Adenomotoid odontogenic tumor

Adenomatoid odontogenic tumor

Terminology and History:

Earliest publication of AOT was by Steensland, Dreybladt, James and Forbes, L’Esperance and Stafne in the year 1905 as "epithelioma adamantinum''

According to Philipsen and Reichart, Stafne was the first author to consider AOT as a separate entity. Although, Stafne did not propose a specific term for the lesion, he reported a series of three cases under the title “Epithelial tumours associated with developmental cysts of maxilla"

Terminologies used:‘‘cystic adamantoma’’, ‘‘adenoameloblastoma’’, ‘‘cystic complex composite odontoma’, “tumor of enamel organ epithelium”, “glandular ameloblastoma” ‘‘ameloblastic adenomatoid tumour’’, ‘‘odontogenic adenomatoid tumour’’, “pseudo-adeno adamantinum” & “pleomorphic adenoma –like tumor”

Philipsen and Birn introduced the term adenomatoid odontogenic tumour, to be adopted by the WHO in their ``Histological Typing of Odontogenic Tumours, Jaw Cysts and Allied Lesions'' in 1971

Histological Definition:

"A tumour of odontogenic epithelium with duct-like structures and with varying degrees of inductive change in the connective tissue. The tumour may be partly cystic, and in some cases the solid lesion may be present only as masses in the wall of a large cyst. It is generally believed that the lesion is not a neoplasm"

-WHO Histological typing of odontogenic tumors,1992

Histologically AOT may present as a cystic or solid lesion as stated in the WHO definition, but very few cases with cystic presentation have been reported. Whether AOT is truly cystic, neoplastic in origin or a hamartoma remains a matter of controversy

Clinical variants:(i)Pericoronal/Follicular (ii)Extracoronal/Extrafollicular (iii)Peripheral

 Clinical and radiographic definitions:

The AOT is a benign (hamartomatous), non-invasive lesion with a slow but progressive growth. It occurs in intraosseous as well as in peripheral forms .. Radiographically, the intrabony variants comprise a follicular and an extrafollicular type.

 The follicular type shows a well-defined, unilocular (round or ovoid) radiolucency associated with the crown and often part of the root of an unerupted tooth thus mimicking a dentigerous or follicular cyst. In fact, 77% of follicular type AOT are initially diagnosed as dentigerous cysts .

 The extrafollicular type is, on the other hand, not associated with an unerupted tooth and the welldefined, unilocular radiolucency is found between, above or superimposed upon the roots of erupted, permanent teeth. These locations often lead to the preoperative, tentative diagnosis of a residual, radicular, `globulo-maxillary' or lateral periodontal cyst depending on the actual intraosseous site of the lesion . In approximately two-thirds of the intrabony variants the radiolucency shows discrete foci having a flocculent pattern of scattered radiopacities. If the AOT contains minimal quantities of calcified deposits, intraoral periapical radiographs are superior to panoramic radiographs in detecting the characteristic (although not pathognomonic) radiopacities . Growth of the intrabony variants commonly results in cortical expansion. Displacement of neighbouring teeth due to tumour expansion is much more common than root resorptions. 

The peripheral variant appears as a gingival fibroma or epulis attached to the labial gingiva. This type of AOT may show slight erosion of the alveolar bone crest but radiographic changes are often diffcult to detect.

Clinical Features:

Age:Can affect from 3-82 years.Peak incidence is during 2nd decade especially during the teens

Gender:Female : Male ratio-2:1

Site:Mostly canine region

Why AOT is called 2/3rd  tumor?

2/3rd of adenomatoid tumors occur in the maxilla, 

2/3rd occur in young females, 

2/3rd of the cases are associated with un-erupted teeth,

2/3rd of the affected teeth are canines

Histogenesis:

Histogenetically the specific stimulus that triggers proliferation of the progenitor cells of AOT is unknown . However, various school of thoughts have been put forward from time to time. Due its exclusive occurrence within the tooth-bearing areas of the jaws (associated closely with an unerupted or impacted tooth)

 Philipsen et al have strongly suggested that the AOT arises from remnants of the successional dental lamina or the accessional dental lamina. 

