CASE REPORT

A Combined Epithelial Odontogenic Tumor? A 7-Year Follow-Up
Case

Ana Cláudia Garcia Rosa1,2,6
• Andresa Borges Soares3

• Cristiane Furuse4
•

Sandro Régis Rodrigues Lima5
• Vera Cavalcanti de Araújo3

• Fabricio Passador-Santos3

Received: 16 August 2016 / Accepted: 31 October 2016 / Published online: 5 November 2016

� Springer Science+Business Media New York 2016

Abstract Adenomatoid odontogenic tumor (AOT) is a

benign epithelial odontogenic tumor characterized by slow

and progressive growth. When central lesions are associ-

ated with an unerupted permanent tooth, they are also

known as the follicular type. Histological variants of AOT

may complicate diagnosis with possible adverse effects on

treatment and prognosis. The aim of this study is to report a

case of a follicular AOT with extensive calcifying epithe-

lial odontogenic tumor (CEOT)—like histopathological

areas in the anterior region of the mandible that was treated

by enucleation. The teeth displaced by the tumor were

repositioned with orthodontic treatment, and after 7 years

of follow-up, the bone trabeculae were normal with no

evidence of recurrence. The clinical, radiographic and

histopathologic aspects of these tumors are discussed and

the debate surrounding whether these cases are true com-

bined lesions or histologic variants of the primary tumor is

raised.

Keywords Adenomatoid odontogenic tumor � Calcifying
epithelial odontogenic tumor � Congo red staining �
Odontogenic epithelium � Odontogenic tumors �
Orthodontic treatment

Introduction

Adenomatoid odontogenic tumor (AOT) is a benign

epithelial odontogenic tumor, first reported by Stafne in

1948 [1]. It accounts for 2–7% of all odontogenic tumors

and is characterized by its association with impacted teeth,

slow and progressive growth, affecting patients from young

age groups and low recurrence rates after treatment [2, 3].

AOT is predominantly asymptomatic and intraosseous,

with a preference for the maxilla over the mandible.

Intraosseous AOTs associated with an unerupted perma-

nent tooth characterize the follicular type of the tumor.

Calcifying epithelial odontogenic tumor (CEOT) is a

benign epithelial odontogenic tumor first described by

Pindborg in 1955 [4] and also referred to as Pindborg

tumor [5]. CEOTs account for approximately 1% of all

odontogenic tumors and their clinical behavior is different

from AOTs. They occur in patients aged around 40 years

[6] and have no gender predilection. When intraosseous,

they affect the mandible more than the maxilla with a

preference for premolar/molar regions, although any site

may be affected, with lesions being locally aggressive [7].

An association between AOTs and CEOTs has been

previously described by some authors [8–14], although

others consider that CEOT- like areas in AOTs are a his-

tologic variant [15–17].

Therefore, there is a lack of agreement in the literature.

Moreover, histologic variants of AOTs presenting similar

features to other odontogenic tumors or cysts may have

& Ana Cláudia Garcia Rosa

anaclaudiagarcia@ceulp.edu.br

1 Department of Oral Pathology, Lutheran University of

Palmas, Palmas, Tocantins, Brazil

2 Department of Health Sciences, Federal University of

Tocantins, Palmas, Tocantins, Brazil

3 Department of Oral Pathology, São Leopoldo Mandic

Institute and Research Center, Campinas, São Paulo, Brazil

4 Department of Oral Pathology, São Paulo State University,

Araçatuba, São Paulo, Brazil

5 General Public Hospital of Palmas, Palmas, Tocantins, Brazil

6 Faculdade de Odontologia, Centro Universitário Luterano de

Palmas—CEULP/ULBRA, Av. Teotônio Segurado, 1501

Sul, PO Box no 85, Palmas, Tocantins 77019900, Brazil

123

Head and Neck Pathol (2017) 11:519–524

DOI 10.1007/s12105-016-0767-9

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unspecific clinical and radiographic features that overlap

with those of other odontogenic tumors. These character-

istics reinforce the fundamental role of microscopic

examination in diagnosis, to ensure appropriate treatment.

The aim of this report is to describe a case of follicular

AOT in an unusual location, presenting extensive calcify-

ing epithelial odontogenic tumor (CEOT)–like areas, suc-

cessfully treated by surgical excision, extraction of the

associated canine, curettage of healthy bone margins and

repositioning of displaced teeth using a fixed orthodontic

appliance. Clinical, radiographic and histopathologic

aspects of the lesion are discussed based on a seven-year

follow-up period.

