KLINIČKE I RADIOGRAFSKE ODLIKE ADENOMATOIDNOG ODONTOGENOG TUMORA CLINICAL AND RADIOGRAPHIC FEATURES OF ADENOMATOID ODONTOGENIC TUMOUR

Uvod:Adenomatoidni odontogeni tumor (AOT) je neuobičajeni, neagresivni tumor poreklom od odontogenog epitela. On čini 3-7% svih odontogenih tomora. Cilj ovog članka bio je da utvrdi trenutne mogućnosti kliničkog i radiografskog ispitivanja odlika AOT. Koristeći odgovarajuće ključne reči, pretražili smo obilnu literaturu PubMed baze podataka u poslednjih deset godina. Od 57 članaka o AOT, 35 je imalo studijske kriterijume i oni su uključeni u pregled. Rezultati pokazuju da je najčešće mesto pojave AOT u posteriornim delovima mandibule, što je u suprotnosti sa postojećim podacima iz literature, prema kojima se tvrdi da se AOT najčešće pojavljuje u anteriornom regionu maksile. Ovaj članak daje korisne informacije parteći demografske, kliničke, radiografske i histološke odlike AOT.


Introduction
Adenomatoid odontogenic tumour (AOT) is an uncommon, non-aggressive tumour of the odontogenic epithelium 1 .It was first described by Dreibladt 2 in 1907 as pseudo adenoameloblastoma and later by Harbitz 3 in 1915 as cystic adamantoma.Philipsen and Birn 4 in 1969 suggested that it should not be considered as ameloblastoma due to its different clinical behaviour and proposed the term 'adenomatoidodontogenic tumour'.WHO in 2005 defined AOT as 'a tumour composed of odontogenic epithelium presenting a variety of histoarchitectural patterns, embedded in a mature connective tissue stroma and characterised by slow but progressive growth 5 .
The tumour is sometimes referred to as'two-thirds tumour' because it occurs in the maxilla in about 2/3 of the cases, about 2/3 of the cases arise in young females, 2/3 of the cases are associated with an unerupted tooth, and 2/3 of the affected teeth are the canines 6 .

Methodology
A comprehensive literature search of the PubMed database with terms such as 'adenomatoid odontogenic tumour', 'AOT', 'radiographic feature' and 'impacted tooth' was conducted from 2005-2014.Fifty seven articles were identified in the preliminary database search, among which 35 met the inclusion and exclusion criteria Table 1.Patient demographics, clinical, radiographic and histopathologic information were obtained from these records and are presented in Table 2 2, . The ocation of the cyst was considered as incisor, canine, premolar, molar and retromolar areas.When the lesion extended to more than one area, the central part of the lesion was considered as the affected site.

Tabela 1. Tabela prikazuje kriterijume uključivanja i isključivanja
Table 1.The radiographic features of the case must be mentioned along with the presence or absence of an impacted tooth Radiografske odlike slučaja moraju biti pomenute u okviru prisustva ili odsustva impaktiranog zuba The histological features of the lesion must be confirmatory of AOT

