Oral Oncol, EurJ Cancer, Vol. 29B, No. 3, pp. 221-224, 1993

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Adenomatoid Odontogenic Tumour with Features of Calcifying Epithelial Odontogenic Tumour. (The so-called Combined Epithelial Odontogenic Tumour.) Clinico-pathological

Report of 12 Cases

Constantino Montes Ledesma, Adalberto Mosqueda Taylor, Elias Romero de Le6n, Mario de la Piedra Garza,

Paul Goldberg Jaukin and Javier Portilla Robertson

The combination of two odontogenic tumours is a rarely reported finding. To date only 10 cases of adenomatoid odontogenic tumour (AOT) combined with areas of calcifying epithelial odontogenic tumour (CEOT) have been published. This article describes the clinical, radiographical and micro- scopic findings of 12 cases of AOT, in which CEOT-like areas of variable sizes were found. These results suggest that such areas may be considered as a normal feature within the histomorphological spectrum of AOT. Oral Oncol, Em3 Cancer, Vol. 29B, No. 3, pp. 221-224, 1993.

INTRODUCTION ADENOMAT-OIDODONTOGENICTUMOUR (AOT)isanodon- togenic epithelial tumour first described as a distinct entity by Stafne in 1948 [l]. Clinically, it usually appears as an asymptomatic, slow growing swelling associated with an unerupted tooth. It is seen more frequently in female patients and occurs most frequently during the second decade of life. Radiographically it appears as a well defined radiolucent area in which a variable amount of radio-opaque mineralised mat- erial can occur [2]. The microscopic features include the pres- ence of ductiform structures formed by a single row of cuboidal or low columnar cells. Nodules of spindle-shaped or cuboidal cells forming sheets or rosette-like structures are found surrounding the ductiform areas. In addition, droplets of eosinophilic amorphous material, sometimes with evidence of mineralisation can be detected between the epithelial cells. A trabecular or microcystic pattern formed by round or spindle-shaped cells is found at the periphery of the lesion [3].

Calcifying epithelial odontogenic tumour (CEOT) was first described by Pindborg in 1955 [4]. It has a peak incidence at around 40 years of age, with no sex or racial predilection and

Correspondence should be addressed to A. Mosqueda T., Departa- mento de Atencion a la Salud, Universidad Autonoma Metropolitana- Xochimilco, Calzada de1 Hueso 1100, Col. Villa Quietud, M&co, D.F. 04960, M. C.M. Ledesma, M. de la Piedra Gana and J.P. Robertson are at the Facultad de Odontologia, Universidad National Autonoma de Mexico, Ciudad Universitaria, Mexico, D.F. 045 10; E.R. de Leon is at the Facultad de Odontologia, Universidad Autonoma de Nuevo Le6n, Monterrey, N.L. Mexico; and P.G. Jaukin is at the Facultad de Odontologia, Universidad Intercontinental, Insurgentes Sur 4 135, Mexico, D.F. Received 11 Nov. 1992; accepted 25 Nov. 1992.

its main location has been the mandibular molar region [5]. Radiographically it appears as an ill-defined radiolucent area in which mineralised structures of varying size may be present. Approximately half of the cases have been associated with an unerupted or embedded tooth, or teeth [5,6].

Microscopically this tumour is composed of sheets or strands of polyhedral epithelial cells with eosinophilic cyto- plasm, well-defined cell borders and distinct intercellular bridges. Cellular pleomorphism and prominent nucleoli are frequently found, but mitoses are rarely seen. The presence of extracellular, acidophilic homogeneous material which fre- quently calcifies and may form Liesegang rings is a common finding. Special staining techniques, particularly thioflavine T, show that this homogeneous material reacts in a similar way to amyloid [6].

In 1982 Damm et aZ. [7] made the first description of the presence of CEOT-like areas within two cases of AOT, and named these as combined epithelial odontogenic tumour. Later, four additional reports of one case each were published by Bingham and Adrian [8], Takeda and Kudo [9], Siar and Ng [lo] and Okada et al. [l 11. Recently Siar and Ng [ 121 reported a series of 5 cases (including their previously reported one), which makes a total of 10 cases published up to date in English (Table 1).

