Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27 (2015) 693697

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Journal of Oral and Maxillofacial Surgery,

Medicine, and Pathology
journal homepage: www.elsevier.com/locate/jomsmp

Case Report

Primary intraosseous squamous cell carcinoma arising from

ameloblastoma of the mandible: A case report
Hiroshi Hijioka a , Kazuhide Nishihara b , Hajime Suzuki a , Takayuki Ishida a , Kenichi Kume a ,
Takuya Yoshimura a , Kaori Shima c , Ichiro Semba c , Norifumi Nakamura a,
a
Department of Oral and Maxillofacial Surgery, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima,
Japan
b
Department of Oral and Maxillofacial Functional Rehabilitation, Graduate School of Medicine, University of the Ryukyu, Okinawa, Japan
c
Department of Oral Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

a r t i c l e

i n f o

Article history:
Received 2 September 2014
Received in revised form 26 January 2015
Accepted 20 February 2015
Available online 20 March 2015
Keywords:
Primary intraosseous squamous cell
carcinoma
Odontogenic tumor
Ameloblastoma

a b s t r a c t
Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare odontogenic malignant tumor, and the
origin is considered remnant odontogenic epithelium, odontogenic cyst, and rarely benign odontogenic
tumors. We report an extremely rare case of PIOSCC arising from ameloblastoma.
A 62-year-old man complained a large hard mass at the sublingual to the submental region. The computed tomography images revealed a large multilocular soft tissue mass extending into the bilateral
molar areas with expansion of the mandible and also into the subcutaneous layer at the submental and
the submandibular regions. He had received a curettage treatment of unicystic ameloblastoma in the
right mandible 23 years ago. Malignant odontogenic tumor was suspected, and sectional mandibulectomy following reconstruction using a titanium plate and pedicle latissimus dorsi ap were performed.
Histological examination disclosed a close correlation of intraosseous growth of squamous cell carcinoma and ameloblastoma. PIOSCC arising and dedifferentiated from long term existed ameloblastoma
was mostly considered. There has been no recurrence and no metastasis for more than ve years after
the surgical treatment.
2015 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.

1. Introduction
Primary intraosseous squamous cell carcinoma (PIOSCC) is a
rare odontogenic carcinoma which is considered to be arising from
odontogenic epithelial remnants during odontogenesis, epithelial
lining of odontogenic cysts, and benign odontogenic tumors [13],
although the pathogenesis has been still controversial. PIOSCC arising from ameloblastoma is extremely rare, and there have been
three reported cases [46]. There was only one report showing
coexistence of squamous cell carcinoma (SCC) and ameloblastoma
in the same histological specimen [6].

Asian AOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian
Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese
Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants.
Corresponding author at: Department of Oral and Maxillofacial Surgery, Field
of Oral and Maxillofacial Rehabilitation, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan,
Tel.: +81 99 275 6242; fax: +81 99 275 6248.
E-mail address: nakamura@dent.kagoshima-u.ac.jp (N. Nakamura).

The present case showed intraosseous growth of welldifferentiated SCC in the mandible where ameloblastoma had been
existing consecutively more than 20 years, and the coexisting of
SCC and ameloblastoma with histological close correlation. There
was no histological evidence of malignant transformation of the
ameloblastoma such as secondary ameloblastic carcinoma in the
specimen. The pathogenesis of PIOSCC arising from ameloblastoma
is discussed by comparing with previously reported cases.

2. Case report
A 62-year-old man visited our hospital with a complaint of a
large painless swelling at the lower face. He had medical history
of curettage of ameloblastoma limited in the molar to the premolar region of the right mandible 23 years ago (Fig. 1A), and
the specimen revealed ndings of unicystic ameloblastoma histologically (Fig. 1B). Periodical follow-up was ceased more than
20 years ago after the curettage treatment. He had noticed the
swelling of the anterior alveolar area of the mandible for three
years. There was no symptom of pain and hypoesthesia. A hard

http://dx.doi.org/10.1016/j.ajoms.2015.02.004
2212-5558/ 2015 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.