Case Report

The patient gave informed consent for inclusion in this

study. The authors have followed the Helsinki Declaration

guidelines of 1975, as revised in 1983.

A 17-year-old white female was referred with an

asymptomatic facial swelling in the anterior region of the

mandible causing a discrete asymmetry on the left side of

her chin. The lesion had been incidentally detected in a

panoramic radiograph taken for orthodontic purposes.

Intraorally, there was cortical expansion of the mandible

covered by normal mucosa associated with a missing

canine tooth and displacement of the crowns of adjacent

incisors and premolars. A panoramic radiograph showed a

well-defined unilocular radiolucent lesion containing fine

calcifications and the missing canine, all partially circum-

scribed by a radiopaque halo and displacement of the roots

of the neighboring teeth with no evidence of root resorption

(Fig. 1a). Needle aspiration of the contents of the lesion

yielded a clear fluid, which was compatible with a provi-

sional clinical diagnosis of dentigerous cyst (despite the

‘‘snowflake’’ appearance of the fine radiopaque dots). An

incisional biopsy was carried out, which revealed the

presence of a cystic space surrounded by a whitish fibro-

elastic capsule and smooth surface appearance containing a

transparent liquid material. A sample of the cystic wall was

removed and sent for microscopic examination.

Histopathological analysis showed a benign neoplasm of

odontogenic epithelium. At low magnification, the lesion

showed a thick fibrous capsule partially lined by a thin

epithelium. The capsule contained proliferating spindle,

cuboidal and columnar cells toward the lumen arranged as

nodules. There were rosette-like and rarely duct-like

structures lined by a single row of cuboidal and columnar

epithelial cells with the nuclei polarized to the basal side,

away from the luminal surface. Foci of eosinophilic

amorphous material and calcifications were present in

between epithelial cells. Mainly at the periphery, strands of

epithelium in a cribriform pattern were also observed.

(Fig. 2a–f). In a large part of the tumor, next to the nodules

located close to the capsule, there were polyhedral, eosi-

nophilic epithelial cells with a squamous appearance, with

distinct cell boundaries, prominent intercellular bridges and

occasional pleomorphic nuclei. Amyloid-like material and

calcifications were observed in between cells (Fig. 2a–d

and g). Congo red staining showed green birefringence

when subjected to polarized light in the cytoplasm of these

eosinophilic cells, in the amorphous hyaline material

between these cells and in the adjacent stroma (Fig. 2h).

Histopathological evaluation led to the diagnosis of an

AOT with CEOT–like areas.

The tumor was treated by surgical excision under local

anesthesia, including exodontia of the canine tooth and

vigorous curettage of bone margins. Clinical and radio-

graphic follow-up was performed periodically. Two years

later, the newly formed healthy bone trabeculae permitted

repositioning of the displaced teeth using orthodontic

treatment. The most recent follow-up record 7 years post-

operatively indicated no evidence of recurrence (Fig. 1b).

Fig. 1 a Conventional diagnostic panoramic radiography showing an

expansive, unilocular, radiolucent and well-delimited lesion in the

mandible, with radiopaque foci and peripheral bone condensation,

extending from the elements 41–36, involving the tooth 33 (arrow).

b Digital preservative panoramic radiography after 7 years of follow-

up, presenting the alignment of the teeth after orthodontic treatment,

normal trabecular bone formation and regional residual mandible

expansion

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Discussion

The microscopic features observed in the present case were

consistent with the diagnosis of an AOT with CEOT- like

areas, or the so-called combined epithelial odontogenic

tumor, an altogether unusual lesion. Authors elsewhere

have described odontogenic tumors with combined char-

acteristics of AOT and CEOT [8–14]. Such association

between tumors is questionable, however, as other authors

have considered them as usual histological variants of

AOTs [15–17]. In the most recent WHO International

Classification of Tumors, there is also a lack of consensus

regarding the grouping of this entity as an original com-

bined tumor or a histopathologic variant of AOT since both

have been described in the above-mentioned book [3, 7].

The histopathological analyses of the current case

revealed a lesion with the classical features of an AOT with

prominent CEOT-like areas, an unusual feature (Fig. 2a).

