Odontogenic Tumors and Other Lesions
Humans have suffered from odontogenic tumors and cysts for thousands of years (Fig. 12.1). Tumors arising in relation to the teeth were described in the 18th century1 and the first attempt at classification was by Broca in 1868.2 Thoma and Goldman 1946 classified them according to their tissue of origin: epithelial, mesenchymal, and mixed odontogenic.3 These tumors are renowned for their variation in growth, behavior, and histology and debate continues to this day with regard to their classification.
The name “odontogenic tumor” covers a group of neoplasms and hamartomatous lesions originating from cells involved in the formation of teeth or remnants of tissues that had been implicated in odontogenesis. Very few of these lesions actually have formed dental hard tissue in them; most are rare and many exceedingly rare. Recent use of electron microscopy, immunohistochemistry, and molecular biological techniques has considerably increased our knowledge of these tumors and their classification becomes ever more complex.
The tumors occur in three locations: (1) intraosseous (centrally) within the jaws, (2) extraosseous (peripherally) in the alveolar mucosa or gingiva adjacent to tooth-bearing areas, and (3) in the cranial base as one of the variants of the craniopharyngioma.
Philipsen and Reichart4 have published an excellent review of the history of classification of odontogenic tumors and reading of this is highly recommended if you wish to evaluate the matter further. For the purposes of the remainder of this chapter, the WHO 2005 classification will be used, see Table 12.1.5
Etiology
The etiology of odontogenic tumors remains unknown apart from some recent indications suggesting genetic factors playing a role in some cases. The overall pathogenesis is only partially understood and the reader is referred again to the excellent 2004 review by Philipsen and Reichart.4
Despite the WHO histological classification of odontogenic tumors commencing with a list of malignant tumors, it seems more appropriate to initiate the discussion of these lesions with a review of benign tumors. As a consequence of a close working relationship with dental and maxillofacial colleagues from every aspect of the discipline at the Eastman Dental Hospital and Institute of Oral Pathology, London, UK, we are fortunately able to base some of this chapter on personal experience, although our knowledge of the exceedingly rare tumors is based on literature reports of cases that often amount to only a single description.
While the majority of small odontogenic lesions will present to dental and oral surgeons, those lesions expanding into the maxillary sinuses, orbit, and skull base may well present to maxillofacial, ENT, and occasionally ophthalmological colleagues. In this chapter, we have endeavored to cover both the commoner and rarer lesions that can involve the sinonasal and skull base areas in contrast to the mandibular sites.
Benign Odontogenic Tumors
This group of tumors comprises those of essentially odontogenic epithelium without evidence of odontogenic ectomesenchyme and with a mature fibrous stroma.
Ameloblastoma
(ICD-O code 9310/0)
Ameloblastomas are currently classified into four different types by WHO, although a variety of additional names have been used in the literature in the past.
Ameloblastoma, solid/multicystic
Ameloblastoma, extraosseous/peripheral type
Ameloblastoma—desmoplastic type (DESAM)
Ameloblastoma—unicystic type
Ameloblastoma, Solid/Multicystic
This central, solid/multicystic ameloblastoma is a histologically benign tumor originating from epithelial components of the embryonic tooth. It is a locally invasive neoplasm of the jaws with potentially a high rate of recurrence, but a low tendency to metastasize.
Etiology
The etiology essentially remains unknown, although studies of cytokeratins6 support the hypothesis that ameloblastomas are of odontogenic origin and not, as has been suggested by other authors, derivatives of basal cells of the oral epithelium.
Synonyms
Many names have been used in the older literature, including the following examples: conventional ameloblastoma, classical intraosseous ameloblastoma, multicystic jaw tumor, epithelial odontoma, epithelioma ameloblastoides, cystoma, adamantinoma.
Incidence
While numerous publications in the past have produced figures for the incidence of these lesions, few contain any subdivisions in ameloblastoma variants and there has been much confusion with other odontogenic tumors. However, overall, ameloblastoma is probably the second most common odontogenic tumor after the odontomas. The well-known report by Shear et al evaluating the incidence rates in South Africa between 1965 and 1974 shows that ameloblastoma is much more common in black than white Africans.7 Larsson et al in 1978 reported on all cases of ameloblastoma from the Swedish Cancer Registry in the period 1958–1971.8 They estimated a true incidence of 0.6 cases per year per million people. This provides a reasonable baseline estimate for the incidence of ameloblastoma in the worldwide white population.