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H. Hijioka et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27 (2015) 693697

Fig. 1. Panoramic tomography image shows a radiolucent lesion at the right mandible (A), and histological feature of unicystic ameloblastoma showing cystic wall (B; HE,
1.5) and a part of the lining epithelium shows biphasic cuboidal basal cells with nuclear palisading and stellate inner cells with thick hyalinized basement membrane (C;
HE, 10, insert, 20).

mass of 80 mm 70 mm 50 mm was noted at the anterior alveolar to the mental region, and covering alveolar mucosa showed
normal color with tooth indentation (Fig. 2A). There was pus and
keratin debris discharge from skin of the submental region (Fig. 2B).
Panoramic tomography revealed multilocular radiolucent area in
the right mandible and extending into the left side with expansion and destruction of the cortical bone (Fig. 2C). The computed
tomography (CT) images showed the mass with low density as soft
tissue involving the subcutaneous layer at the submental to the
submandibular region (Fig. 2D).
The biopsy specimen from the anterior alveolar region revealed
an epithelial tumor forming follicular nests composed of columnar and cuboidal-shaped basal cells and acanthomatous inner cells
regarded as ameloblastoma. Although there was no cellular atypia
histologically, rapid growth of the tumor after the biopsy suggested a possibility of malignant odontogenic tumor (Fig. 3A and
B). Sectional mandibulectomy between the bilateral mandibular
angles, resection of the submental and the sublingual tissues, and
the bilateral submandibular neck dissection were performed under
the general anesthesia. The mandible and the submental skin were
reconstructed using a titanium plate and the pedicle latissimus
dorsi ap (Fig. 3C and D).
Histologically, the resected specimen revealed invasive growth
of well-differentiated SCC forming nests and sheets with marked
keratinization in the mandibular bone extending into the submucosal and the subcutaneous layers (Fig. 4A and B). There was no
histological evidence suggesting mucosal origin of SCC in the specimen. The carcinoma cells show marked nuclear pleomorphism
with conspicuous nucleoli and atypical mitotic gures (Fig. 4B).

There was follicular proliferation of ameloblastoma closely located

to the SCC nests and fused each other in parts (Fig. 4C and E). The
ameloblastoma nests were composed of columnar basal cells and
inner stellate cells with occasional granular and acanthomatous
changes, and without cellular atypia and mitotic gure (Fig. 4D).
Immunohistochemically, Ki-67 positive cells were in the most of
peripheral portion of the SCC nests, while a few in the ameloblastoma (Fig. 4F). According to the histological ndings, PIOSCC arising
from ameloblastoma was diagnosed, most likely. There was no
metastatic tumor in the neck lymph nodes. Postoperatively, there
has been no complication, recurrence, and metastasis for more than
ve years after the surgery.

3. Discussion
PIOSCC is dened as an intraosseous carcinoma, but it is difcult to distinguish from mucosal SCC in a case of advanced
stage showing destruction of cortical bone and fusion to oral
mucosa [1]. Although the present case is regarded as an advanced
stage of PIOSCC since evidence of destruction of the mandibular cortical bone and the tumor extension into the subcutaneous
layer beyond the mandibular bone, the covering alveolar mucosa
showed normal color and no histological nding suggesting
mucosal origin in spite of marked expansive swelling of the
mass.
PIOSCC is subcategorized into three groups according to the
origin; (1) solid type, considered to be derived from odontogenic
epithelial remnants such as the periradicular epithelial rests of

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695

Fig. 2. Preoperative state shows expanded alveolar area (A) and marked swelling of lower face (B). Panoramic tomography (C) and CT (D) images disclose a mass expanding
between bilateral molars and the subcutaneous region.

