluate any patient that has an OKC for the syndrome. The assessmentmay be as simple as screening the patient for clinical evidence of anyanomalies. In syndromic patients, recurrences should be presumednew occurrences rather than recurrences. Decompression is highlydesirable in large lesions, and teeth should generally be saved ratherthan extracted if possible. Undoubtedly some teeth will need to beremoved for access, but canines, incisors, and rst molars should beheavily favored for retention. Each case is highly variable. As a medicaladvisor for this syndromes support group I invite all providers tocontact www.bccns.org for information.

Calcifying Odontogenic Cyst (Gorlin Cyst)The calcifying odontogenic cyst (COC) is an unusual odontogeniclesion. As with the OKC, experts debate whether to classify the COCas a cyst or neoplasm. In this chapter the primarily cystic lesion withghost cells is considered rst, and the more solid epithelial odontogenicghost cell tumor is considered later. The cyst was described by Gorlinand colleagues136,137 in 1962. It is worthy of delineation because of itsunusual clinical and histopathologic features. The COC occurs both

Figure 93-14. Radiograph of odontogenic keratocyst with bowing of

inferior border and scalloping.


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Treatment

Treatment of the COC is simple enucleation of unilocular lesions. Asin any multilocular lesion, enucleation with bony curettage is adequatetherapy for the central lesions. The peripheral lesions require simpleexcision.143 Recurrence is not expected, though radiographic follow-upis prudent.

Conclusion, Odontogenic CystsThis 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 involv-ing the jaws can be treated adequately with enucleation with or withoutcurettage. In general multilocular cyst or cysts with scalloped bordersneed enucleation with bony curettage. Unilocular cysts can be simplyenucleated. However, some cysts such as the OKC or certain variantsof the calcifying odontogenic cyst, due to their neoplastic nature, mayrequire additional surgical treatment, with enucleation and bony curet-tage advisable in all lesions. As stressed repeatedly, the treatment is oftendictated more by the behavior (destruction the lesion has alreadycaused) than by the histologic diagnosis.

Malignant Odontogenic Tumors andMalignancies Arising in Odontogenic

Cysts or TumorsMalignant transformation of odontogenic cysts is fortunately a rareoccurrence but nonetheless occurs.144-146 Many malignant transforma-tions are considered to arise from residual cysts and occur in an eden-tulous area.147,148 Transformation from an associated dentigerous cystis seen in 25% of the reported cases.146 Some OKCs have shown dys-plastic features with few actually undergoing malignant transforma-tion.149,150 In summary, any cyst can undergo malignant transformationbut such lesions are rare. Malignant lesions are likely to present withpain and swelling, but dysthesia is a foreboding symptom. Gardnerreviewed the literature from 1889 to 1967 and found 25 acceptableexamples of carcinoma arising from an odontogenic cyst.151 AMEDLINE search for this chapter yields more than 100 additionalexamples.

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 cen-trally in the jaw and the possibility of entrapped salivary tissue cannotbe totally excluded. Bruner and Batsakis153,155-157 reviewed a total of 66reported cases of central mucoepidermoid carcinomas of the jaws,

which indicates they may be more commonly reported than centralsquamous cell carcinoma malignancies.

Elzay156 offered a classication for primary intraosseous carcino-mas of the jaw in 1982. A scheme of classication is offered in Box93-2 with modications from that of Elzay to allow for salivary malig-nancies (especially mucoepidermoid carcinomas), origin from odon-togenic tumors (other than ameloblastoma), and inclusion of sarcomas.

Verifying carcinomas arising de novo is difcult, but de novocancers may be assumed if conned to intra-alveolar bone without asoft tissue component. Cysts appear to be a more common site of originthan odontogenic tumors. But nearly all odontogenic tumors have beenreported to have malignant counterparts. The age at occurrence is inthe sixth or seventh decade with some reports of a 2 : 1 male predomi-nance, but full-ranging reviews are lacking.157 And even if such reviews

were available for all lesions seen in Box 93-2, their wildly variablecharacters would most likely be as appropriate as comparing apples withoranges.

Microscopic FeaturesAll malignant lesions are based on histopathologic criteria.