MATERIALS AND METHODS A total of 15 cases of AOT were retrieved from the files of

three Oral Pathology Services of the Faculties of Dentistry of three different Universities in Mexico (Universidad National Autonoma de Mexico, Universidad Autonoma Metro- politana-Xochimilco and Universidad Autonoma de Nuevo Leon). All cases were reviewed to detect the presence of CEOT-like areas within the tumours. Additional sections

221

222 C.M. Ledesma et al.

Table 1. Combined epi&&zl odonwgenic tumour. Reported cases

Reference Year Age Sex Race Location RX image Treatment Follow-up

7 1983 18 M White Interradicular

1983 15 F

8 1986 14 F

9 1986 17 F

10 1987 28 M

11 1987 27 F

12 1991 13 M

1991 14 F

Black

Black

Japanese

may

Japanese

Indian

Malay

43-44 Pencoronal 47 Pericoronal 44 Interradicular 21-22 Pencoronal 13 Pericoronal 18 Pericoronal 22-23 32-33 (Residual cyst) 24-28 Pencoronal 33-35

RLwithRO

RLwithRO

RL

RLwithRO

RL

RLwithRO

RL

NA

Enucleation

Subtotal cystectomy

Cystectomy

5 years, No ret

1 year, No ret

Enucleation

Enucleation

Enucleation

Enucleation

Enucleation

2 years, No ret

1 year, No ret

9 years, No ret

NA

11 months, No ret

27 months, No ret

1991 22 F 1991 28 F

Chinese NA RL

Enucleation Enucleation

34 months, No ret 1 year, No ret

NA = not available; RL = radiolucency; RO = radio-opacities.

were carried out for those cases in which this structure was not found in order to discover the true incidence of this particular feature. All slides were stained with haematoxylin and eosin, and those with areas suggestive of CEOT were stained with Congo Red and were examined under polarised light search- ing for the presence of amyloid material.

RESULTS On the original slides, 10 AOT cases showed CEOT-like

areas of varying size. Of the remaining 5, only 2 had tissue available to obtain additional sections, both of which showed this finding. Unfortunately no paraflin blocks were available in the remaining 3 AOT cases, and for this reason they were not included in the study.

Clinical findings Sex distribution disclosed 10 cases occurring in females

(83%) and 2 in males (17%). The main clinical findings are summarised in Table 2. The age range was between 10 and 21 years, with a mean of 15.8 years. 9 cases were located in the maxilla (75%) and 3 in the mandible (25%). In 10 cases

the lesions were located within the incisive-canine region and 2 in the premolar area.

All cases were asymptomatic, except for 1 that showed superficial ulceration of traumatic origin. 6 cases presented as tumoral growths, while the remaining 6 were detected on radiographical examination.

11 cases were intraosseous, with 10 of them found in a follicular (dentigerous) relationship and one as extra-follicular type according to the classification of Philipsen et al. [3]. It is interesting to note that the remaining case had an exclusively peripheral location in the maxillary canine gingiva, a finding which has not been previously reported for combined AOT-CEOT. Radiographical examination obtained from the clinical data provided with the biopsy specimens stated that all central cases were well-defined radiolucent lesions, 5 of which were referred to as having internal opacities. The most frequently involved tooth in the follicular lesions was an unerupted canine (in 7 cases). The lateral incisor and first and second premolar were associated each in 1 case. The extrafollicular case appeared as a periapical lesion related to an upper canine.

Table 2. Adenomawid oaknwfenic tumour with areas of calcifvinE epithelial odon~genic tumour. EYesent study

Case Age Sex Race Location

1 17 F 2 14 F 3 21 F 4 20 F 5 10 M 6 21 F 7 15 F 8 13 M 9 17 F

10 10 F 11 17 F 12 15 F

Mestizo Mestizo Mestizo Mestizo Mestizo Mestizo Mestizo Mestizo White White Mestizo Mestizo

Pericoronal 23 Pencoronal 13 Pencoronal 12 Periapical 23 Pericoronal 33 Gingiva 21 Pericoronal 43 Pericoronal 23 Pericoronal 23 Pericoronal 14 Pericoronal45 Pericoronal 23

RX image

RLwithRO RL RL RL RL

None RL

RLwithRO RLwithRO RL with RO RLwithRO

RL

Treatment

Enucleation Enucleation Enucleation Curettage Enucleation Local excision Enucleation Enucleation Enucleation Enucleation Enucleation Enucleation

Follow-up

11 years, No ret 8 years, No ret 5 years, No ret 2 years, No ret

2 years, No ret 1 year, No ret 6 months, No ret

9 years, No ret 10 months, No ret

6 months, No ret 1 year, No ret 2 years, No ret

RL= radiolucency; RO = radiopacities.

AOT with Features of CEOT 223

Fig. 1. AOT with two small foci of CEOT-lilte areas (arrows) near the fibrous capsule (C). Haematoxylin and eosin X 100.