There were few pleomorphic cells, corroborating the

hypothesis that this is a variant type of AOT and not a true

combined tumor, although it was positive for Congo red

staining, a method admittedly used for the diagnosis of

CEOTs (Fig. 2h). In a multicentric study that analyzed the

largest series of AOT variants from a clinicopathological

Fig. 2 Histological sections. a and b AOT with extensive CEOT-

like areas. Note a thick fibrous capsule adjacent to AOT solid cell

nodules and CEOT- like areas located on the site opposite to the

capsule (HE, 940 and HE, 9100, respectively). c and d CEOT-like

areas close to AOT cell nodules (HE, 9100 and HE, 9200,

respectively). e and f Common AOT area with cubic or columnar

cells in solid arrangement forming rosette-like structures (HE, 9200

and HE, 9400, respectively). g Common CEOT-like area formed by

eosinophilic polyhedral cells with defined limits and calcifications

(HE, 9400). h Congo red staining under polarized light showing the

amyloid-like material in CEOT-like areas as a green birefringence

(940)

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viewpoint, only 10 of the 36 exceptional cases showed

positivity for Congo red under polarized light, with seven

cases limited to CEOT-like areas, as in this study [18].

Classically, AOTs are encapsulated tumors featuring

cuboidal or columnar epithelial cells forming solid nodules

of varying sizes in a scanty stroma of mature loose con-

nective tissue. The cells may be arranged in rosette-like

structures or in tubular structures that resemble ducts. The

ductiform structures are formed of a layer of columnar cells

with nuclei polarized to the side opposite to the lumen and

may contain eosinophilic material, which may also be

observed within the rosettes and between epithelial cells

along with calcifications. The cells may also form inter-

connected strands giving a cribriform appearance. Dys-

plastic hyaline material or calcified osteodentine may also

be present in varying amounts [3].

The variants that show CEOT-like areas are described as

tumors containing eosinophilic epithelial polyhedral cells

of squamous appearance, with evident intercellular bridges

and occasionally pleomorphic nuclei, amorphous amyloid

materials and globular masses of solid substances CEOT-

like [3]. Those who consider that these CEOT-like areas

are routine histopathologic findings of an AOT argue that,

in the microscopic areas compatible with the CEOT, the

epithelial cells lack the typical pleomorphism of a true

CEOT and tend to be confined to those areas of the AOT

that produce mineralized tissue [13, 14].

Radiographically, intraosseous AOTs appear as well-

defined unilocular radiolucent lesions around the crown or

root of a permanent tooth mimicking a dentigerous cyst,

which may also contain calcification foci [3]. Similarly,

CEOTs tend to appear as unilocular or multilocular radi-

olucent lesions with radiopaque deposits [7], sometimes

hindering a precise radiographic diagnosis between these

lesions. In the current case, the radiographic findings were

compatible with a classic follicular AOT with foci of cal-

cification (Fig. 1a).

The clinical behavior observed in this case also cor-

roborates the aforementioned hypothesis. The literature

regarding follow-up of AOTs with CEOT-like areas shows

that most such tumors exhibit the clinical features of a

conventional AOT, including localization to the maxilla

and a predilection for young females. Enucleation resolved

most of the lesions and all of them had a good clinical

outcome without recurrences (Table 1). Although these

lesions have been previously documented, to the authors’

Table 1 Identified cases of hybrid AOT-CEOTs (combined epithelial tumors) or AOT variants including CEOT-like areas with clinical data and