TreatmentSignicant treatment and prognostic differences exist between centralsquamous cell lesions and central mucoepidermoid lesions.158 Treat-ment is based on size, histologic type, and histologic grade.

within the bone and peripherally in the gingiva. COCs are often asso-ciated with odontomas or active products of odontogenesis.138

The separation of the cystic lesions from the solid lesions is appro-priate. The solid/neoplastic version is considered briey in the odon-togenic tumor section under epithelial odontogenic ghost cell tumor.139The occurrence of the COC compared with the epithelial odontogenicghost cell tumor may approach 40 : 1. Subclassication of the cysts ismore of a histologic exercise than of prognostic or therapeutic impor-tance. The reader is directed to articles by Praetorius and colleaguesand Hong and colleagues for subclassication schemata.140,141

The origin of the COC is probably the early dental lamina. Thismay be best supported by the fact that craniopharyngiomas of the

pituitary region often mimic the COC. COCs occur over a large agerange. Though the mean age at occurrence is in the fourth decade, thepeak incidence is in the second and third decades. Lesions in youngadults are often associated with odontomas. The anterior portion of the

jaws is more commonly involved than posterior regions, though anyarea can be involved. There is essentially equal distribution betweenfemales and males when all types are considered. There may be a slightmaxillary predominance over the mandible.139 Peripheral COCs will becentered in the attached gingiva.


The radiographic appearance is highly variable. As with the OKC, itmay be either unilocular or multilocular, though unilocular lesions aremore common. This is one of the odontogenic lesions that is classicallyconsidered to be mixed radiolucent radiopaque, though most lesionsare purely radiolucent in the absence of an associated odontoma. Ifmineralization occurs in COCs without an odontoma, the radiopacitiesare often peripherally located. This appearance has been compared tosnowdrifting.142


Ghost cells are the classic cells seen in the COC. Ghost cells are notpathognomonic of COCs. In fact, ghost cells may be seen with otherlesions such as odontomas, ameloblastic bro-odontomas, and amelo-blastomas. Of more signicance is the presence of odontogenic epithe-lium with hyperchromic nuclei and somewhat of a palisaded basilarlayer (Fig. 93-15). The thickness of the cyst wall is fairly thin andgenerally less than 10 cells thick. However, the thickness varies alongthe luminal wall and plexiform connections are often present, whichcreates a multicystic appearance in more complicated cysts.

Figure 93-15. Photomicrograph showing ghost cells, odontogenic epi-

thelium, and stellate reticulum-like areas.


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articles are reviewed it becomes clear that there is a great desire for acookie cutter type of recipe approach for every lesion based on diag-nosis alone. Unfortunately, this just is not a realistic approach and inthis authors opinion has resulted in gross overtreatment in a numberof patients. As with the odontogenic cysts, the presence of scallopingand particularly multilocularity makes curettage following enucleationnecessary. Although scalloping and multilocularity may be seen onplanar lms, intraoperatively the surgeon is in an ideal position to assessfor these features in three dimensions. If scalloping or multiple loculesare 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 dening criteria, measuring outcomes, reporting postoperative mor-bidities, and analyzing methods in relation to benign odontogenictumors. This poor stewardship is true in both arches but is especiallyproblematic when attempts are made in assigning therapeutic modali-ties indiscriminately to both the mandible and maxilla. In actuality theanatomic problems in each jaw differ dramatically and surgical differ-ences abound.

In the mandible more emphasis needs to be paid to inferior andposterior cortical bone relationships to the tumor to potentially avoiddiscontinuity resections of these benign lesions. With the exception ofameloblastoma, there are only a handful of reports of mandibularbenign odontogenic tumors getting away from the surgeon into softtissues or nearby bones. Yet a cookie cutter approach is often applied.