According to Hodgson and as elaborated by Reichart and Philipsen, the odontogenic epithelial rests are not distributed haphazardly but are confined to the gubernaculum dentis. Theoretically, the eruption of a permanent tooth/teeth adjacent to an odontogenic tumor may be halted when the tumor envelopes the crown of the tooth and disrupts the gubernaculum dentis, also where the developing tooth erupts into a hamartomatous or neoplastic mass, the guiding influence of the gubernaculum dentis is lost. Hence, a pericoronal lesion associated with an unerupted tooth is formed. Similarly, if the odontogenic tumor were to arise from epithelial rests outside the eruptive path, eruption of the adjacent tooth/teeth would not be impaired and, following normal eruption, the tumor would be located lateral, or possibly even apical, to the erupted tooth/teeth .

  Bhaskar was of the view that AOT is a follicular cyst with intracystic proliferation derived from outer enamel epithelium .

 Spouge suggested origin from preameloblast cells found in the cervical region of inner enamel epithelium, prior to induction of odontoblast & before deposition of enamel matrix . This view was substantiated by Tagaki ultrastructurally. Association of the tumor with well-formed embedded teeth would suggest a possible origin from the REE (reduced enamel epithelium) surrounding the crown or from the epithelial lining of the cystic cavity . With the formation of tumor the lining may have encircled the whole tooth within it. So, the development of AOT from epithelial remnants present in the gubernaculum dentis can give a unified concept or better explanation as far as histogenesis is concerned in most cases of AOT

Pathology:

Macroscopic:The intrabony AOT variants are roughly spherical in shape with a well-defined fibrous capsule. The cut surface may reveal a solid tumour mass or show one large or several small cystic spaces containing a yellowish, semi-solid material. In the follicular type a crown and often part of the root of an unerupted tooth is found embedded in the tumour mass or projecting into a cystic cavity.

Microscopic:At low magnification the most striking pattern is that of varying sized solid nodules of cuboidal or columnar epithelial cells forming nests or rosette-like structures with minimal stromal connective tissue.

 Between the epithelial cells of nodules and in the centre of the rosette-like configurations, eosinophilic amorphous material (often described as ``tumour droplets'') are present.

 Spindle-shaped or polygonal, closely opposed epithelial cells with dark, eosinophilic cytoplasm and round hyperchromatic nuclei fill in the spaces between the epithelial nodules. 

Conspicuous within the cellular areas are structures of tubular or duct-like appearance. The duct-like spaces are lined by a single row of low columnar epithelial cells, the nuclei of which are polarized away from the luminal surface lumen may be empty or contain a variable amount of eosinophilic material or cellular debris. The ducts vary considerably in diameter and may not always be present. However, due to the overall distinctive histomorphology of the AOT, the diagnosis can usually be secured without the presence of duct-like structures. In addition to forming ducts, the cuboidal to columnar cells form convoluted cords or bodies in complicated patterns often showing invaginations.

 Another cellular pattern is nodules composed of polyhedral, eosinophilic epithelial cells of squamous appearance exhibiting well-defined cell boundaries and prominent intercellular bridges. Their nuclei may occasionally show very mild (degenerative) pleomorphism. These islands may contain pools of amorphous amyloid-like material and globular masses of calcified substances. Occurrence of one or several nodules of this cellular arrangement in AOT has led a number of authors to suggest the existence of a socalled combined AOT/calcifying epithelial odontogenic tumour (CEOT) lesion. However, the presence of CEOT like foci within an AOT does not influence its biological behaviour and growth potential. CEOT-like areas occurring in AOTs should be considered a normal feature within the continuous histomorphological spectrum of AOT.

Another epithelial pattern is found between and connecting the cell-rich nodules and, in particular, at the tumour periphery. It is composed of strands of epithelium, one to two cells in thickness, forming a trabecular or cribriform configuration.

Induction of hyaline, dysplastic dentinoid material or calcified osteodentin has been described by several authors.

The connective tissue stroma of AOT is generally very loosely structured and contains thin-walled congested vessels characteristically showing marked degenerative (fibrinoid) changes of the endothelial lining, vessel wall and perivascular connective tissue.

Ultrastructural findings 

Identical histology of all variants 

 The epithelial nature of the AOT has been confirmed through the finding of well developed gap junctions, desmosomes and desmosomelike junctions. Tight junctions have, however, not been described. Tonofilaments are present in varying amounts. 