The largest review of ameloblastomas was published by Reichart et al in 1995, profiling 3,677 cases published in many languages between 1960 and 1993.9 There were 693 case reports and the rest from reviews. As Gardner pointed out in 1999, numbers from reports do not necessarily reflect the occurrence of ameloblastomas in any particular racial group but rather the number of published cases in those groups.10 It does not necessarily indicate the actual prevalence in a population. Cases reported from Africa are an outstanding example in that, anecdotally, they are thought to be even more common than the literature implies.
Site
The Reichart et al review9 showed the ratio between maxillary and mandibular tumors (of all variants of ameloblastoma) to be 1:5.8. The maxillary sinus was more often affected in males than females. While there are numerous studies showing the presence of ameloblastomas within the sinonasal cavity, particularly the maxilla, there are rarer reports that document true, primary sinonasal ameloblastomas without connection to gnathic sites11–17 and there is a particularly useful review by Schafer et al of 24 cases published in 1998.18
Those ameloblastomas arising from the gnathic maxilla and extending into the sinuses have a mean age of occurrence between 35 and 45 years,19 whereas those tumors reported as originating from the sinonasal tract have a distinct predilection for older men, aged between the sixth and eighth decades of life. The gnathic tumors frequently present as a painless expansion of the upper jaw, most commonly posterior to the canine tooth with approximately half being sited in the molar region. Approximately 15% of them progress to involve the antrum and nasal floor. Ameloblastomas arising in the posterior aspect of the maxilla can reach a large size before diagnosis as a consequence of expanding in the antrum, cheek, or palate. Those tumors reported as arising from the sinonasal tract, present with unilateral nasal obstruction with or without symptoms of sinusitis. Seven out the 24 cases of primary ameloblastoma of the sinonasal tract reported by Schafer additionally presented with epistaxis.18 In contrast to the overall published literature on ameloblastoma, 19 of 21 of these cases where the patient′s race was documented were white and only 2 were African American. The duration of symptoms ranged from one month to several years. On examination, 9 of these 24 sinonasal ameloblastomas involved the nasal cavity alone. Six were confined to the paranasal sinuses (maxillary, frontal, ethmoid or sphenoid) and 9 involved both the nasal cavity and paranasal sinuses at presentation.
Diagnostic Features
Clinical Features
The mean ages from case reports can also be misleading as there are significant differences between the variants of ameloblastoma with solid/multicystic and central ameloblastoma having a mean age at presentation of around 40 years, whereas unicystic ameloblastoma (UNAM) has a mean age at presentation of between 14 and 26 years in the literature. Again, there appear to be racial differences with the majority of ameloblastomas in white children being of the unicystic variety whereas the pattern in African children seems to resemble more that of adults.20,21
Notable in the review by Reichart et al9 was that they found the mean age of patients with tumors involving the maxilla to be 47.0 years in contrast to those with tumors arising in the mandible, who had a mean age of 35.2 years. This again, however, may be explained by the fact that UNAMs are rare in the maxilla. Approximately 30% of solid/multicystic ameloblastomas and extraosseous, peripheral type ameloblastomas occur in the maxilla. There is approximately equal male-to-female distribution.
As might be expected, these patients present with a painless swelling of the cheek, gingiva, or palate, occasionally nasal obstruction, and sometimes distortion of the dentition with malocclusion, ill-fitting dentures, or loosening of teeth. In our small cohort of 6 patients, comprising 5 males and 1 female, aged 16 to 80 years (mean 50.8 years) all had some degree of facial swelling, 2 had nasal obstruction, and 2 had oroantral fistula (Table 12.2).
