Histopathology 2009, 54, 401418. DOI: 10.1111/j.1365-2559.2008.03097.

REVIEW

Lesions of the jaws

P J Slootweg
Department of Pathology, Radboud University, Nijmegen Medical Centre, the Netherlands

Slootweg P J (2009) Histopathology 54, 401418

Lesions of the jaws

The jaws differ in various aspects from all other bones in the skeleton. Embryologically, they are for the major part derived from migrating cells of the cranial neural crest, the so-called ectomesenchyme, and not merely from mesoderm, and they contain teeth. This latter point, especially, results in the presence of lesions that are not found in other bones, a broad variety of odontogenic cysts and tumours. They will be the major topic of this review. Other lesions, not strictly odontogenic but also mainly conned to the jaw bones, are giant cell lesions, bro-osseous lesions, and the melanotic neuro-ectodermal tumour of infancy. They also will be included in this overview.

Keywords: cysts, bro-osseous lesions, giant cell lesions, jaw diseases, odontogenic tumours Abbreviations: WHO, World Health Organization

Embryogenesis
Teeth develop from epithelial cells from the mucosal lining of the oral cavity and cranial neural crestderived ectomesenchymal cells. The epithelial part forms the cap-shaped enamel organ consisting of an inner side of high cylindrical inner enamel epithelium that differentiates into enamel-forming ameloblasts, an external surface consisting of cuboidal outer enamel epithelium and an intervening loose epithelial structure known as stellate reticulum. The ectomesenchymal part that is enclosed by the enamel organ is known as the dental papilla: dental papilla cells at the border with the inner enamel epithelium develop into dentinforming odontoblasts. Both enamel organ and dental papilla together are surrounded by a brous capsule, the dental sac or dental follicle. As the enamel organ elongates through downward proliferation, it creates a tube that maps out the form and size of the roots of the teeth.1 Therefore, remnants of odontogenic epithelium can be found in the jaw bone
Address for correspondence: P J Slootweg, Department of Pathology, Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500HB Nijmegen, the Netherlands. e-mail: p.slootweg@pathol.umcn.nl
2008 The Author. Journal compilation 2008 Blackwell Publishing Limited.

at a level as deep as the root tips of the teeth (Figure 1A,B). Those that lie in the connective tissue that connects the tooth with the jaw, the so-called periodontal ligament, are known as rests of Malassez. Corresponding epithelial remnants in the gingiva are named rests of Serres.

Cysts of the jaws

Cysts derived from odontogenic epithelium are called odontogenic; those that originate from other epithelial structures are known as non-odontogenic. Within the odontogenic cysts, one discerns between developmental and inammatory.2 The inammatory cysts are thought to arise from inammation-induced epithelial proliferation with subsequent central liquefaction. The developmental cysts lack a clear-cut aetiology. The various entities are listed in Table 1. Unless stated specically, all cysts are cured by simple enucleation and do not show any tendency to recur. From a practical view, the radicular cyst, the dentigerous cyst and the odontogenic keratocyst are the most important, as they have the highest incidence. All other cyst types are very rare.

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Table 1. Cysts of the jaws2 a. Odontogenic cysts inammatory Radicular cyst Residual cyst Paradental cyst b. Odontogenic cysts developmental Dentigerous cyst Lateral periodontal cyst Botryoid odontogenic cyst Glandular odontogenic cyst Odontogenic keratocyst (keratocystic odontogenic tumour13) Gingival cyst c. Non-odontogenic cysts Nasopalatine duct cyst Nasolabial cyst Surgical ciliated cyst

Figure 1. A, Panoramic radiograph, showing that in childhood, the jaw is crowded by both deciduous and fully or partly developed permanent teeth. B, Detail showing one of the tooth germs together with histological details to illustrate the ubiquitous presence of epithelium in the jaw: in the dental follicle (left) and at the developing root tip with the enamel organ mimicking ameloblastoma (right). Dental papilla tissue that may be confused with myxoma lies adjacent to the enamel organ.

o d on t o g e n i c c ys t s i n f l a m m a t o r y Radicular cysts are located at the root tips of teeth in which the dental pulp is necrotic, mostly due to dental caries. Subsequent chronic inammation in the adjacent jaw area causes growth of the epithelial rests of Malassez present in that area. Subsequent central liquefaction necrosis of these enlarged epithelial rests results in formation of a cyst that is lined by nonkeratinizing squamous epithelium.3 This epithelium is usually spongiotic and inltrated by inammatory cells. Within the cyst epithelium, hyaline bodies of various sizes and shapes may be present, the so-called Rushton bodies (Figure 2).4 Occasionally, the lining squamous cells are admixed with mucous cells or ciliated cells. In terms of differential diagnosis, one should realize that an identical histology may be shown by other jaw cysts, both of the odontogenic as well as of the nonodontogenic category in particular when there are extensive inammatory changes in the cyst wall.

Figure 2. Radicular cyst lined by non-keratinizing squamous epithelium and containing many intraepithelial deposits known as Rushton bodies. These corpuscles should not be mistaken for the ghost cells characteristic of the calcifying odontogenic cyst.

Therefore, the diagnosis of a radicular cyst depends on the association of the cyst with a decayed tooth and not on the presence of characteristic histological features. When a radicular cyst is left behind in the jaw after extraction of the causative tooth, it is called a residual cyst. The last inammatory cyst to be discussed is the paradental one. This cyst is not located at the root tip, but at the lateral side of the tooth where the enamel

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cap ends and the root begins.5 Histologically, they are similar to radicular as well as residual cysts. od o n t og e n i c cy s t s de v el o p m e n t a l A dentigerous cyst surrounds the crown of a tooth that has not migrated into the oral cavity, but still lies buried in the jaw bone (Figure 3). This cyst arises through uid accumulation between tooth crown and collapsed enamel organ. Grossly and radiologically, the cyst appears as a bag in which the crown part of the embedded tooth, mostly the mandibular third molar or the maxillary canine, protrudes and forms a collar at the neck of the tooth at the border between root and crown. The cyst wall has a thin epithelial lining that ususally consists of only two to three layers of cuboidal cells. Also, mucus-producing cells as well as ciliated cells may be observed. The brous cyst wall may contain varying amounts of odontogenic epithelial islands. In case of inammation, the epithelium becomes hyperplastic and resembles the lining of a radicular cyst. In those cases, radiological features are decisive. A radicular cyst is a radiolucent lesion at the root tip of a decayed tooth; the dentigerous cyst is a radiolucent lesion surrounding the crown part of an embedded tooth. The lateral periodontal cyst is a small cavity that lies in the jaw bone between the roots of the teeth,6 not at the root tip but more close to the tooth crown, probably arising from the rests of Malassez .The neighbouring teeth are usually normal, without tooth decay or pulp necrosis as is the case with the radicular cyst. The lateral periodontal cyst is lined by a thin, non-keratinizing squamous or cuboidal epithelium with focal, plaque-like thickenings that consist of clear cells that may contain glycogen (Figure 4).7 Rarely, cysts with

Figure 4. Clear cells forming epithelial thickenings are the histological hallmark of the lateral periodontal cyst.