Discussion
The adenomatoid odontogenic tumour is a benign, slow growing, non-invasive odontogenic lesion that accounts for 3%-7% of all odontogenic tumours 2 .The origin of AOT is controversial with some authors claiming it to be a hamartoma 6 .However, most authors accept its odontogenic source as it occurs within the tooth bearing areas of the jaws and is often found in close association with impacted teeth.There is evidence that the tumour cells are derived from enamel organ epithelium; investigators have also suggested that the lesion arises from remnants of dental lamina 27 .As the histogenesis is still uncertain, there has long been a debate as to whether it represents a hamartomatous growth or a true benign neoplasm, having cytological features similar to various components of enamel organ, dental lamina and reduced enamel epithelium 6 .The characteristic features of this lesion are due to both the highly differentiating ability of the epithelial component and the lack of mesenchymal tissue receptive to the influence of the epithelium 1 .pacijenata koji imaju preko 30 godina.Žene su češće pogođene od muškaraca u odnosu 1,9:1 37,38 .Batra i sar 2 otkrili su da je 69% AOT dijagnostikovano u drugoj deceniji života, a više od polovine slučajeva javlja se u tinejdzerskom periodu.U prisutnoj analizi utvrđeno je da je starost pacijenta između 9 i 46 godina sa srednjim dobom od 19 godina.Prijavljeno je 22 slučaja u drugoj dekadi života i samo jedan (2,8%) slučaj u petoj deceniji života.Na ženski pol (71,4%) odnosi se dvadeset pet slučajeva dok su desetorica bili muškarci (28,5%), što ukazuje na odnos 2,5:1.
Martinez A et al. 19 stated that AOT is usually encountered in young patients, usually in the second decade of life and is uncommon in patients over 30 years of age.Females are affected more often than males with a female to male ratio of 1.9:1 37,38 .Batra et al. 2 found that 69% of AOTs were diagnosed in the second decade of life and more than half occur during the teenage years.In the present analysis, it was seen that the age of the patients ranged from 9 to 46 years with a mean age of 19 years.Twenty two (62.8%) of the cases were reported in the second decade of life and only 1 (2.8%) case was seen in the fifth decade.Twenty-five of the cases affected females (71.4%), while 10 were males (28.5%) bringing the female to male ratio to 2.5:1.
The lesion is seldom more than 3 cm in size and has a striking tendency to occur in the anterior portions of the jaws.It is found twice as often in the maxilla as in the mandible 7,19 .Leon et al. 39 in their study of 39 cases of AOT found that anterior maxilla is the commonest site.
However, among the 35 cases that were considered in the present review, 19 cases affected the mandible (54.8%) while 16 cases affected the maxilla (45.7%).In the mandible, the posterior region was affected in 57.8% of the cases while the anterior region was affected in 42.1% of cases.In the maxilla, topographical division showed that the anterior region was the most commonly affected site with a frequency of 93.7% while the posterior region showed the least affinity for AOT (6.2%).Thus, according to the present review results posterior mandible is the predominant site of occurrence.This is contrary to the existing literature data 13, 15, 16, 19, 39.This result may be due to the following reasons: either it is a true indication of the recent trend in occurrence of AOT, or it is a reflection of publication bias wherein only cases which show a rare presentation are being published.Underreporting of cases of AOT occurring in the maxillary anterior region may be another cause.
AOT can occur both intraosseously and extraosseously 27 .Intraosseous AOT occurs as an expansile growth and can be radiographically divided into two types: follicular (pericoronal) and extrafollicular Ekstraosealna AOT se prezentuje kao sesilna masa na gingivi 27 .
(extracoronal).Friedrich et al. 20 found that the follicular variety is by far the most frequent type of AOT.It usually appears as a pericoronal well circumscribed unilocular radiolucency or radiopaque-radiolucent mixed lesion with well-defined corticated or sclerotic border, usually surrounding an unerupted tooth while the extra-follicular variant presents as a well-defined unilocular radiolucency located between, above or superimposed on the root of a tooth 6 .Extraosseous AOT presents as a sessile mass on the facial gingiva 27 .
The usual radiographic appearance of AOT is a well-defined radiolucency with a corticated or sclerotic border at the cuspid region of maxilla.Displacement of adjacent teeth is seen but root resorption is rare 1 .Of the 35 cases taken up for analysis, root resorption of the adjacent teeth was seen in 6 (17.1%) cases.It was noted that there was an associated impacted tooth in 65.7% of the cases.Batra et al. 2 reported that impacted canines accounted for 59% of the cases.Similarly, in the present study, it was found that among the teeth that were impacted, canine showed the highest prevalence (82.6%), while premolar was associated in 13% of the cases and incisors, molars and supernumerary teeth showed minimal prevalence at 4.3%.AOTs may contain multiple minute variably shaped radiopaque foci or calcifications which may appear as a cluster of pebbles or may show fine snowflake like calcifications 27 .These calcified deposits are seen approximately in 78% of the cases 40,41 .Intraoral periapical radiograph is the indicated radiograph for the detection of calcifications.From Table 2, it is seen that AOT presented as a unilocular radiolucency in 18 (51.4%) of the cases, while radiopaque flecks of calcified material were seen in 14 (40%) of the reported cases.Only 2 (5.7%) cases presented as a multilocular radiolucency with radiopaque foci.
Generally, the radiographic differential diagnosis of an AOT includes dentigerous cyst, calcifying odontogenic cyst, calcifying epithelial odontogenic tumour, uniloculara-meloblastoma and keratocystic-odontogenic tumour.In some cases, lateral periodontal cyst and keratocystic odontogenic tumour can be considered in the diagnosis.Macroscopically, AOT is a well-defined lesion surrounded by a thick fibrous capsule.
Microscopically, the tumour is composed of spindle-shaped epithelial cells that form sheets, strands or whorled masses in a scant fibrous stroma.The epithelial cells may form rosette-like structures about a central space 42   .The characteristic duct-like structures are lined by single layer of columnar epithelial cells, the nuclei of which are directed away from the central lumen 37 .The mechanism of formation of these tubular structures may be a result of the secretory activity of the cells which appear to be preameloblasts 38 .The lumen may be empty or may contain small amounts of eosinophilic material that may stain for amyloid.Small foci of calcification may be seen scattered throughout the lesion which have been interpreted as abortive enamel formation, dentinoid material or cementum 27 .
Analysis of the histopathological features of the 35 cases revealed that the lesions showed whorles, sheets, and plexiform arrangement of cells with rosettes of spindle-shaped epithelial cells surrounding the ductal architecture.Amorphous eosinophilic amyloid and hyaline-like material with dystrophic areas of calcification were seen in 25 (71.4%) of the cases.Deposits of enamel matrix with the overlying dentin was seen in 4 (11.4%) of the histologic sections.
Immunohistochemistry studies of the lesions suggest the expression of keratin and vemintin in the tumour cells at the periphery of the ductal, tubular or whorled structures 43 .Amelogenin and enamelin in small mineralised foci are found in the tumour cells and in hyaline droplets 44 .
Since all variants of the tumour show encapsulation, surgical enucleation or curettage is the treatment of choice 2 .A recurrence rate of 0.2% has been reported 32 .If the follicle is found to be uninvolved during surgery, it may be possible to remove the lesion while leaving the tooth in place, especially in cases of involvement of the maxillary canine in young patients 2 .A long term follow-up of the patient is recommended.Our review was in accordance with the existing literature of AOT regarding the age, sex, radiographic presentation, and histopathological features.However, we found highest predilection for AOT in the mandibular posterior region.This contradicts the existing literature where the maxillary anterior region is the common site of involvement.

Conclusion
1.AOT is a benign, slow growing, non-aggressive odontogenic tumour.Our systematic review revealed that AOT was most frequently seen in females and in the second decade of life and was rare in older individuals after the fifth decade.The commonest site of occurrence was the mandibular posterior region.It was found that AOT usually presents as a unilocular radiolucency causing resorption or displacement of the adjacent roots.An impacted tooth, usually a canine was found in a majority of the cases.Thus, this review of AOT compiles the recent literature regarding the demographic parameters, clinical, radiographic, and histological features.
Table with the inclusion and exclusion criteria