Imaging
In contrast to the characteristic multilocular and radiolucent presentation of ameloblastomas within the jaws (“soap bubble appearance”), sinonasal lesions have been most often described radiographically as solid masses filling the nasal cavity and sinuses with bone destruction and remodeling in some cases. Primary origin in or continuity with the maxillary alveolar area is not demonstrated in any of the true sinonasal cases. On examination, the lesions ranged from a size of several millimeters to 9 cm in the sinonasal lesions reported by Schafer et al.18 In contrast, Reichart et al noted a mean size of 4.6 cm for maxillary tumors with many in excess of 10 cm. 9 In this latter group, embedded teeth were detected in 8.7% and root resorption of neighboring teeth in 3.8%.
Histological Features
Microscopically, these tumors are usually solid in appearance with a glistening gray-white or yellow-tan coloration. The consistency varies from solid to cystic, although the sinonasal lesions rarely appear cystic on gross examination.
Microscopically, these tumors consist of odontogenic epithelium contained in a relatively cell-poor collagenous stroma. Two predominant growth patterns—follicular and plexiform—are recognized with four main cell types: stellate reticulum-like cell type, acanthomatous (squamous cell) cell type, granular cell type, and basal cell type. Interestingly, the plexiform pattern comprising of a network of long anastomosing cords of odontogenic epithelium was the sole or predominant histological pattern in 22 out of the 24 sinonasal cases (92%) studied by Schafer et al.18 Both patterns may be present in the same tumor and there is no general consensus whether growth pattern is related to the clinical behavior of the tumor. Both the stellate reticulum-like component and the acanthomatous pattern, characterized by squamous metaplasia and keratin formation of the central portions of the epithelial islands, made up only a small secondary or focal component of the sinonasal plexiform pattern ameloblastomas. In 15 of Schafer′s 24 sinonasal cases, the ameloblastomatous proliferation could be observed arising in direct continuity with the intact sinonasal surface mucosal epithelium.18 They conclude from this that this form of peripheral ameloblastoma most likely originates from pluripotential cells in the mucosal surface epithelium. Alternatively, the ameloblastomatous epithelium could have originated in the submucosa and secondarily extended to involve the surface epithelium, but certainly no odontogenic dental lamina within the submucosa was observed in any of the cases.
Immunohistochemical Features
There has been considerable interest in ameloblastoma, as it is one of the commonest odontogenic tumors, and there are numerous publications on immunohistochemistry and with molecular biological investigations. In addition to electron microscopy, studies have looked at oncogenes, gene modifications, tumor suppressor genes, DNA repair genes, oncovirus growth factors, telomerase, cell cycle regulators, apoptosis-related factors, regulators of tooth development, cell adhesion molecules, matrixdegrading proteinases, angiogenic factors, and osteolytic cytokines. The reader is referred to two comprehensive reviews by Kumamoto in 200622 and Praetorius in 200923 (see ref. 23: p. 1208).
Differential Diagnosis
Ameloblastomas with a plexiform growth pattern have to be distinguished from hyperplastic odontogenic epithelium, which is commonly seen in the walls of odontogenic cysts. The granular cell type of solid/multicystic ameloblastoma may be confused with the granular cell odontogenic tumor (GCOT), but while the ameloblastoma is an epithelial tumor, the granular cell tumor is ectomesenchymal; and while cords and islands of odontogenic epithelium are seen, they are different from the proliferating epithelium of ameloblastoma.
Treatment and Prognosis
There continues to be a difference of opinion in the world literature about the preferable methods of treatment of the solid/multicystic variant of ameloblastoma either in the maxilla or in the mandible. What is not in doubt is that recurrence rates of approximately one-third of the cases are not unusual even in recent times.24 Some centers have strongly advocated radical surgical procedures and Carson in 2006 reported that conservative treatment was unpredictable and that recurrent or persistent disease could not then always be treated adequately. They studied 82 cases of resected solid/multicystic ameloblastomas showing that tumor extends up to 8 mm beyond its radiographic demarcation (mean 4.5 mm) and they recommended resection with a 1 to 1.5 cm linear bone margin whenever possible. Ghandhi et al 200625 showed that primary care by conservative treatment (comparing cases from West Scotland with those in San Francisco) led to recurrence in ~80% of cases. Recurrence rates following local enucleation and curettage seem unacceptably high.