Ameloblastoma-like therapeutic models are applied to many benignodontogenic tumors. I am not aware of any studies on the morbiditiesassociated with nonameloblastoma recurrences in the modern world ofimaging. Likewise, despite studies associated with the jaw resectionsand obturators (generally in cancer therapy),159-168 there are no studieson quality-of-life issues associated with benign odontogenic tumortherapy. Evidence to support recommended treatment margins isusually based on comparing recurrence rate with ameloblastomas, notthe biologic behavior of the tumor. In addition, the 1-, 1.5-, and 2-cmmargins recommended are often unclear. Regarding benign odon-togenic lesions other than ameloblastomas, studies that have actuallycontrolled for conrmed resection margins, pathologically and radio-graphically before and after surgery, are terribly lacking. For amelo-blastomas 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 rec-ognize the simple fact that the actual goals are to ensure andconrmtumor removal, not to have a one-size-ts-all guideline. They alsodiscuss confusion about solid and nonunicystic cystic ameloblastomas.More discussion of this problem is provided later. Gardner does anexcellent job on the problems of doing retrospective analysis of theliterature on ameloblastomas.170

In the maxilla, 1-cm bony margins are sometimes recommendedin the proximal-distal direction. However, the anatomy of the sinuses,nasal cavity, orbit ethmoids, and pterygoid plates in many instancesmakes the use of anatomic boundaries more appropriate. In general,one or two anatomic boundaries are sufcient to ensure excision. In alllesions, even the ameloblastoma, the periosteum is thought to be aneffective tumor barrier.171 The interested lifetime/evidence-basedlearner is invited to perform a MEDLINE search of actual invasivebenign odontogenic tumors. A 4-decade review by Leibovitch and col-leagues172 found only 11 reported cases of ameloblastomas with orbitalinvolvement. A MEDLINE search for this chapter revealed about thesame amount of reports (using search terms of ameloblastoma com-bined 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 adoubt, soft tissue extension of recurrent ameloblastomas is a realproblem, with Sampson and Pogrel documenting a high percentage ofameloblastomas involving soft tissues in a series of 26 cases.173 But theameloblastoma is a special case and is covered more thoroughly later.The following section discusses general principles concerning the otherodontogenic tumors. With the exception of malignant variants, thereports of other odontogenic tumors extending, involving, or invadingother adjacent structures are extremely rare.

Odontogenic TumorsThe odontogenic tumors are a heterogeneous group of tumors that aregenerally separated in classication schemes by what components ofodontogenesis are present within the tumor. Box 93-3 shows the clas-sications used in this chapter. When reviewing the treatment of thesetumors, multiple considerations must be accounted for. When many

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 broma

Ameloblastic brosarcoma

Ameloblastic bro-odontoma

Odontoma

Complex odontoma

Compound odontoma

Odontoameloblastoma

Mesenchymal odontogenic neoplasms

Odontogenic myxoma

Cementoblastoma

Ossifying broma

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 brosarcoma

b. Fibrosarcoma

c. Myoepithelial carcinoma


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Unicystic AmeloblastomaUnicystic ameloblastomas account for approximately 15% of all amel-oblastomas. Unicystic ameloblastomas may be found in any odon-togenic tissuebearing area. Most unicystic ameloblastomas are found

in the posterior mandible. Unicystic ameloblastomas most often occurin the second and third decades, a somewhat younger population thanreported for the solid ameloblastoma. As with other odontogenic cystsand tumors, unicystic ameloblastomas are usually asymptomatic unlesssecondarily inamed.97


Unicystic ameloblastomas present as radiolucent, unilocular lesions,with well-demarcated, corticated borders, indistinguishable from mostodontogenic cysts or tumors. Many unicystic ameloblastomas appearto be dentigerous cysts both on radiographic and gross examination.However, they may be found in any location.


The microscopic features known as Vickers and Gorlin criteria denethe unicystic ameloblastoma. These features are (1) columnar basilarcells, (2) palisading of basilar cells, (3) polarization of basilar layer nucleiaway from the basement membrane, (4) hyperchromatism of basal cellnuclei in the epithelial lining, and (5) subnuclear vacuolization of thecytoplasm of the basal cells. Above the basal layer, loosely aggregatedstellate cells resembling the stratum spinosum of a developing tooth arenoted (Fig. 93-17).174 It is important to realize that some portions ofunicystic ameloblastomas may not show all these features. A variationof unicystic ameloblastoma described by Gardner allows for a plexiformvariant. Inammation may disrupt the diagnostic features of unicysticameloblastoma.175-177

As in all odontogenic cysts and tumors of the jaws, the entirespecimen needs to be embedded because the treatment depends on thepresence or absence of ameloblastomatous epithelium in the brous

wall.