Figure 3. Radiograph showing smooth unilocular radiolucency in which a tooth protrudes. This histological picture is shared by dentigerous cyst, odontogenic keratocyst and unicystic ameloblastoma.

this typical epithelial lining including the plaques are large and multilocular and not only conned to the jaw bone surrounding the teeth but, in contrast, occupying major parts of the jaw bone; this variant is known as a botryoid odontogenic cyst, a lesion that may behave aggressively, as exemplied by recurrence.8 An epithelial lining containing plaques may also occur in the glandular odontogenic cyst (see next cyst to be discussed), but then as part of a much more complicated epithelial lining. So there are no real differential diagnostic alternatives for the lateral periodontal cyst and its large multilocular variant, the botryoid odontogenic cyst. Another cyst that may attain considerable size and exhibits a multilocular radiological appearance is the glandular odontogenic cyst, also called sialo-odontogenic cyst. The epithelial lining of this cyst is very complex. It is partly non-keratinizing squamous, partly cuboidal or columnar with cells that can have cilia and may form papillary projections. Focal thickenings similar to the plaques in the lateral periodontal cyst and the botryoid odontogenic cyst may also occur. Moreover, apocrine and mucus-producing cells may be present. Focally, the epithelium shows areas of increased thickness in which glandular spaces are formed (Figure 5). Moreover, the epithelial cells may form globules with a whorled centre. Recurrence may occur.9 The co-existence of mucus-producing cells and squamous cells may cause differential diagnostic problems with well-differentiated mucoepidermoid carcinoma. However, this salivary gland tumour only rarely occurs within the jaw bone and lacks the other epithelial morphologies outlined above. Very important from a clinical view is the odontogenic keratocyst. This cystic jaw lesion is mainly seen

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Figure 5. The lining of the glandular odontogenic cyst consists of different kinds of epithelium that may form glandular spaces.

Figure 6. The odontogenic keratocyst shows basal palisading and a corrugated supercial layer of parakeratin. These characteristic features are lost in areas of adjacent intramural inammation.

in the lower jaw and may involve major areas of the mandibular body: radiologically it shows a large multilocular radiolucency. This cyst may occur sporadically, but also within the context of naevoid basal cell carcinoma syndrome. Histologically, the odontogenic keratocyst shows a lining of stratied squamous epithelium with a welldened basal layer of palisading columnar or cuboidal cells and a supercial corrugated parakeratin layer. The underlying cyst wall may contain tiny daughter cysts and solid epithelial nests; they are more common in cysts associated with the naevoid basal cell carcinoma syndrome.10 When inamed, the odontogenic keratocyst lining changes into a non-keratinizing stratied epithelium exhibiting spongiosis and elongated rete pegs (Figure 6). These inammatory alterations may be so extensive that it will be impossible to make a diagnosis of odontogenic keratocyst or to make the distinction from other jaw cysts, in which specic histology may also be obscured by similar secondary alterations. Therefore, extensive additional histological sampling is required when the oral surgeon diagnoses an odontogenic keratocyst because of size and radiological appearance and the pathologist is unable to conrm this diagnosis on initial examination. Missing a diagnosis of keratocyst negatively inuences appropriate patient care, as this cyst tends to recur after enucleation and partial jaw resection is sometimes needed for cure.11,12 Because of this neoplastic behaviour, the most recent World Health Organization (WHO) classication proposes the diagnostic designation keratocystic odontogenic tumour for this lesion.13

Occasionally, intraosseous cysts are lined by orthokeratinized epithelium, thus having the appearance of an epidermoid cyst. Such cysts are known as orthokeratinized odontogenic cysts. Differentiation from the odontogenic keratocyst with parakeratinization is clinically important, as recurrence of the orthokeratinized cysts is rare.14 Gingival cysts are, as their name implies, located in the gingival tissues. They probably arise from the rests of Serres. They may exhibit keratinization. Plaques similar to those occurring in the lateral periodontal cyst may also be seen.15 Therefore, the gingival cyst may be considered the soft tissue counterpart of the lateral periodontal cyst. Gingival cysts of infants occur either single or multiple in the jaw mucosa of the newborn infant. When occurring at the midline of the palate, they are known as palatal cysts of infants. Histologically, they resemble epidermoid cysts and do not contain the epithelial plaques diagnostic of the adult-type gingival cyst mentioned above.16,17 non-odontogenic cysts The nasopalatine duct cyst is located within the nasopalatine canal that runs from nose to the oral cavity through the midline of the anterior bony palate, just posterior to the central incisor teeth. The cyst arises from epithelial remnants of the nasopalatine duct, and its lining may be pseudostratied columnar ciliated epithelium, stratied squamous epithelium, columnar or cuboidal epithelium and combinations of these. As surgical treatment comprises emptying the nasopalatine canal, the specimen always includes the

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artery and nerve that run in this anatomical structure. These are seen within the brous cyst wall and form the most convincing diagnostic feature for this cyst, as the specic appearance of the epithelial lining may be obscured by inammatory changes. Nasolabial cysts are located in the soft tissue just lateral to the nose at the lateral aspect of the maxillary alveolar process and are thought to arise from the nasolacrimal duct. Non-ciliated pseudostratied columnar epithelium with interspersed mucous cells forms the epithelial lining. These features may be lost through squamous metaplasia.18 Apocrine metaplasia of the cyst lining has also been reported.19

Table 2. Odontogenic tumours20 Epithelial Ameloblastoma Calcifying epithelial odontogenic tumour Adenomatoid odontogenic tumour Squamous odontogenic tumour Mesenchymal Odontogenic myxoma Odontogenic broma Cementoblastoma

Odontogenic tumours
Odontogenic tumours comprise a group of lesions that have in common that they arise from the odontogenic tissues, either the epithelial part of the tooth germ, the ectomesenchymal part, or both. Their behaviour varies from frankly neoplastic, including metastatic potential, to non-neoplastic hamartomatous. Some of them may recapitulate normal tooth development, including the formation of dental hard tissues such as enamel, dentin and cementum.20 Table 2 gives an overview of the various entities. Most of them show a radiolucent appearance in which calcied areas may be observed if mineralized tissues are formed. Unless specically stated, they can be cured by simple enucleation. od o n t og e n i c tu m o ur s e p i t h e l ia l Ameloblastoma is the most common odontogenic tumour. The majority occur in the mandible. Radiologically, they are large radiolucent lesions that may be uni- as well as multilocular. Histologically, ameloblastoma consists of either anastomosing epithelial strands (the plexiform type) or discrete epithelial islands (the follicular type) (Figures 7 and 8). Both types may occur within one and the same lesion.21 The cells at the border with the adjacent brous stroma are columnar, with nuclei usually in the apical halve of the cell body away from the basement membrane, and look like the inner enamel epithelium of the enamel organ. The cells lying more centrally are fusiform to polyhedral and loosely connected to each other through cytoplasmic extensions, thus resembling the stellate reticulum part of the enamel organ. Especially in the follicular type, increase of intercellular oedema may cause cysts that coalesce to form the large cavities responsible for the multicystic gross appearance ameloblastomas may show. In the plexiform type, cyst formation is usually the result of stromal degeneration.