Much of the older literature with regard to maxillary and sinonasal tract lesions demonstrates inadequate surgery by means of intranasal polypectomy type procedures, limited Caldwell-Luc approaches, minimal excision and curettage, and inadequate partial maxillectomy. Reluctance to consider a facial incision, particularly in children, such as lateral rhinotomy or a Weber–Fergusson incision, can now be completely discarded. Modern, high-quality and thorough endoscopic techniques, external rhinoplasty type approaches, and midfacial degloving procedures allow radical removal of these lesions with magnification and additional frozen section control with further endoscopic removal in the sinonasal cases should there be any concerns following definitive histopathology. It is therefore to be hoped that in future the high level of recurrence within the literature, and both early and late recurrence of disease (in the latter often several years after surgical treatment), will not continue to be widely reported.
Schafer et al18 found that 5 of the 24 patients (21%) experienced at least one recurrence, generally within a period of 1 to 2 years after the initial treatment, but one patient did not experience recurrence until 13 years after initial surgery. Recurrences of gnathic ameloblastomas have been reported up to 30 years after primary surgery.26 Schafer′s 24 cases of sinonasal ameloblastoma had follow-up periods ranging from 1 year to 44 years (average 9.5 years) and all were alive without evidence of disease, or had died of unrelated causes without evidence of recurrence.18 One case was lost to follow-up.
In our group, two had already undergone inadequate surgery and all required some form of maxillectomy. In the two more recent cases this was successfully achieved via a midfacial degloving approach. All but one have survived long-term follow-up but unfortunately one has been lost to follow-up and an elderly man with the most advanced lesion treated in 1963 died of his disease after 3 years, having initially refused treatment.
Key Points
Approximately 15% of these lesions progress to involve the maxillary antrum and nasal floor.
Duration of symptoms may extend over years.
Sinonasal lesions may be several centimeters in diameter.
A high rate of local recurrence has been common in the past.
Ameloblastoma, Extraosseous/Peripheral Type
Peripheral ameloblastoma (PERAM) is a rare benign, slowly growing, exophytic lesion occurring on the gingiva or the attached alveolar ridge mucosa in edentulous areas. Philipsen et al,27 reviewing the literature of 160 cases, found 46 (29.1%) located in the maxilla. The most common area was the soft palatal tissue of the tuberosity area. Lesions are generally painless with a long history beyond a year. None were associated with any significant invasion of bone or the sinonasal area. Treatment was by local excision.
Ameloblastoma, Desmoplastic Type
Definition
Ameloblastoma, desmoplastic type (DESAM) is a rare, benign, locally infiltrative tumor that is considered a variant of ameloblastoma.
Diagnostic Features
Clinical Features
Philipsen et al27 reviewed 100 cases from the literature and their own files showing that this rare tumor occurs in females in the fourth and fifth decades but with a male peak in the sixth decade. It is rare outside of the 30 to 60 age group and, in contrast to the much more common solid/multicystic ameloblastoma, it had an almost equal distribution of cases within the maxilla and mandible. Notably, 7 cases involved the entire maxilla and 3 of these maxillary cases involved the nasal cavity and crossed the midline. Again, in contrast to the solid/multicystic ameloblastoma, the majority of cases were in the anterior aspect of the upper jaw. The most common clinical presentation was a painless hard swelling often present for years prior to presentation.
Imaging
Of the cases reviewed by Philipsen et al,27 53% showed a mixed radiolucent/radiopaque pattern with ill-defined margins making the lesion look more suggestive of fibroosseous disease than of ameloblastoma. Thompson et al,28 in an excellent paper, demonstrated the value of CT and MRI, in particular the details of the margins of the lesion and the detection of the mixed fine and coarse trabecular pattern at the periphery of the lesion.