In assessing the benign odontogenic tumors, it is essential tocritically read reports on how margin measurements were dened andhow those margin measurements were conrmed both intraoperativelyand postoperatively. I know of no adequately described prospectivereport. For example, I believe such measurements are in relation to themedullary bone and do not necessarily imply cortical bone. Surgicallyand restoratively, the loss of thin cortical bone on the buccal, lingual,and alveolar aspects is different from losing the inferior border of themandibular body, the posterior border of the ascending ramus, or for

that matter the condylar head or condylar neck. In all cases, it is thisauthors plea to always ask rst, Is there any realistic chance of thismandibular benign tumor getting away from me, if it recurs? Second,ask, Has the tumor already destroyed any of the critical structuralelements of the mandible? Third, ask, Is there a reasonable chance ofradiographic and patient follow-up? I believe the rst question willresult in the surgeon realizing that loss of critical bony structures isunnecessary in most cases and the cookie cutter approach can be mod-ied for the patient at hand. In the second question, if the lesion hasnot already destroyed critical structures, there are probable criteria notto iatrogenically destroy them. A huge caveat to this is that the lesionmust be far enough away from these important structural elements toallow for a radiographically clear margin on the resected specimen. Theclear margin will also then need to be conrmed histopathologically. Ifcritical structures have already been destroyed by the lesion, the surgi-cal decisions are straightforward. In the third question there are prob-ably 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 ofa recurrence alone. There are no reports of recurrence rates droppingto 0% after segmental resection. The surgeon is urged to review theliterature with an eye to evidence-based data.

The maxillary lesions are more problematic due to the short dis-tance needed to involve areas difcult to operate in and oblate thetumor. Such areas include but are not limited to the pterygoid plates,orbital oor, and pterygopalatine ssure. The head and neck surgeonrealizes that in some areas any benign tumor is difcult to access andcompletely remove. Thus persistence of tumors in these areas is morea problem of location than of the inherent invasive potential of thetumor. Carlson and Marx169 do a good job of discussing biologic bar-riers in their article.

Figure 93-16. Intraoperative radiograph. Note that the posterior

margin is closer than the desired 1-cm margin. Such intraoperativeradiographs help obviate the inability to perform frozen sections on

bony tissue.

Figure 93-17. Photomicrograph of unicystic ameloblastoma with

typical ameloblastomatous changes.


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(how they conrm three dimensionally how a single cyst can makemultiple locules and remain unicystic has never been adequatelyexplained in my opinion). However, in my review of the literature,multilocularity increases the chance of recurrence and multilocularlesions should be at least enucleated and curetted rather than just enu-cleated. In my institution, multilocular and multicystic lesions wouldbe signed out simply as ameloblastoma and presumed to be treated assuch. Unilocular lesions may be histologically multicystic. Multicysticlesions are notunicystic lesions, so they should be considered standardameloblastomas and treated as such.

In their review of 193 unicystic ameloblastomas, Philipsen andReichert182 found wide variations in denitions, nomenclature, and

what lesions were included under the heading unicystic ameloblast-oma. Simply put, the literature is horrible. Even separation of termssuch as luminal, intraluminal, and mural varies among authors.

As proposed originally by Robinson and Martinez,178 the reasonfor the diagnosis of unicystic ameloblastoma was to separate a prog-nostically distinct entity. Even in their report, Robinson and Martinezhad a recurrence rate of about 20%. But they allowed for connectivetissue nests, multilocularity, and large cysts. Two of their three lesionsdescribed as large dentigerous cysts recurred. Eversole and col-leagues184 later used 2 cm as a cutoff for size because they found thatlarger cystogenic ameloblastomas had a propensity to recur withsimple enucleation. Robinson and Martinez178 did not separate lesionsby connective tissue involvement. But authors including Philipsen,

Reichart, and Ackerman and colleagues (in various publications) haveshown that connective tissue involvement is an important predictor ofrecurrence with simple enucleation. They designate these as what theycall type 3 unicystic ameloblastomas and state that they tend to recur(i.e., behave like standard ameloblastomas if only enucleation is per-formed). Current wisdom is that the 20% recurrence rate of Robinsonand Martinez may have been due to large size or connective tissueproliferations.