Mixed epithelial and mesenchymal

Ameloblastic broma Ameloblastic bro-odontoma Odontoma complex type Odontoma compound type Calcifying odontogenic cyst (calcifying cystic odontogenic tumour dentinogenic ghost cell tumour)

Malignant

Malignant ameloblastoma Ameloblastic carcinoma Primary intraosseous carcinoma Clear cell odontogenic carcinoma Malignant epithelial odontogenic ghost cell tumour Odontogenic sarcoma

The tumour inltrates the adjacent cancellous bone, but the lower cortical border of the mandible and the periosteal layer usually expand without being perforated.22 Spread into soft tissues is highly unusual; when observed, one is probably dealing with ameloblastic carcinoma, a lesion discussed below. Mitotic gures may occur within the peripheral cells as well as in the more centrally located ones. In the absence of cytonuclear atypia and with a normal conguration, they are without any diagnostic or prognostic signicance. Acanthomatous and granular cell type ameloblastomas are variants of follicular ameloblastoma with squamous metaplasia and granular cells, respectively.

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Figure 7. Ameloblastoma of the plexiform type. The epithelial strands are interconnected. The cells facing the stroma are columnar, and more central areas are composed of loosely arranged epithelium with much intercellular oedema and mimicking the stellate reticulum of the enamel organ present during tooth development.

Figure 9. In case of desmoplastic ameloblastoma, the epithelial component is inconspicuous in comparison with the brous stroma. A columnar appearance of the peripheral epithelium is only focally present.

Figure 8. Ameloblastoma of the follicular type. Epithelial nests with peripheral columnar cells and central stellate reticulum-like areas lie dispersed in a brous stroma.

Figure 10. In unicystic ameloblastoma, the tumorous epithelium is conned to the surface that lines the cystic cavity. In case of dropping off of this epithelium in the underlying stroma, treatment should be the same as for the other subtypes.

If keratinization is abundant leading to large cavities lled with keratin, lesions are called keratoameloblastoma.23 In these tumours, acantholysis may lead to a pseudopapillary lining that characterizes the variant called papilliferous keratoameloblastoma. The basal cell (basaloid) ameloblastoma is composed of nests of basaloid cells with a peripheral rim of cuboidal cells; these nests do not display a stellate reticulum-like central zone. Desmoplastic ameloblastoma shows a dense collagenous stroma, the epithelial component being reduced to narrow, compressed strands of epithelium (Figure 9). When these strands broaden to form larger islands, a peripheral rim of dark-staining cuboidal cells and

a compact centre in which spindle-shaped epithelial cells assume a whorling pattern may be discerned. Within the stromal component, active bone formation can be observed.24 Unicystic ameloblastoma represents a cyst that is lined by ameloblastomatous epithelium (Figure 10),25 which may proliferate to form intraluminal nodules with the architecture of plexiform ameloblastoma. Dropping off of this epithelium indicates that there is invasion of the brous cyst wall by ameloblastoma nests. The cyst lining itself sometimes lacks any features indicative of ameloblastoma, these only being shown by deep-seated epithelial nests.26

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Inammatory alterations may obscure the specic histology of unicystic ameloblastoma. In those cases, similar differential diagnostic considerations as already outlined for keratocysts with secondary alterations apply. Ruling out a clinically presumed diagnosis of ameloblastoma may require examination of multiple sections, as only those areas in which there are no inammatory alterations can be considered to be representative of the lesion. Sometimes, ameloblastomas present themselves as a soft tissue swelling occurring in the tooth-bearing areas of maxilla or mandible without involvement of the underlying bone. This peripheral ameloblastoma should not be confused with intraosseous ameloblastomas that spread from within the jaw into the overlying gingiva.27 Treatment of ameloblastoma consists of adequate tumour removal, including a margin of uninvolved tissue. For peripheral ameloblastoma simple excision will be sufcient treatment.26,27 For unicystic ameloblastoma with the ameloblastomatous epithelium conned to the cyst lining, enucleation is adequate therapy, but in case of intramural spread, treatment should be the same as for the other ameloblastoma types.28 Therefore, ruling out the presence of an additional invasive component in what seems at rst glance to be a unicystic ameloblastoma requires extensive histological sampling, as overlooking this component has serious implications for the patient. Epithelial nests resembling ameloblastoma may be found in calcifying odontogenic cysts and ameloblastic bromas, lesions to be discussed below, but displaying additional histological features enabling proper classication and distinction from ameloblastoma. Also, remnants of the enamel organ present in the dental follicle or lying in the wall of odontogenic cysts may mimic ameloblastoma. Usually, these remnants lack a well-developed stellate reticulum-like centre and are much smaller than the ameloblastoma nests. In the maxilla, ameloblastomas may grow into the maxillary sinus. Biopsy specimens from that site may be misdiagnosed as salivary gland tumour, mostly adenoid cystic carcinoma. The calcifying epithelial odontogenic tumour occurs less frequently than ameloblastoma, but is not extremely rare. As with most odontogenic tumours, the mandible is the preferred site. Radiologically, it presents as an irregular mass with radiolucent and radiodense areas. Histologically, the tumour consists of sheets of polygonal cells with ample eosinophilic cytoplasm, distinct cell borders and very conspicuous intercellular bridges. Nuclei are pleomorphic with prominent nucleoli: cells with giant nuclei and multiple nuclei are also present (Figure 11). However, mitotic

Figure 11. A huge variation in nuclear morphology is typical of the calcifying epithelial odontogenic tumour. This should not be mistaken as indicative of malignancy.

gures are absent. Concentrically lamellated calcications are found within the epithelial tumour islands as well as in the surrounding stroma. The latter also contains eosinophilic material that stains like amyloid.29 The tumour grows into the cancellous spaces of the adjacent jaw bone while causing expansion and thinning of the cortical bone. Its extreme cytonuclear pleomorphism should not lead to a diagnosis of poorly differentiated intraosseous cancer, either primary or metastatic. Recognizing the absence of mitotic gures in spite of pleomorphism and the presence of amyloidlike material may be helpful in avoiding this diagnostic error. Adenomatoid odontogenic tumour accounts for approximately 5% of all odontogenic tumours. The maxilla is twice as often involved as the mandible. Quite often, the tumour surrounds the crown of an embedded tooth, thus simulating a dentigerous cyst both clinically and radiologically. Histologically, this tumour consists of a lattice of thin epithelial strands that connect nodules composed of spindle-shaped cells that form whorls. Larger nodules also contain duct-like spaces lined by columnar cells (Figure 12).30 Extracellular eosinophilic material may be present as intercellular droplets as well as located in the above-mentioned duct-like spaces. Concentrically laminated calcied bodies similar to those seen in calcifying epithelial odontogenic tumour may also occur. Areas of cells with ample eosinophilic cytoplasm similar to those observed in the calcifying epithelial odontogenic tumour are sometimes seen.31,32 However, the other histological features of the adenomatoid odontogenic tumour are distinctive enough to prevent confusion between the two lesions.

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Figure 12. Adenomatoid odontogenic tumour shows epithelial nodules interconnected by epithelial strands. The nodules themselves consist of closely packed epithelial spindle cells and columnar cells surrounding empty spaces.

Figure 13. Squamous odontogenic tumour consists of monotonous epithelial cells with ample cytoplasm. They form elds that contain irregular calcications. Absence of peripheral palisading distinguishes the lesion from ameloblastoma.