Histological Features
This was described in detail by Eversole et al in their early defining paper of 1984.29
DESAM is composed of strands and islands of tumor epithelium with a high cellular density. The epithelium lacks stellate reticulum cells and columnar basal cells and the epithelial cells are small, spindle-shaped, or polygonal. There is abundant stroma with pronounced collagen formation and moderate cellularity. Myxomatous changes may be seen around the epithelial islands in addition to a cellular amorphous eosinic material. Invasion of tumor tissue into surrounding bone has been noted in some cases, but a mixture of bone and trabecular resorption and new bone production may be found at the periphery of the tumor. Debate continues about whether DESAM should be considered as a separate lesion from conventional ameloblastomas. Lesions with the histopathological features of both occurring simultaneously have been described.30
Immunohistochemical Features
Multiple studies have been undertaken to differentiate desmoplastic ameloblastoma from solid/multicystic ameloblastoma, perhaps the most notable being the Takata et al study31 comparing 7 cases of DESAM with 10 cases of conventional ameloblastoma showing a marked immunoexpression in both peripheral and central cells in the tumor nests of DESAMs but none in conventional ameloblastoma. The TGF-β produced by the tumor cells is believed to play a part in the desmoplastic matrix formation. Philipsen et al32 detected marked staining or collagen type VI in the stroma adjacent to tumor islands in DESAMs. Conventional ameloblastomas were negative.
Treatment and Prognosis
The treatment of desmoplastic ameloblastoma is essentially the same as that advocated for solid/multicystic ameloblastoma: resection with at least 1 cm of bony margin; and in the maxilla it may be necessary to undertake hemi or total maxillectomy to achieve this. Again, there are cases reported recurring years after excision.33
Ameloblastoma, Unicystic Type
Unicystic ameloblastoma (UNAM) is an odontogenic cystic neoplasm with a single, often large lumen and development of an initial intralining, intraluminal, or intramural ameloblastoma or combinations of these. The pathologist requires the entire specimen to make an exact diagnosis of the tumor.
Synonyms
Cystogenic ameloblastoma, plexiform unicystic ameloblastoma, intracystic ameloblastoma, cystic ameloblastoma, unilocular ameloblastoma, extensive dentigerous cyst, and intracystic ameloblastic papilloma.
Diagnosis and Specific Features
Clinical Features
All series report more than 90% of these lesions occurring in the mandible with only small numbers of tumors in the maxilla.34 Most patients present with an incidental swelling that on imaging is a well-defined unilocular radiolucency.
Treatment and Prognosis
These lesions are rarely suspected to be an ameloblastoma preoperatively and are usually removed by enucleation and curettage as a nonneoplastic odontogenic cyst. When the final diagnosis is made following histopathology, the risk of recurrence is related to the histological type and if the diagnosis is UNAM grade III (intramural), an additional marginal segmental resection of the upper jaw or partial maxillectomy may be required to prevent recurrence.
Key Points
These lesions are very rare in the maxilla.
The pathologist requires the entire specimen to make an exact diagnosis of the tumor.
Squamous Odontogenic Tumor
Definition
(ICD-O code 9312/0)
Squamous odontogenic tumor is a locally infiltrative neoplasm consisting of islands of well-differentiated squamous epithelium in a fibrous stroma. It usually occurs intraosseously, properly developing in the periodontal ligaments between the roots of vital erupted permanent teeth. Approximately 50 cases have been published, of which 36 were reviewed by Philipsen and Reichart.35 Patients may present with simple swelling, local pain, or mobility of teeth. Imaging shows unilocular or triangular radiolucency between the roots of adjacent teeth.