Needless to say, inconsistencies have led to confusion. A goal ofthis chapter is to emphasize that the reason for the unicystic designationis to use the minimal amount of surgical intervention while minimizingthe chance of recurrence. The literature is fairly clear that a subset ofunicystic ameloblastomas can be managed with enucleation alone (orperhaps combined with minimal bony curettage). In this analysis thesubset is the denition of unicystic ameloblastoma used.

Simple Unicystic Ameloblastoma A unicystic ameloblastoma (referred to here as a simple unicysticameloblastoma) requiring enucleation only must have the followingcharacteristics:

1. Histologic features conform to criteria established by Vickers andGorlin for the diagnosis of an ameloblastoma.

2. Radiographic evidence of a singular unilocular radiolucency exists.Denitive septation requires exclusion, so evidence of peripheralscalloping (except between tooth roots) may eliminate the possibil-ity of a lesion being considered unilocular.

3. Intraoperative conrmation of unilocularity, anymultilocular/mul-ticystic characteristic, and cortical perforation or soft tissue involve-ment preclude interpretation of the lesion as unicystic.

4. Histologic features display only luminal or intraluminal involve-ment. Proliferation of the ameloblastoma into the brous connectivetissue wall, whether plexiform or follicular, precludes diagnosis ofthe lesion as unicystic.

5. Size of the lesion must be less than 2 cm.

I can only hope that further studies continue to dene andseparate the unicystic ameloblastomas, as well as delineate the line of

when to designate a lesion as simply an ameloblastoma. Experienceis available to justify the separation, and hopefully the science willfollow.

Definitions, Clarifications, and Treatment Recommendations

A unicystic ameloblastoma must be unilocular, as well as unicystic, anddisplay the pathologic features of an ameloblastoma lining the lumenbut not invade the connective tissue (Fig. 93-18). From the beginning,

criteria have varied and caused confusion, but this denition applies inthe following discussion.

The unicystic ameloblastoma was separated from the standardameloblastoma by Robinson and Martinez in 1977.178 The subtitle ofthat seminal paper was a prognostically distinct entity. Since thattime the application of their original denition has been problematic,

with others often further muddying the picture. A number of authorshave attempted to provide evidence of predicted behavior for differenttypes of unicystic ameloblastomas.178-183

The rst premise in this chapters coverage of the unicystic amel-oblastoma is that the only reason to separate the unicystic ameloblas-toma is for therapeutic planning and expected clinical behavior. Eversince the original paper, it has been regrettable that multilocularity andconnective tissue invasion were sometimes allowed within the diagnos-tic criteria. Ackermann and colleagues183 have analyzed unicystic

ameloblastomas with connective tissue invasion as type 3. Theyfound that they often recur if only enucleation is performed as therapy.For this reason, though, they should be more thoroughly studied andmanaged like a standard ameloblastoma. And thus separation as aunicystic ameloblastoma is spurious at best. Likewise, Philipsen andReichart182 found that multicystic or multilocular cystic ameloblasto-mas recurred with simple enucleation. Again, this should make it clearthat they should not be grouped under the designation of unicysticameloblastoma. These features are seen in regular ameloblastomas,and determining where to draw the line of what is too much multi-locularity or too much connective tissue proliferations is totally subjec-tive and unwise unless future studies dene a method to separatelesions. Until such studies, unicystic ameloblastomas should be consid-ered as such only if they are unicystic and unilocular and display noconnective tissue invasion.

Some additional background information may also be helpful.Eversole and colleagues184 found recurrences more common (actuallyall four recurrences) in lesions larger than 2 cm. Unfortunately they didnot stratify their data to state whether these larger lesions were multi-locular or how the connective tissue wall was invaded.184 But this reportimplies that large or expansile lesions may recur even if the ameloblas-toma is cystic. Likewise, a review of the original paper by Vickers andGorlin,174 which dened the features of ameloblastomas, reveals that alltheir cases were recurrences of what today would have been diagnosedas unicystic ameloblastomas.

Unicystic does not mean unilocular. Some authors allow for amultilocular radiographic appearance.185 These authors often use termssuch as cysticor cystogenicinstead of unicystic. Regardless, the intent isto attempt to group these lesions with the unicystic ameloblastoma.Some purport that histologically the multilocular lesion was unicystic

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.