Squamous odontogenic tumour is extremely are. The lesion is usually conned to the tooth-bearing part of the jaw bone. As it resorbs bone, radiographs of this lesion show a multilocular radiolucency surrounding the roots of the involved teeth. Histologically, squamous odontogenic tumour is composed of islands of well-differentiated, non-keratinizing squamous epithelium surrounded by mature brous connective tissue. In the epithelial islands, cystic degeneration as well as calcication may occur. Invasion into cancellous bone may be present. There is no cellular atypia (Figure 13), and distinction from intraosseous squamous cell carcinoma should therefore not be a problem. Sometimes, squamous odontogenic tumour may be mimicked by intramural squamous epithelial proliferations that can occur in several types of jaw cysts.33 Then, radiology will be decisive, showing either a unilocular lesion in case of a cyst or a multilocular lesion in case of squamous odontogenic tumour. o d on t o g e n i c t um o u r s mesenchymal Odontogenic myxoma equals ameloblastoma in incidence, also belonging to the most common odontogenic tumours. The mandible is involved twice as often as the maxilla. Histologically, myxoma consists of rather monotonous cells with multipolar or bipolar slender cytoplasmic extensions that lie in a myxoid stroma. Nuclei vary from round to fusiform in appearance. Binucleated cells and mitotic gures are present, but scarce. Occasionally, the lesion contains odontogenic epithelial rests.

They are a fortuitous nding without any diagnostic or prognostic signicance. As the tumour does not show encapsulation, it has to be removed including a rim of adjacent normal jaw bone to avoid recurrence (Figure 14).34 A major differential diagnostic problem lies in the fact that myxoma may be mimicked by dental follicle and dental papilla as both contain myxoid areas.3537 Dental papilla tissue can be distinguished from myxoma by the presence of a peripheral layer of columnar odontoblasts as well as a rim of columnar inner enamel epithelium (Figure 15, see also Figure 1B). For both dental papilla and dental follicle, clinical and radiographic data are decisive in avoiding misinterpretation of myxomatous tissue in jaw specimens: in the rst case, a tooth germ lies in the jaw area from which the submitted tissue has been taken, whereas in the second

Figure 14. Low-power view of odontogenic myxoma to illustrate how the tumour engulfs pre-existent jaw bone.

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Figure 15. Dental papilla distinguishable from myxoma by the presence of a rim of enamel epithelium.

case, the tissue sample covers the crown area of an impacted tooth. When myxoma occurs in the upper jaw, the tumour may expand into the maxillary sinus without causing any clinically visible swelling of the jaw, but instead with unilateral nasal obstruction as presenting sign. Biopsy specimens from this site are sometimes misinterpreted as nasal polyposis, the myxoid tumour tissue being mistaken for the oedematous stroma of the polyp. Odontogenic broma is a controversial entity. Uncertainty exists about the histological spectrum that this lesion may show, as well as about its separation from other brous jaw lesions.38 The lesion consists of broblasts lying in a background of myxoid material intermingled with collagen bres that may vary from delicate to coarse. Odontogenic epithelium, either scarce or abundant, may occur. Only rarely, the epithelial component is so conspicuous that differentiation between odontogenic broma and ameloblastoma may be difcult.39 Cell-rich myxoid areas, varying amounts of amorphous calcied globules or mineralized collagenous matrix may also occur in this lesion.38 When odontogenic bromas show a preponderance of myxoid material, distinction from odontogenic myxoma may become problematic. It is probably best to consider such cases as myxomas and to treat them accordingly. All histological features shown by odontogenic broma may also be displayed by the dental follicle.35,37,40,41 In these cases, the radiographic appearance of the lesion, a small radiolucent rim surrounding the crown of a tooth buried within the jaw, will make the distinction. In view of the above summarized features, diagnosis of odontogenic broma requires that the lesion exhibits

Figure 16. Cementoblastoma shows bone-like material lined by swollen cementoblasts and intervening vascular stroma. The lesion is only discernable from osteoblastoma by its connection with root dentin from the adjacent teeth indicated by the presence of a distinct border between bone-like material and tubular dentin.

clinically manifest swelling, shows a radiolucent appearance on radiographs and is connected with an embedded or erupted tooth. Cementoblastomas are rare lesions with a predilection for the mandible. Radiologically, they appear as heavily mineralized tissue masses connected to the apical root part of a tooth. Histologically, cementoblastoma is composed of a vascular, loose-textured brous tissue that surrounds coarse trabeculae of basophilic mineralized material bordered by plump cells with ample cytoplasm and large but not atypical nuclei. Mitotic gures are rare. At the periphery, the mineralized material may form radiating spikes. Also, osteoclastic giant cells occur. The hard tissue component is connected with the root of the involved tooth, which usually shows signs of resorption. The sharp border between the tubular dentin of the root and the hard tissue component forms the hallmark of cementoblastomas (Figure 16). All features of cementoblastoma may also be shown by osteoblastoma, the connection with the tooth root excepted. Therefore, cases in which this connection cannot be demonstrated should be diagnosed as osteoblastoma and not cementoblastoma.42 There are no other differential diagnostic considerations. o d on t o g e n i c t um o u r s m i x ed ep it he li al and m esenchymal Mixed odontogenic tumours are both epithelial and mesenchymal and may recapitulate tissue differentiation, as seen in the developing teeth in varying degrees.

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Deposition of the dental hard tissues enamel and dentin may also occur.20,43 Lesions with an identical histology can show neoplastic as well as hamartomatous behaviour.44,45 With the exception of the odontomas, all are rarely encountered in daily practice. Clinically, they occur both in mandible and maxilla. Radiologically, the appearances vary from radiolucent to radiodense, depending on the presence of dentin and enamel as part of the lesion. They are often associated with an embedded tooth. Nomenclature of the mixed odontogenic tumours depends on their stage of development. Ameloblastic broma lacks a hard tissue component, only displaying soft tissues similar to those found in the immature tooth germ. The epithelial part consists of branching and anastomosing epithelial strands that form knots of varying size with a peripheral rim of columnar cells similar to the enamel organ. The other component is composed of myxoid cell-rich mesenchyme resembling the dental papilla. There is no formation of dental hard tissue. Ameloblastic broma closely resembles ameloblastoma in its epithelial component. The stromal component, however, is entirely different: in ameloblastoma it is mature brous connective tissue, whereas in the ameloblastic broma it is immature, embryonic, cellrich myxoid tissue. Correct differentiation is important, as ameloblastoma requires jaw resection, whereas ameloblastic broma can be treated by enucleation of the lesion. Areas similar to ameloblastic broma may also be observed in the dental follicle.35,37 In this case, it is the radiographic appearance that makes the distinction; a radiolucent rim surrounding an unerupted tooth in case of a dental follicle and an expansive radiolucent jaw lesion in case of ameloblastic broma. Ameloblastic bro-odontomas are lesions that combine a soft tissue component similar to ameloblastic broma with the presence of dentin and enamel (Figure 17).45 The dental hard tissues are arranged haphazardly without any resemblance to the orderly structure of normal teeth. Complex odontoma consists of a usually well-delineated mass of dental hard tissue in a haphazard arrangement. Together with ameloblastoma and myxoma, it is the most frequently encountered odontogenic tumour. These lesions consist for the most part of dentin. Enamel plays a minor role, usually conned to small rims in cavities in the dentin mass. The stroma consists of mature brous connective tissue. Compound odontoma is a less commonly seen malformation consisting of tiny, usually cone-shaped teeth that may vary in number from only a few to numerous. In contrast with the other odonto-