Treatment and Prognosis
None have been recorded to involve the nose and sinuses and conservative surgical procedures in terms of enucleation and curettage or minimal local incision are considered to be adequate, although recurrence has been documented.36
Calcifying Epithelial Odontogenic Tumor
Definition
(ICD-O code 9340/0)
Calcifying epithelial odontogenic tumor (CEOT) is a benign, slow-growing, nonencapsulated and locally invasive lesion. It has a distinctive histomorphological pattern characterized by variable sheets and islands of eosinophilic, polyhedral, and often pleomorphic cells, which merge into an eosinophilic, amorphous substance that stains with amyloid marker and tends to calcify, although not in all cases. The tumor was first described by Pindborg in 1955 and its most common synonym is Pindborg tumor.37,38
Incidence and Site
This tumor is rare, with ~200 cases at present published in the literature. Franklin and Pindborg reviewed 113 cases and Philipsen and Reichart reviewed 181 cases.39,40 CEOT occurs as an intraosseous and a less aggressive extraosseous variant with a roughly equal male-to-female ratio and an age range of 8 to 92 years. The extraosseous cases are more likely to occur in the anterior segment of the jaw and the mandible-to-maxillary ratio is 2:1. Multifocal examples are extremely rare but have been described.41
Diagnostic Features
Clinical Features
These tumors grow slowly and are often symptomless, presenting as a firm swelling from either jaw but there are examples of extensive lesions involving the nasal cavity and maxillary sinus to a degree where they present with unilateral nasal obstruction, epistaxis, pain, and proptosis.39 Bridle et al in 2006 published an extensive case involving the whole maxilla causing significant displacement of the eye in a 30-year-old woman.42
Imaging
Imaging is essentially unhelpful as there is considerable variation in these lesions, with findings ranging from a well-circumscribed unilocular radiolucency to a diffuse, poorly demarcated lesion with small intralesional septa producing a multiloculated pattern. Additionally, there may be flecks of calcification and overall these lesions may resemble an ameloblastoma or a dentigerous cyst. With increasing calcification, the radiological differential diagnosis starts to include ossifying fibroma and odontogenic fibroma.43
Histological Features
Microscopically these lesions appear to be a solid tumor; cystic changes are not seen. The tumor consists of islands and sheets of polyhedral epithelial cells with abundant eosinophilic cytoplasm, sharply defined cell borders, and well-developed intercellular bridges, all within a fibrous stroma. Mitotic figures are rarely encountered; indeed, if they are, frequent malignant transformation must be suspected. Nuclei are usually pleomorphic. Giant nuclei are quite common. Concentric rings of calcification may be present either within or around the tumor cells, which lie in a homogeneous hyaline material that is amyloid. The amount of amyloid varies, with some tumors being predominantly epithelial. Calcification is more commonly absent in extraosseous tumors and clear cells containing glycogen may be present within the epithelial nests and make up a significant proportion of the tumor.40
Differential Diagnosis
As a consequence of cytonuclear pleomorphism and intercellular bridges, it is important to avoid mistaking CEOT for an intraosseous squamous carcinoma. A clear cell variant of the CEOT has been described as having a more aggressive behavior.44
Treatment and Prognosis
The size of lesions at the time of surgery varies between a few millimeters and as much as 10 cm within the reported literature and hence treatment has varied from simple enucleation and curettage to hemi and total maxillectomy. Treatment will clearly be dictated by the extent and site of the tumor. All publications are agreed that complete removal is necessary with a tumor-free surgical margin if at all possible, and long-term follow-up is advised.45 The older surgical series, as with other tumors in this group, report notable recurrence rates; for example, Franklin and Pindborg in 197639 reviewing 17 cases with a follow-up of 10 years or more, reported a recurrence rate of 14%. It is likely that this is due to inadequate treatment, and modern surgical approaches and pathology evaluation could reduce this. Occasional cases of malignant transformation have been reported.46
Key Point
The size of lesions varies from a few millimeters to 10 cm with substantial involvement of the nasal cavity, maxillary sinus, and orbital floor.
Adenomatoid Odontogenic Tumor
Definition
(ICD-O code 9300/0)
Adenomatoid odontogenic tumor (AOT) is a slow-growing, encapsulated epithelial odontogenic tumor that has a single histomorphological pattern with whirled nodules of spindle cells, plexiform double cell strands, and microcystic or ductlike spaces. It has a limited growth potential and debate continues whether or not it is a neoplasm.47
Etiology
The pathogenesis of AOT is not known but it is thought to develop from residues of the dental lamina and proliferations of odontogenic epithelium adjacent to the reduced enamel epithelium of unerupted teeth.
Synonyms
Adenoameloblastoma.