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layer nuclei away from the basement membrane, hyperchromatism ofbasal cell nuclei in the epithelial lining, and subnuclear vacuolizationof the cytoplasm of the basal cells. Above the basal layer, loosely aggre-gated 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 ofameloblastomas: (1) their ability to inltrate medullary bone and arelative inability to inltrate compact bone; (2) the location of thetumor. As noted earlier, tumors near vital structures such as the orbitor cranial base are much more difcult to control and pose greaterclinical problems. Free margins of excision are difcult to obtain inameloblastomas arising in the posterior maxilla. Dense compact bonesuch as that of the inferior border of the mandible or ramus acts as the

rst-line barrier.187

The outer periosteum appears to serve as a backupbarrier to prevent tumor spread, but once it is broken, access to vitalstructures may occur.171 In the maxilla, only a thin cortical plate existsbetween contiguous bones and is generally thought of as a poor barrierto prevent the spread of ameloblastomas.169 Tumors of the posteriormaxilla involving the orbit are the most difcult to treat and manage.Undoubtedly such lesions will present with unique and specic prob-lems related to the individual case.188

Simple enucleation of ameloblastomas is not considered standardcare in the United States. Even when it is combined with curettage,ameloblastomas are known to recur. Yet successful results with enu-cleation and curettage have been reported.189,190 The recurrence rate isthought to be due to the fact that ameloblastoma inltrates the trabec-ulae of cancellous bone. The reported success with curettage (or periph-eral ostectomy with rotary bur) is probably due to relatively efcient/aggressive medullary bone removal. It is generally considered a fact thattumor inltration frequently extends beyond the apparent radiographicmargin. Ensuring even amounts of bone removal with enucleation andcurettage can be difcult. Small bits of tumor may remain within thebone without the ability to assess margins grossly or histologically. Itis thought that resection with adequate margin is the most predictablemethod to assure that the tumor will not recur. A resected specimenallows for intraoperative radiographic assessment of adequate marginsand postoperative histologic conrmation of margins.

Histologically simply clear margins are acceptable. How patholo-gists deal with resected bone specimens in the pathology laboratory isinconsistent. The surgeon should explicitly request that the entirebonyspecimen be demineralized and margins fully assessed. The surgeonshould mark surfaces that are not margins such as the vestibule, gingiva,alveolar mucosa, and sinus mucosa. As a pathologist, I know how much

Ameloblastoma, Intraosseous Type*

Definition

The ameloblastoma is a neoplasm of the enamel organ that recapitulatesthe cells necessary for tooth crown development. Intraosseous amelo-blastomas arise from the lining of an odontogenic cyst, reduced enamelepithelium, or odontogenic rests. In the soft tissues of the oral cavity,specically the gingiva or alveolar mucosa, they may arise from the basal

cell layer. Those that arise from the overlying soft tissue are calledperipheral ameloblastomas and are covered separately. In this chapter thethree clinical types of ameloblastoma are unicystic ameloblastoma,peripheral ameloblastoma, and ameloblastoma. Here the modiers ofmulticystic or solid are not used. They are not separated here becausethey are treated the same. Of these three, unicystic and peripheral havea much better clinical outcome after a conservative removal and assuredmargins. For clarication, I use the term intraosseous ameloblastoma toclarify that the lesion discussed is notperipheral.

Intraosseous ameloblastomas occur in the mandible and maxillawith the mandible accounting for about 80% of all cases. In the max-illae, ameloblastomas may evolve in the maxillary sinonasal region, as

well as during the alveolar process. The location of the tumor is animportant factor in the long-term prognosis. Tumors that are in theanterior maxilla or body of the mandible or are conned to the man-

dible are less likely to cause signicant problems. Conversely, thosepenetrating the mandible in the posterior ramus region and those ofthe posterior maxilla can extend into areas difcult to manage.186

Radiographic Findings

Small ameloblastomas appear as a unilocular radiolucency with well-demarcated and at least partially corticated borders. These radiolucentlesions are indistinguishable from other cysts or benign tu

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Flint Cumming Otolaryngology CHAPTER 93 – Odontogenesis Odontogenic Cysts and Odontogenic Tumors