Figure 17. Ameloblastic bro-odontoma shows a mixture of immature odontogenic tissues, also present in the developing teeth. Epithelial areas similar to the enamel organ, myxoid tissue resembling the dental papilla and deposition of enamel matrix and dentin at the interface between epithelium and mesenchyme occur in a random arrangement.

genic tumours, it has a predilection for the anterior mandible. Calcifying odontogenic cyst is one of the more common odontogenic tumours. In its most simple form, it is a cavity with a brous wall and an epithelial lining. This epithelial lining closely mimics that seen in unicystic ameloblastoma, but, in addition, there are ghost cells that may calcify. These ghost cell masses may herniate through the basal lamina to reach the adjacent stroma, where they can act as foreign material and evoke a giant cell reaction. In the brous stroma adjacent to the basal epithelial cells, homogeneous eosinophilic material resembling dentin may be found in varying amounts (Figure 18). The lesion may also be solid, combining the morphology of an ameloblastoma with intraepithelial and stromal ghost cells and dentin-like material. The most recent WHO classication proposes the diagnostic designations calcifying cystic odontogenic tumour and dentinogenic ghost cell tumour to discern between the cystic and the solid lesion.46,47 Areas similar to the calcifying odontogenic cyst may occur in association with other odontogenic tumours, in most instances ameloblastoma and odontoma (Figure 19).48 The combination of calcifying odontogenic cyst and odontoma does not bear clinical consequences, as both lesions respond to conservative treatment. However, when a calcifying odontogenic cyst also contains a component similar to ameloblastoma, one runs into difculties, for in those cases the more radical treatment of ameloblastoma is needed for cure. In that situation, treatment as for ameloblastoma is advisable.

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Figure 18. Calcifying odontogenic cyst resembles ameloblastoma, but can be distinguished by the presence of ghost cells.

Figure 19. Low-power view shows immature odontogenic epithelium and mesenchyme together with enamel and dentin as well as an epithelial component resembling ameloblastoma together with keratin pearls and ghost cells, thus combining the features of immature odontoma with dentinogenic ghost cell tumour.

metastatic deposits. So, it is clinical behaviour and not histology that justies a diagnosis of malignant ameloblastoma.50 Apart from metastasis, malignant ameloblastoma shows no features different from conventional ameloblastoma. Ameloblastic carcinoma is characterized by cells that, although mimicking the architectural pattern of ameloblastoma, exhibit pronounced cytological atypia and mitotic activity, thus allowing separation from the latter lesion. Metastatic lesions are described in the lungs as well in the lymph nodes.50,51 Primary intraosseous carcinoma is a well to poorly differentiated squamous cell carcinoma arising within the jaw, having no initial connection with the oral mucosa, and presumably developing from residues of the odontogenic epithelium.51 The tumour may arise from the epithelial lining of an odontogenic cyst or from enamel epithelium covering the crown of an embedded tooth.5254 Metastasis is to regional lymph nodes as well as lungs.55 Clear cell odontogenic carcinoma is composed of cells with clear cytoplasm.56 These cells form nests and strands, intermingled with smaller islands of cells with eosinophilic cytoplasm (Figure 20). Squamous differentiation has also been reported.57 Cells at the periphery of the nests may show palisading. Metastases are found in lymph nodes as well as in the lungs and skeleton. Malignant epithelial odontogenic ghost cell tumour, also called odontogenic ghost cell carcinoma, is a tumour combining the microscopic features of a benign calcifying odontogenic cyst with a malignant epithelial component. Only a few cases have been reported, thus precluding any conclusions regarding clinicopathological features. Malignancy has been demonstrated by local aggressive growth and distant metastasis.58 The

od o n t og e n i c tu m o ur s malignant Both odontogenic epithelium as well as odontogenic mesenchyme may show neoplastic degeneration, causing either odontogenic carcinomas or odontogenic sarcomas.49 All entities to be mentioned show the clinical presentation and course as well as the radiographic appearance of an intraosseous malignant tumour. They also have in common that they are extremely rare. Malignant (metastasizing) ameloblastoma is an ameloblastoma that metastasizes in spite of an innocuous histological appearance. The primary tumour shows no specic features different from ameloblastomas that do not metastasize. Therefore, this diagnosis can be made only in retrospect, after the occurrence of

Figure 20. Nests of rather monotonous clear cells are the diagnostic hallmark of clear cell odontogenic carcinoma. In spite of this bland histology, the lesion may metastasize locally as well as to distant sites.

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tumour apparently arises most often from malignant transformation of a pre-existing benign calcifying odontogenic cyst.59 Odontogenic sarcomas Several odontogenic sarcomas exist. Depending on whether they contain only soft tissues or also dentin or both dentin and enamel, they are called ameloblastic brosarcoma, ameloblastic brodentinosarcoma or ameloblastic bro-odontosarcoma. This subclassication has no prognostic signicance.60 The tumours may arise de novo or from a pre-existent ameloblastic broma or ameloblastic bro-odontoma.61 Histologically, they are characterized by a sarcomatous component composed of pleomorphic broblasts lying in a myxoid background, a benign epithelial component and, depending on the subtype, also enamel and dentin.

Figure 21. In contrast to the typical appearance of irregular trabeculae of woven bone commonly shown by brous dysplasia, maxillary brous dysplasia may consist of trabeculae of lamellar bone arranged parallel to each other.

Fibro-osseous lesions
The current classication of maxillofacial bro-osseous lesions includes brous dysplasia, ossifying broma and osseous dysplasia.62,63 Table 3 gives an overview of the various entities in this group. Reliable data on their relative frequencies of occurrence are not available. It is the authors experience that brous dysplasia outnumbers the other bro-osseous lesions. Fibrous dysplasia occurs in three clinical subtypes that may all involve the jaws: monostotic, which affects a single bone, polyostotic, which affects multiple bones, and Albrights syndrome, in which multiple bone lesions are accompanied by skin hyperpigmentation and endocrine disturbances. Histologically, brous dysplasia is composed of cellular brous tissue containing trabeculae of woven bone. Cellularity and bone soft tissue proportions are usually rather uniform throughout an individual
Table 3. Fibro-osseous lesions62,63,68 Fibrous dysplasia Ossifying broma Conventional Juvenile trabecular Juvenile psammomatoid Osseous dysplasia Periapical osseous dysplasia Focal osseous dysplasia Florid osseous dysplasia Familial gigantiform cementoma

lesion. In contrast with lesions at other sites, brous dysplasia in the jaw may also show lamellar bone (Figure 21). To discriminate between between brous dysplasia and other bro-osseous lesions, radiographs are mandatory. In case of brous dysplasia, the images show an expanding lesion with a ground-glass, radiodense appearance that merges with the surrounding bone without clear demarcation. Recently, molecular biology has also appeared to be helpful in distinguishing between the two lesions. Activating missense mutations of the gene encoding the a subunit of the stimulatory G protein are a consistent nding in the various forms of brous dysplasia and are not found in any of the other bro-osseous lesions (Figure 22).64,65 Usually, brous dysplasia is a self-limiting disease. Therefore, treatment is required only in case of problems due to local increase in size of the affected bone. Sometimes, an osteosarcoma may arise in brous dysplasia.66 Ossifying broma, formerly also called cementoossifying broma, is a well-demarcated lesion composed of brous tissue that may vary in cellularity from areas with closely packed cells displaying mitotic gures to almost acellular sclerosing parts within one and the same lesion. The mineralized component may consist of plexiform bone, lamellar bone and acellular mineralized material, all sometimes occurring together in one single lesion (Figure 23). In general, radiographs enable the distinction between ossifying broma and brous dysplasia, the rst lesion being mixed radiodense and radiolucent and demarcated from its surroundings, and the latter

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35

40

45

Figure 22. Radiograph showing radiodense lesion in right upper jaw. The lesion merges with its surroundings and involves several bones by crossing sutures. Both features are not shown by ossifying broma (left). Diagnosis of brous dysplasia can be conrmed by molecular analysis. Sequence data showing GNAS mutation, c.602GA (p.Arg201His), reverse sequence illustrated (right).