Incidence and Site
Although AOT is an uncommon lesion, Philipsen et al48 found a total of 1,082 cases published from 12 different countries and it is generally regarded as the third or fourth most common odontogenic tumor. More than 95% of all cases are interosseous, occurring within the bone, and the maxilla is affected twice as often as the mandible. The commonest site is adjacent to the upper canine area and the peripheral extraosseous type of lesion has been described, almost all of which have occurred in the anterior part of the maxilla.49
Diagnostic Features
Clinical Features
Females are affected approximately twice as commonly as males; few patients have been reported older than 30 years48 and ~50% of patients are teenagers. Intraosseous AOTs are usually diagnosed during dental radiographic imaging to evaluate the cause of any disturbance in tooth eruption. The growth rate is known to be slow and larger lesions which may involve the entire maxillary sinus reaching the orbital floor and impacting on the nasal cavity may be painless or only associated with slight pain.
Imaging
As a consequence of the majority of these lesions developing at an early age and often in the canine area, the eruption of the permanent canines is disturbed and the AOT wraps around the crown of the tooth and sometimes the entire tooth. This so-called “follicular” AOT simulates a dentigerous cyst unless the radiolucency extends apically along the root past the cement–enamel junction. The lesions are usually well defined and unilocular and the intraoral film commonly shows scattered, fine radiopacities within the radiolucent area.50 Follicular type is by far the commonest form of AOT, but intraosseous AOTs that are unrelated to an erupted tooth (“extrafollicular type”) present as well-delineated radiolucent lesions. This extrafollicular type can simulate a residual, a periapical radicular, a lateral radicular, or a lateral periodontal cyst, but sizable lesions within the upper jaw have been described that invade the maxillary sinus.51–53
Leon et al53 found a range in the size of these lesions between 1 cm and 7 cm, with an average of 2.9 cm.
Histological Features
Microscopically, the tumors are usually well circumscribed and vary from solid to cystic, and may be situated around the crown of a tooth. Interestingly, the histopathology shows a consistent pattern irrespective of the location of the lesion in the jaws. The solid lesions show variably sized, solid nodules of columnar or cuboidal cells of odontogenic epithelium that may form small nests (“rosettes”). Between the epithelial cells and in the center of the rosette is eosinophilic amorphous material (“tumor droplets”).
Cystic spaces of variable size may be seen between the nodules (“ductlike spaces”). These are not present in all tumors. These ductlike spaces are lined by single rows of columnar epithelial cells and actually represent pseudolumina formed by the secretion of the columnar epithelial cells. The cytoplasm of these cells is usually lightly stained and the oval nuclei are polarized away from the lumen. Larger cystic spaces are usually lined with cuboidal epithelium without polarization of the nuclei. Some of the cystic spaces may show invagination. Additionally, there may be scattered foci of polyhedral squamous cells in the tumor.
An additional, well-recognized, cellular pattern is found in some tumors where long, narrow epithelial strands of cubic cells are seen that may be in single or double layers and form large loops in a plexiform pattern. Loose stroma inside these loops may sometimes be missing and this pattern is more common toward the periphery of the lesion. There may be a hyaline, dysplastic material or calcified osteodentin in AOTs. This is thought to be due to a metaplastic process as odontogenic ectomesenchyme is absent. In rare cases, dentinlike material containing dentinal tubules may occur. AOTs may have areas with a similar pattern to calcifying epithelial odontogenic tumor (CEOT) but these are considered as a histological variant of AOT and do not appear to change the behavior of the AOT. AOTs may also contain areas that mimic calcifying ghost cell odontogenic cysts or other odontogenic tumors or hamartomas. None have been shown to alter the situation.
Treatment and Prognosis
In contrast to other odontogenic tumors, published reports agree that enucleation of a tumor followed by curettage is all that is necessary and the thick connective tissue capsule facilitates the enucleation. The risk of recurrence is extremely low and malignant transformation has never been described. This agrees with the fact that many authors consider the AOT to be a hamartoma, but certainly there is no evidence that these lesions stop growing. As they are known to achieve a size of several centimeters and to involve the whole maxillary sinus and even the skull base, the removal does need to be thorough along with any significantly involved teeth. 47,52,53
Keratocystic Odontogenic Tumor
Definition
(ICD-O code 9270/0)
A benign intraosseous tumor of odontogenic origin, keratocystic odontogenic tumor (KCOT) may be unicystic or multicystic. It is a potentially aggressive, infiltrative lesion composed of parakeratinized stratified squamous epithelium. The multiple lesions may be associated with nevoid basal cell carcinoma syndrome (NBCCS).