Malassez and reduced enamel epithelium, and rarely, appeared

as dedifferentiation from ameloblastoma; (2) derived from keratocystic odontogenic tumor; and (3) derived from odontogenic cysts
[1].
In the present case, the coexistence of well-differentiated SCC
and follicular proliferation of ameloblastoma close to and fusion
to each other was histologically evident. According to the medical
history and clinical symptoms, secondary ameloblastic carcinoma
was highly suspected before the operation clinically, however, the
resected tumor showed no histological features of ameloblastic

carcinoma such as atypical ameloblastic cell with nuclear pleomorphism and increase of mitotic gures [1,7]. Although ameloblastic
carcinoma has a possibility of partial squamous differentiation
[1], the present case revealed the carcinoma showing extensive
squamous cell differentiation. Furthermore, there was no follicular and/or cord like nests but forming large nests and sheets with
gradual squamous cell differentiation of basal to keratinized cell.
Immunostaining of Ki-67 showed the evidence of conspicuous difference between in the SCC and in the ameloblastoma. Therefore,
it is considered that the remnant of ameloblastoma for long term

Fig. 3. Rapid growth of the tumor with prominence of keratinizing mass (A and B). Postoperative view of the face constructed with a titanium plate and the pedicle latissimus
dorsi ap (C and D).

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H. Hijioka et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27 (2015) 693697

Fig. 4. Histological ndings of the resected tumor showing well-differentiated SCC forming nests and sheets with marked keratinization (A; HE, 4). The SCC cells show marked
nuclear pleomorphism and large prickle cells (B; HE, 23). There is coexistence of SCC and ameloblastoma (C; HE, 15). The follicular proliferation of the ameloblastoma
shows no cellular atypia (D; HE, 20). The ameloblastoma is connecting to the SCC in a part (E; HE, 10). Ki-67 positive cells are present mostly in the SCC nests at the left
area, while a few positive cells in the ameloblastoma are present at the right area in same area of Fig. 2C (F; Ki-67, 15).

in the mandible might have been dedifferentiated and developed

to SCC.
There have been only three reported cases suggested as PIOSCC
arising from ameloblastoma [46]. Gonzales-Garcia et al. discussed
two PIOSCCs in the maxilla and the mandible were considered to
be arising from ameloblastoma, or de novo, however, no histological feature of ameloblastoma was demonstrated in their report [4].
Ueta et al. reported a case of PIOSCC occurred at the surgical margin
of re-recurrent ameloblastoma at the mandibular ramus. However,
the ameloblastoma and the SCC were observed metachronically,
and there was no clear histological evidence of coexistence of the
two different lesions [5]. Only one case reported by Hamakawa
et al. demonstrated the coexistence of SCC and ameloblastoma
histologically. Because sequential occurrence of both lesions was

obscure, they did not conclude that the SCC has been arising from
the ameloblastoma, but concluded the both tumors had occurred
synchronously [6]. The present case has a histological evidence of
the pre-existing ameloblastoma at the same location where SCC
had developed successively. Therefore it could be considered that
PIOSCC arising and dedifferentiated from the long term existed
ameloblastoma as a pathogenesis.
The prognosis of PIOSCC is still uncertain in general, since a large
number of cumulative analyses are difcult for their rare occurrence. There was no signicant difference of 5-year survival rate
between the 113 cases of PIOSCC arising from odontogenic cysts
and the 87 cases of de novo PIOSCC as 38.0% and 36.337.8%, respectively [3]. It was reviewed the 36 cases in the literature, and noticed
recurrence had occurred in 56% (19/34) cases [8], although the

H. Hijioka et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 27 (2015) 693697

cases meet the previous WHO classication (1992). As it was suggested the radical treatment of PIOSCC for better prognosis [3,8], we
performed the radical surgical treatment as sectional mandibulectomy for complete resection of the lesion, and the patient has
been revealed favorable prognosis, no recurrence and metastasis
for more than ve years.
This case report should provide novel information of the pathogenesis and the management of PIOSCC.
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