Figure 23. Low-power view of ossifying broma to show the demarcation from the adjacent cortical bone (left). In this case, the mineralized material mainly consists of smooth-outlined acellular bony particles resembling cementum. In the past, such lesions were called cementifying broma, but this name has been dropped.

homogeneous ground-glass radiodense and without demarcation. There are, however, also characteristic histological differences. At rst, a clear demarcation between lesion and adjacent bone can be observed in properly taken biopsy specimens. Morever, variation in cellularity and different types of mineralized tissues distinguish ossifying broma from brous dysplasia.

Finally, ossifying broma lacks the specic genetic alteration present in brous dysplasia.64,65 Two histological subtypes of ossifying broma have recently been identied. They are the juvenile trabecular and the juvenile psammomatoid ossifying broma.67 The former is usually a rapidly increasing swelling, mostly in young children and mainly involving the upper jaw. Histologically, this tumour shows bands of cellular osteoid together with slender trabeculae of plexiform bone lined by a dense rim of enlarged osteoblasts (Figure 24). Mitoses are present, especially in cell-rich stromal areas. Because of these histological features and the rapid growth, as already mentioned, this type of ossifying broma may be confused with osteosarcoma. However, atypical cellular features or abnormal mitotic gures are not seen and, radiologically, the lesion is demarcated from its surroundings without spread beyond the jaw in adjacent soft tissues (Figure 25). Juvenile psammomatoid ossifying broma consists of extremely cell-rich broblastic stroma with dispersed small ossicles resembling psammoma bodies, hence its name (Figure 26). This type is usually located in the walls of the sinonasal cavities, but sometimes can be encountered in the mandible. At that location, the lesion is usually not solid, but both radiologically and by surgical exploration appearing as an empty cavity

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Figure 24. Juvenile ossifying broma of the trabecular type. Cell-rich garlands of osteoid are its histological hallmark.

Figure 26. Juvenile ossifying broma of the psammomatoid type. Densely packed ossicles in a cell-rich background are typical of this lesion. In this case the lesional tissue is focally distributed in the wall of a bony cavity (radiography shown in Figure 27).

Figure 27. Radiograph of the case from which the histology is shown in Figure 26. Diagnostic tissue may form only a minor component in a large empty cavity.

Figure 25. Radiograph of maxillary juvenile ossifying broma of the trabecular type to demonstrate its demarcated nature, which is very important in making the distinction from osteosarcoma.

suggesting a diagnosis of simple bone cyst. In those cases, diagnostic tissue may be difcult to obtain due to its limitation to a few small foci lying dispersed in a large cavity (Figure 27). Osseous dysplasia is a hamartomatous lesion located in the jaw in the vicinity of the roots of the teeth (Figure 28). The condition occurs in various clinical forms that bear different names (Table 3).68 Periapical osseous dysplasia occurs in the anterior mandible and involves only a few adjacent teeth. A similar limited lesion occurring in the posterior jaw in relationship with the molar teeth is known as focal osseous dysplasia.69 Florid osseous dysplasia is non-expansile,

involves two or more jaw areas and occurs in middleaged Black females. Familial gigantiform cementoma is expansile, involves also multiple jaw areas and occurs at young age. This type of osseous dysplasia shows an autosomal dominant inheritance with variable expression, but sporadic cases without a history of familial involvement have also been reported.70,71 All subtypes have the same histomorphology: cellular brous tissue, trabeculae of woven as well as lamellar bone and spherules of cementum-like material. The distinction between ossifying broma and osseous dysplasia is based on clinical and radiological data. Periapical, focal and orid osseous dysplasia are usually incidental ndings on jaw radiographs taken for other reasons, as they lack any symptoms, whereas ossifying broma is recognized as a tumorous lesion. The expansile familial gigantiform cementoma can be distinguished from ossifying broma by its bilateral

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Figure 29. Osteoclast-like giant cells lying in a cell-rich broblastic background and clustering in areas of haemorrhage. This appearance may be shown by central giant cell granuloma as well as cherubism. The tissue shown in this picture is from a case of cherubism.

Figure 28. Low-power view to show the presence of sclerotic bony particles between root surface and bone of the tooth socket. This histology is common to all types of osseous dysplasia, further subclassication depending on extent as determined by radiological examination.

occurrence in both upper and lower jaw, ossifying broma being a single localized lesion.72

whereas giant cell granulomas are seen from childhood to senescence. Moreover, cherubism has a genetic aetiology, the responsible alteration having been localized to chromosome 4p16.3.73 The expansion of the affected jaw areas causes the angelic face leading to the lesions designation: cherubism. With the onset of puberty, the lesions loose their activity and may mature to brous tissue and bone. Areas with the appearance of giant cell granuloma may occur in lesions otherwise showing all features of either ossifying broma or brous dysplasia. In those cases, the dominant pattern determines the diagnosis. Finally, it should be noted that lesions indistinguishable from giant cell granuloma may occur in cases of hyperparathyroidy.

Giant cell lesions

Central giant cell granuloma and cherubism are both rather common lesions characterized by osteoclastlike giant cells lying in a broblastic background tissue that may vary in cellularity from very dense to cell-poor. Mitotic gures may be encountered, but are usually not numerous and not atypical. The giant cells mostly cluster in areas of haemorrhage, but they also may lie more dispersed within the lesion (Figure 29). Bone formation, if present, is usually conned to the periphery of the lesion. Lesions with an identical histological appearance may occur in the gingiva and at that site are called giant cell epulis. Giant cell granuloma and cherubism are distinguished by the multifocal nature of the latter. In addition, cherubism is a lesion of young children,

Melanotic neuroectodermal tumour of infancy

Clinically, melanotic neuroectodermal tumour of infancy manifests itself as a rapidly growing blue tissue mass, usually at the anterior maxilla in young infants. The lesion consists of dense brous stroma with dispersed cell nests that consist of centrally placed small dark cells without any discernable cytoplasm and peripherally located larger cells with vesicular nuclei and ample cytoplasm with melanin pigment (Figure 30).74 The tumour is thought to arise from cells that have migrated from the neural crest. As mentioned above, the development of the teeth as well as the maxillofacial skeleton depends on the presence of this cell population. Apparently, they can also follow a neuroectodermal pathway, as indicated by their