Etiology
Recent studies have described the role of the human homologue of the Drosophila patched gene (PTCH) tumor suppressor gene in KCOT. Somatic mutations of the PTCH gene have been reported in sporadic odontogenic keratocysts as well as those associated with the nevoid basal cell carcinoma syndrome.54–56
Synonyms
An important and long-standing synonym is odontogenic keratocyst (OKC), a term introduced by Philipsen in 1956.54 This widely used synonym suggests a benign process, but the WHO working group reclassified this lesion as KCOT in 2005 as that better reflects its neoplastic aggressive nature.5 Other synonyms include primordial cyst, epidermoid cyst of the jaws, cholesteatoma of the jaw, and odontogenic keratocystoma.
Incidence and Site
There is a ratio of ~2:1 of keratocysts occurring more frequently in the mandible than maxilla. The prevalence within all odontogenic lesions varies considerably depending on the age of the literature and the understanding at the time of these different entities. Figures up to 16.5% have been noted.57 In the maxilla, the commonest site appears to be in the region of the canine tooth. Bearing in mind the time at which this substantial publication was written, Brannon (1976) reported 312 cases with the age of the patients ranging from 7 years to 93 years.58
The mean age of patients with multiple KCOTs, with or without the NBCCS, is lower than that of those with single KCOTs. There appears to be a slight preponderance in males. Briefly, the NBCCS was first described by Gorlin and Goltz in196059 and is characterized by (1) basal cell carcinoma at an early stage, (2) multiple odontogenic keratocysts in the jaws, (3) broad nasal base, (4) frontal and parietal bossing, (5) calcification of the falx cerebri, (6) bifid ribs and other skeletal abnormalities, (7) palmar and plantar pits. It is of autosomal dominant inheritance with marked penetration and odontogenic keratocysts are present in over 65% of these patients. Multiplicity of the cysts is common and, within the upper jaw, the second molar region is the commonest site of occurrence. Recurrence in the older literature is extremely common, with figures of up to 85%.60
Multiple odontogenic keratocysts have also been reported in association with Marfan′s and Noonan′s syndromes.61,62
Diagnostic Features
Clinical Features
As with other odontogenic lesions, presentation within the maxilla is often a painless swelling that may enlarge to involve the face and produce nasal obstruction if the tumor enlarges further. Cases have been described displacing the lateral wall of the nose, destroying the anterior wall of the maxilla, and extending as a soft tissue cystic swelling up to the medial canthus. Lesions may be associated with loosening of the teeth and may reach a large size prior to presentation.62 If these larger cysts are opened then they are found to contain foul-smelling cheesy material not unlike cholesteatoma, hence some of the previous synonyms.
Imaging
KCOTs are generally well defined with sclerosis around mono- or multicystic areas. They may be related to an impacted tooth or root apex with considerable adjacent expansion of the upper jaw. Radiographically, they may be indistinguishable from a dentigerous cyst, a lateral periodontal cyst may cause divergence of tooth roots but rarely resorption (Fig. 12.2).
Histological Features
The KCOT has a distinct histological appearance, the cyst being lined with a thin layer of parakeratinized stratified squamous epithelium usually around 5 to 7 cells thick. The lumen is usually filled with keratin. Because of the lack of rete ridges, the cyst′s lining frequently separates from the underlying cyst wall and this overall structure is one of the explanations for the recurrence of this lesion because as the cyst′s lining is extremely thin, it is readily torn at the time of surgery. The basal layer is hypochromatic and exhibits prominent palisading of the basal cells. Secondary inflammatory changes may be present and, importantly, “daughter cysts” and proliferative odontogenic epithelium may be seen in the wall, suggesting the possibility of the NBCCS. These daughter and satellite cysts are another reason why the lesion may be incompletely removed. Cellular atypia and mitosis are said to be uncommon, but cyst lining left in situ will rapidly regrow. 63
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