Three ultrastructurally different types of epithelial tumour cells have been recognized corresponding to the three cell populations seen in light microscopy . The material found in the duct-like spaces has a granulo-fibrillar appearance. This material is separated from the adjacent tumour cells by a basal lamina-like zone, a finding lending support to earlier theories suggesting the `ducts' to be formed as a result of degeneration of the stromal tissue.

 Hemidesmosomes are found between the cells and this matrix. Tumour cells demonstrating squamous cell metaplasia (representing CEOTlike areas) are polygonal, contain an abundance of tonofilament bundles and possess well-formed desmosomes. 

El-Labban  reported that the eosinophilic amorphous masses are heterogeneous and consist of three types of fibrils: thin collagen fibrils, electron-dense fibrils and amyloid filaments. 

A recent study  has disclosed that the most conspicuous feature of the amorphous (non-calcified) eosinophilic material (`tumour droplets') is concentrically arranged tubular structures, the surface of which may be coated by a fine granular material. The authors suggested that the tumour droplets most probably represent some form of enamel matrix.

CYST, TUMOR OR HAMARTOMA

 Whether AOT is a cyst, tumor or a hamartoma is still a matter of debate. Some authors consider it as a true benign, non-aggressive, non-invasive neoplasm while others consider it as a hamartomatous odontogenic growth. In the recent past, certain authors preferred calling it as a cyst because on histopathologic examination they found a cystic lumen, lining and connective tissue capsule.

 Marx & Stern proposed the term adenomatoid odontogenic cyst and considered it to be a cyst, that has a hamartomatous intraluminal proliferation of epithelial cells derived from Hertwig’s epithelial root sheath & these cells fill the lumen & give the impression of a solid tumor . The various possibilities related to the nature of AOT being a tumor, hamartoma or cyst are discussed as follows: 

AOT as Hamartoma:

 Hamartomas represent a dysmorphic proliferation of tissue that is native to the area and does not have the capacity for continuous growth but merely parallels that of the host. The distinction between a hamartoma and a benign neoplasm is often arbitrary . 

Most author’s consider it as a hamartoma due to

 a) Limited size in most cases (attributed to its minimal growth potential)

 b) The lack of recurrence (even following definitely incomplete removal) 

c) Occurence in tooth bearing area & histopathologically resemblence to enamel organ.

 AOT as Benign neoplasm:

 Benign neoplasms also are dysmorphic proliferations of tissues, but they have the capacity for continuous autonomous growth. These neoplasms will continue to proliferate, albeit slowly in most cases, unless completely removed . AOT is also considered as a nonaggressive, noninvasive benign neoplasm because 

a) Some authors believe that the limited size of most cases stems from the fact that most cases are detected early and removed before the slow-growing tumor reaches a clinically noticeable size .

 b) They also point to the considerable size of some reported cases that had gone undetected or untreated for many years and resulted in facial asymmetry and distortion .

 c) Histologically, the lesion shows greater deviation from the arrangement of the normal odontogenic apparatus than should be expected in a developmental anomaly .

 d) Few cases of recurrence have been reported in the literature . 

Further, reviewing the literature revealed that features were both in favour of it being a hamartoma and tumor. Therefore, to regard it either as a hamartoma or a tumor is justifiable. 

AOT as Cyst

 Regezi et al. described AOT as an intracystic epithelial proliferation composed of polygonal and spindle cells.

 Marx and Stern proposed that AOT is not a tumor, rather a cystic lesion in which intraluminal proliferation occurs and hence, proposed the term “Adenomatoid odontogenic cyst” (AOC) .

 In the past, few cases had been reported describing AOT as a cyst. 

Cystic presentation of AOT was first described by Harbitz in 1915 who reported the lesion as ‘‘cystic Adamantoma’’ . 

The systematic review of literature of AOTs associated with or originating from an odontogenic cyst and reported primarily as cystic AOT, has shown that most of the lesions described in the past lacked the clear description of the lining epithelium and the photographic evidence . Some cases mentioned the cystic appearance on gross examination but didn’t describe the histopathology .. Few lesions which were described as cystic, were basically hybrid tumors and associated with COC (calcifying odontogenic cyst) & Unicystic ameloblastoma. Very few authors in their case reports have histologically described the cystic lining as non-keratinized, stratified squamous of 2-4 cell thickness, but elaborate description was missing. . 

Treatment :

Since all variants of AOT show an identical, benign biological behaviour and since they in almost all reported cases are well encapsulated, conservative surgical enucleation or curettage has proven the treatment modality of choice