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Figure 30. Melanotic neuroectodermal tumour of infancy is characterized by small dark cells together with larger cells with pale nuclei and ample cytoplasm that may contain pigment granules. The intervening stroma is usually rather cellular.

immunohistochemical prole that indicates a combination of neural, melanocytic and epithelial differentiation. In spite of its poorly delineated outline, treatment may be conservative and prognosis is generally good, although recurrences are occasionally seen. Approximately 350 cases of this tumour have been reported since its rst description in the beginning of the previous century.75

References
1. Sharpe PT. Neural crest and tooth morphogenesis. Adv. Dent. Res. 2001; 15; 47. 2. Kramer IRH, Pindborg JJ, Shear M. Histological typing of odontogenic tumours, 2nd edn. Berlin: Springer, 1992; 1042. 3. Shear M. Cysts of the oral regions, 3rd edn. Oxford: Wright, 1992; 6. 4. Morgan PR, Johnson NW. Histological, histochemical and ultrastructural studies on the nature of hyaline bodies in odontogenic cysts. J. Oral Pathol. 1974; 3; 127147. 5. Magnusson B, Borrman H. The paradental cyst: a clinicopathologic study of 26 cases. Swed. Dent. J. 1995; 19; 17. 6. Suljak JP, Bohay RN, Wysocki GP. Lateral periodontal cyst: a case report and review of the literature. J. Can. Dent. Assoc. 1998; 64; 5851. 7. Shear M, Pindborg JJ. Microscopic features of the lateral periodontal cyst. Scand. J. Dent. Res. 1975; 83; 103110. 8. Gurol M, Burkes EJ, Jacoway J. Botryoid odontogenic cyst: analysis of 33 cases. J. Periodontol. 1995; 66; 10691073. 9. Gardner DG, Morency R. The glandular odontogenic cyst; a rare lesion that tends to recur. J. Can. Dent. Assoc. 1993; 59; 929 930. 10. Woolgar JA, Rippin JW, Browne RM. A comparative histological study of odontogenic keratocysts in basal cell naevus syndrome and non-syndrome patients. J. Oral Pathol. 1987; 16; 7580. 11. Shear M. The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 1. Clinical and early experimental evidence of aggressive behaviour Oral Oncol. 2002; 38; 219226.

12. Williams TP, Connor FA Jr. Surgical management of the odontogenic keratocyst: aggressive approach. J. Oral Maxillofac. Surg. 1994; 52; 964966. 13. Philipsen HP. Keratocystic odontogenic tumour. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 306307. 14. Wright JM. The odontogenic keratocyst: orthokeratinized variant. Oral Surg. Oral Med. Oral Pathol. 1981; 51; 609618. 15. Nxumalo TN, Shear M. Gingival cysts in adults. J. Oral Pathol. Med. 1992; 21; 309313. 16. Cataldo E, Berkman MD. Cysts of the oral mucosa in newborns. Am. J. Dis. Child. 1968; 16; 4448. 17. Monteleone L, McLellan MS. Epsteins pearls (Bohns nodules) of the palate. J. Oral Surg. 1964; 22; 301304. 18. Wesley RK, Scannel T, Nathan LE. Nasolabial cyst: presentation of a case with a review of the literature. J. Oral Maxillofac. Surg. 1984; 42; 188192. 19. Lopez-Rios F, Lassaletta-Atienza L, Domingo-Carrasco C, Martinez-Tello FJ. Nasolabial cyst: report of a case with extensive apocrine change. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1997; 84; 404406. 20. Philipsen HP, Reichart PA, Slootweg PJ, Slater LJ Neoplasms and tumour-like lesions arising from the odontogenic apparatus and maxillofacial skeleton: introduction. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 285286. 21. Gardner DG, Heikinheimo K, Shear M, Philipsen HP, Coleman H. Ameloblastomas. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 296300. 22. Muller H, Slootweg PJ. The growth characteristics of multilocular ameloblastomas. A histological investigation with some inferences with regard to operative procedures. J. Maxillofac. Surg. 1985; 13; 224230. 23. Saied-Al-Naief NAH, Lumerman H, Ramer M et al. Keratoameloblastoma of the maxilla. A case report and review of the literature. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1997; 84; 535539. 24. Philipsen HP, Reichart PA, Takata T. Desmoplastic ameloblastoma (including hybrid lesion of ameloblastoma). Biological prole based on 100 cases from the literature and own les. Oral Oncol. 2001; 37; 455460. 25. Philipsen HP, Reichart PA. Unicystic ameloblastoma. A review of 193 cases from the literature. Oral Oncol. 1998; 34; 317 325. 26. Gardner DG. Some current concepts on the pathology of ameloblastomas. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1996; 82; 660669. 27. Philipsen HP, Reichart PA, Nikai H, Takata T, Kudo Y. Peripheral ameloblastoma: biological prole based on 160 cases from the literature. Oral Oncol. 2001; 37; 1727. 28. Rosenstein T, Pogrel MA, Smith RA, Regezi JA. Cystic ameloblastoma behavior and treatment of 21 cases. J. Oral Maxillofac. Surg. 2001; 59; 13111316. 29. Takata T, Slootweg PJ. Calcifying epithelial odontogenic tumour. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 302303.

2008 The Author. Journal compilation 2008 Blackwell Publishing Ltd, Histopathology, 54, 401418.

Jaw lesions

417

30. Philipsen HP, Reichart PA, Zhang KH, Nikai AH, Yu QX. Adenomatoid odontogenic tumor: biologic prole based on 499 cases. J. Oral Pathol. Med. 1991; 20; 149158. 31. Okada Y, Mochizuki K, Sigimural M, Noda Y, Mori M. Odontogenic tumor with combined characteristics of adenomatoid odontogenic and calcifying epithelial odontogenic tumors. Pathol. Res. Pract. 1987; 182; 647657. 32. Ledesma CM, Taylor AM, Romero de Leon E, de la Garza Piedra M, Jaukin PG, Robertson JP. Adenomatoid odontogenic tumour with features of calcifying epithelial odontogenic tumour. (The so-called combined epithelial odontogenic tumour.) Clinicopathological report of 12 cases. Eur. J. Cancer Oral Oncol. 1993; 29B; 221224. 33. Wright JM. Squamous odontogenic tumorlike proliferations in odontogenic cysts. Oral Surg. Oral Med. Oral Pathol. 1979; 47; 354358. 34. Slootweg PJ, Wittkampf ARM. Myxoma of the jaws. An analysis of 15 cases. J. Maxillofac. Surg. 1986; 14; 4652. 35. Kim J, Ellis GL. Dental follicular tissue: misinterpretation as odontogenic tumors. J. Oral Maxillofac. Surg. 1993; 51; 762 767. 36. Muller H, Slootweg PJ. A peculiar nding in Le Fort I osteotomy. J. Craniomaxillofac. Surg. 1988; 16; 238239. 37. Suarez PA, Batsakis JG, El-Naggar AJ. Pathology consultation. Dont confuse dental soft tissues with odontogenic tumors. Ann. Otol. Rhinol. Laryngol. 1996; 105; 490494. 38. Philipsen HP, Reichart PA, Sciubba JJ, van der Waal I. Odontogenic broma. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 315. 39. Ide F, Sakshita H, Kusama K. Ameloblastomatoid, central odontogenic broma: an epithelium-rich variant. J. Oral Pathol. Med. 2002; 31; 612614. 40. Dunlap CL. Odontogenic broma. Semin. Diagn. Pathol. 1999; 16; 293296. 41. Lukinmaa PL, Hietanen J, Anttinen J, Ahonen P. Contiguous enlarged dental follicles with histologic features resembling the WHO type of odontogenic broma. Oral Surg. Oral Med. Oral Pathol. 1990; 70; 313317. 42. Slootweg PJ. Cementoblastoma and osteoblastoma: a comparison of histologic features. J. Oral Pathol. Med. 1992; 21; 385 389. 43. Tomich CE. Benign mixed odontogenic tumors. Semin. Diagn. Pathol. 1999; 16; 308316. 44. Slootweg PJ. An analysis of the interrelationship of the mixed odontogenic tumors ameloblastic broma, ameloblastic broodontoma, and the odontomas. Oral Surg. Oral Med. Oral Pathol. 1981; 51; 266276. 45. Philipsen HP, Reichart PA, Praetorius F. Mixed odontogenic tumours and odontomas. Considerations on interrelationship. Review of the literature and presentation of 134 cases of odontomas. Oral Oncol. 1997; 33; 8699. 46. Praetorius F, Ledesma-Montes C. Calcifying cystic odontogenic tumour. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 313. 47. Praetorius F, Ledesma-Montes C. Dentinogenic ghost cell tumour. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 314.