All tumours were treated conservatively by surgical enuclea- tion, curettage or local excision, and their follow-up ranged from 6 months to 11 years with no evidence of recurrence in

any case (Table 2).

Macroscopic findings Follicular (dentigerous) cases appeared as smooth surfaced,

well circumscribed, round to ovoid, cystic sacs which in most cases were intact and surrounded the crown of the affected tooth. On section, they usually showed thick walls with small

whitish or yellowish granules or nodules projecting into the lumina. The extrafollicular lesion was obtained by curettage and consisted of numerous small irregular fragments of greyish-white soft tissue of variable sizes without evidence of cystic cavity. The peripheral tumour consisted of a 2 x 1 x 1 cm broad-based nodule covered by normal- appearing mucosa. On section, a small microcystic space was

found within the solid mass.

Microscopic findings All 12 cases showed the classical features of AOT, i.e. solid

nodules of spindle-shaped and cuboidal epithelial cells form- ing rosette-like structures which often contained intercellular droplets of eosinophilic material. In all cases a variable num- ber of ductiform spaces lined by a single row of cuboidal or low columnar cells was observed within the more cellular areas of the tumour and at the periphery, round to spindle-shaped cells formed a cribriform or trabecular configuration (Fig. 1). Cystic cases exhibited a thick fibrous connective tissue wall lined in some areas by a thin cuboidal epithelium compatible with reduced enamel epithelium.

CEOT-like areas of variable sizes were found in direct tran- sition from the spindle-cell population of AOT (Fig. 2). These foci consisted of sheets of polyhedral cells with eosinophilic cytoplasm of squamous appearance, and with most of the cellular features described for CEOT (Fig.3), including the production of a homogeneous, eosinophilic material which proved to be positive for amyloid on Congo Red stained sec- tions examined under polarised light, and the presence of mineralised laminated masses with formation of Liesegang rings (Fig. 4).

DISCUSSION It has been estimated that AOT accounts for approximately

2.9-6.8% of all odontogenic tumours [3], and that it is easily

Fig. 2. Detail of a transition zone of AOT-CEOT. Note large polyhedral epitbelial cells in association with numerous miner- alised bodies and surrounded by AOT spindle-shaped cells.

Haematoxylin and eosin x 200.

Fig. 3. Foci of CEOT-lihe cells showing abundant production of intercellular eosinophilic globules with varying degrees of

mineralisation. Haematoxylin and eosin x 400.

Fig. 4. CEOT-like area composed of polyhedral cells with large eosinophilic cytoplasm, well-defined cell borders, hyper- chromatic nuclei and numerous eosinophilic and mineralised

irregular bodies. Haematoxylin and eosin x 400.

224 C.M. Ledesma et al.

recognised by its classical histopathological features. At present, it is generally believed that this lesion is not a neo- plasm [6]. On the other hand, CEOT has been defined as a locally invasive epithelial neoplasm with a well-recognised histopathological pattern, characterised by the development of intraepithelial structures, probably of an amyloid-like nature, which may become calcified and liberated as the cells break down [6].

Although the presence of intratumoral nodules of CEOT- like epithelial cells has led some authors to consider these areas as true foci of CEOT [7- 121, it is important to note that such previously reported examples, as well as those presented here, have behaved as typical AOT cases, with no recurrence or aggressiveness.

The existence of nodules of variable size, composed of polyhedral eosinophilic cells which were very similar in appearance to CEOT within all our 12 AOT cases suggest that this is not an unusual finding. Instead, it seems to rep- resent a frequent histomorphological pattern of AOT, which must be recognised as such, in order to avoid considering it as an aggressive lesion.

Spindle-shaped cells in AOT appear to be morphologically and histochemically similar to stratum intermedium cells of the enamel organ [ 13, 141 which, according to some authors, is also the origin of CEOT cells [ 151. This could explain the co-existence of these two embryologically related cells within the most prevalent of the two lesions (AOT), which is usually identified by its characteristic ductiform and rosette-like arrangement of cells.

Our results suggest that those cases diagnosed as a combi- nation of AOT-CEOT are just examples of AOT in which the spindle-shaped cells of probable stratum intermedium origin have proliferated and formed foci of cells similar to CEOT, but without its local aggressiveness and infiltrative growth pat- tern. This conclusion is supported by the fact that most of the clinical and radiographical findings, and the behaviour of all the present cases as well as that of others reported, and so- called “combined epithelial odontogenic tumour” are basi- cally identical to those described for classic AOT. In addition there seems to be no reported cases of “combined epithelial odontogenic tumour” in which CEOT predominates over

AOT, which may possibly prove to be a true combination of two different odontogenic tumours.

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