follow-ups in English literature

Case Author Entity as described Location Sex Age (years) Treatment Follow-up

1 Damm et al. [8] Hybrid AOT-CEOT Mandible M 18 Enucleation 5 y (NR)

2 Hybrid AOT-CEOT Mandible F 15 Excision 1 y (NR)

3 Bingham and Adrian [9] Hybrid AOT-CEOT Mandible F 14 Curettage 2 y (NR)

4 Takeda and Kudo [13] Hybrid AOT-CEOT Maxilla F 17 Enucleation 1 y (NR)

5 Siar and Ng [10] Hybrid AOT-CEOT Maxilla M 28 Enucleation 9 y (NR)

6 Siar and Ng [14] Hybrid AOT-CEOT Maxilla M 13 Enucleation 11 m (NR)

7 Mandible F 14 Enucleation 2 y (NR)

8 Maxilla F 22 Enucleation 2 y (NR)

9 Mandible F 28 Enucleation 1 y (NR)

10 Ledesma et al. [15] AOT variant Maxilla F 17 Enucleation 11 y (NR)

11 AOT variant Maxilla F 14 Enucleation 8 y (NR)

12 AOT variant Maxilla F 21 Enucleation 5 y (NR)

13 AOT variant Maxilla F 20 Curettage 2 y (NR)

14 AOT variant Mandible M 10 Excision 2 y (NR)

15 AOT variant Maxilla F 21 Enucleation 1 y (NR)

16 AOT variant Mandible F 15 Enucleation 6 m (NR)

17 AOT variant Maxilla M 13 Enucleation 9 y (NR)

18 AOT variant Maxilla F 17 Enucleation 10 m (NR)

19 AOT variant Maxilla F 10 Enucleation 6 m (NR)

20 AOT variant Mandible F 17 Enucleation 1 y (NR)

21 AOT variant Maxilla F 15 Enucleation 2 y (NR)

22 Miyake et al. [12] Hybrid AOT-CEOT Maxilla F 16 Enucleation and curettage 5 y (NR)

P AOT variant Mandible F 17 Enucleation and curettage 7 y (NR)

F Female; M Male; y Year; m Month; NR No recurrence; P present case

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knowledge, the present report shows the longest clinical

follow-up of such variations occurring in the mandible.

Furthermore, there are no former reports on the use of

orthodontic appliances for dental repositioning after enu-

cleation of these tumors, as in the current case.

Variant AOTs that show CEOT-like areas are uncom-

mon odontogenic tumors and their incidence amongst

classic AOTs is unclear. In a multicentric retrospective

study, Leon et al. [18] found 36 AOTs with CEOT-like

areas among 39 classic cases analyzed. A recent investi-

gation demonstrated only four cases of AOTs with CEOT-

like areas among 15 classic cases reviewed [19]. More

evidence-based studies are needed to clarify the real

occurrence of these variations among odontogenic tumors

[18, 19].

It is easy to understand why some authors consider these

lesions as combined epithelial tumors and not variations of a

primary tumor. The literature data are divergent and show

reports of different combinations of odontogenic tumors,

such as AOT with calcifying odontogenic cyst (calcifying

cystic odontogenic tumor) [20], AOT with dentigerous cyst

[21], AOT with odontoma [22], AOT with ameloblastoma

[23], ameloblastoma with odontogenic keratocyst and

ameloblastic fibroma with calcifying odontogenic cyst [24].

Future knowledge on the molecular pathology and cell

culture of odontogenic tumors could shed light on the

development of these lesions. In a recent study, Amm et al.

[25] established diverse primary CEOT epithelial-derived

cell populations and showed the expression of ameloblastin

(AMBN) in these cells. The AMBN gene expresses a pro-

tein that has an important role in the epithelium-mes-

enchyme signaling during odontogenesis. Mutations in this

gene have been identified by capillary electrophoresis in

AOTs and ameloblastomas [26]. Both AOT and CEOT

cells are descended from epithelial odontogenic cell lin-

eages and, if such neoplastic cells receive appropriate

stimuli, they could perhaps give rise to similar ‘‘repro-

grammed’’ neoplastic daughter cells in either lesion or even

any odontogenic tumor of epithelial origin for that matter,

as previously shown in other cells and tissues [27–29].

Such an assumption requires further investigation, as the

inductive potential of the neoplastic epithelial odontogenic

cell lines has not been explored [29].

In conclusion, the clinical data available on these neo-

plasms indicate that these lesions are more likely to be

AOT variants than true hybrid tumors with diverse clinical

behavior (Table 1). Future studies might make it possible

to reach a consensus on nomenclature and classification

criteria, as to whether one ought to classify lesions

according to their biological behavior rather than their

histological variants or to take their histological features as

valid and ignore their biological behavior.

Acknowledgements The authors wish to thank Jeruza Pinheiro da

Silveira Bossonaro and Nadir Severina de Freitas for their excellent

technical expertise and assistance. This research did not receive any

specific Grant from funding agencies in the public, commercial, or

not-for-profit sectors.

Compliance with Ethical Standards

Conflicts of interest There are no conflicts of interest.

Ethical Approval The study has been approved by the institutional

research ethics committee and has been performed in accordance with

the ethical standards as laid down in the 1964 Declaration of Helsinki

and its later amendments.

Informed consent Informed consent was obtained from the partici-

pant included in the study.

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	A Combined Epithelial Odontogenic Tumor? A 7-Year Follow-Up Case
	Abstract
	Introduction
	Case Report
	Discussion
	Acknowledgements
	References