48. Praetorius F, Hjorting-Hansen E, Gorlin RJ, Vickers RA. Calcifying odontogenic cyst. Range, variations and neoplastic potential. Acta Odontol. Scand. 1981; 39; 227240. 49. Slootweg PJ. Malignant odontogenic tumors; an overview. Mund. Kiefer. Gesichtschir. 2002; 6; 295302. 50. Sciubba JJ, Eversole LR, Slootweg PJ. Odontogenic ameloblastic carcinomas. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 287289. 51. Eversole LR. Malignant epithelial odontogenic tumors. Semin. Diagn. Pathol. 1999; 16; 317324. 52. Johnson LM, Sapp JP, McIntire DN. Squamous cell carcinoma arising in a dentigerous cyst. J. Oral Maxillofac. Surg. 1994; 52; 987990. 53. Makowski GJ, McGuff S, van Sickels JE. Squamous cell carcinoma in a maxillary odontogenic keratocyst. J. Oral Maxillofac. Surg. 2001; 59; 7680. 54. Slootweg PJ. Carcinoma arising from reduced enamel epithelium. J. Oral Pathol. 1987; 16; 479482. 55. Zwetyenga N, Pinsolle J, Rivel J, Majoufre-Lefebvre C, Faucher A, Pinsolle V. Primary intraosseous carcinoma of the jaws. Arch. Otolaryngol. Head Neck Surg. 2001; 127; 794797. 56. Hansen LS, Eversole LR, Green TL, Powell NB. Clear cell odontogenic tumor a new histologic variant with aggressive potential. Head. Neck. Surg. 1985; 8; 115123. 57. Brinck U, Gunawan B, Schulten HJ, Pinzon W, Fischer U, Fuezesi L. Clear cell odontogenic carcinoma with pulmonary metastases resembling pulmonary meningothelial-like nodules. Virchows Arch. 2001; 438; 412417. 58. Lu Y, Mock D, Takata T, Jordan RC. Odontogenic ghost cell carcinoma: report of four new cases and review of the literature. J. Oral Pathol. Med. 1999; 28; 323329. 59. Li TJ, Yu SF. Clinicopathologic spectrum of the so-called calcifying odontogenic cysts. A study of 21 intraosseous cases with reconsideration of the terminology and classication. Am. J. Surg. Pathol. 2003; 27; 372384. 60. Altini M, Thompson SH, Lownie JF, Berezowski BB. Ameloblastic sarcoma of the mandible. J. Oral Maxillofac. Surg. 1985; 43; 789 794. 61. Muller S, Parker DC, Kapadia SB, Budnick SD, Barnes L. Ameloblastic brosarcoma of the jaws. A clinicopathologic and DNA analysis of ve cases and review of the literature with discussion of its relationship to ameloblastic broma. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1995; 79; 469477. 62. Brannon RB, Fowler CB. Benign bro-osseous lesions: a review of current concepts. Adv. Anat. Pathol. 2001; 8; 126143. 63. Slootweg PJ. Maxillofacial bro-osseous lesions: classication and differential diagnosis. Semin. Diagn. Pathol. 1996; 13; 104112. 64. Pollandt K, Engels C, Kaiser E, Werner M, Delling G. Gsa gene mutations in monostotic brous dysplasia of bone and brous dysplasia-like low-grade central osteosarcoma. Virchows Arch. 2001; 439; 170175. 65. Toyosawa S, Yuki M, Kishino M et al. Ossifying broma vs brous dysplasia of the jaw: molecular and immunological characterization. Mod. Pathol. 2007; 20; 389396. 66. Ebata K, Takeshi U, Tohnai I, Kaneda T. Chondrosarcoma and osteosarcoma arising in polyostotic brous dysplasia. J. Oral Maxillofac. Surg. 1992; 50; 761764. 67. El-Mofty SK. Psammomatoid and trabecular juvenile ossifying broma of the craniofacial skeleton: two distinct clinicopathologic entities. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2002; 93; 296304.

2008 The Author. Journal compilation 2008 Blackwell Publishing Ltd, Histopathology, 54, 401418.

418

P J Slootweg

68. Slootweg PJ. Osseous dysplasias. In Barnes L, Eveson JW, Reichart PA, Sidransky D eds. World Health Organization classication of tumours. Pathology and genetics of tumours of the head and neck. Lyon: IARC, 2005; 323. 69. Summerlin DJ, Tomich CE. Focal cemento-osseous dysplasia: a clinicopathologic study of 221 cases. Oral Surg. Oral Med. Oral Pathol. 1994; 78; 611620. 70. Young SK, Markowitz NR, Sullivan S, Seale TW, Hirschi R. Familial gigantiform cementoma: classication and presentation of a large pedigree. Oral Surg. Oral Med. Oral Pathol. 1989; 68; 740747. 71. Abdelsayed RA, Eversole LR, Singh BS, Scarbrough FE. Gigantiform cementoma: clinicopathologic presentation of 3 cases. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2001; 91; 438444.

72. Su L, Weathers DR, Waldron CA. Distinguishing features of focal cemento-osseous dysplasias and cemento-ossifying bromas. II. A clinical and radiologic spectrum of 316 cases. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 1997; 84; 540549. 73. Mangion J, Rahman N, Edkins S et al. The gene for cherubism maps to chromosome 4p16.3. Am. J. Hum. Genet. 1999; 65; 151157. 74. Barrett AW, Morgan M, Ramsay AD, Farthing PM, Newman L, Speight PM. A clinicopathologic and immunohistochemical analysis of melanotic neuroectodermal tumor of infancy. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2002; 93; 688698. 75. Kruse-Losler B, Gaertner C, Burger H, Seper L, Joos U, Kleinheinz J. Melanotic neuroectodermal tumor of infancy: systematic review of the literature and presentation of a case. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 2006; 102; 204216.

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