Vol. 114 No.

5 November 2012

Solid-type primary intraosseous squamous cell carcinoma of the

mandible: a case report with histopathological and imaging
features
Hidenobu Matsuzaki, DDS,a Naoki Katase, DDS, PhD,b Tatsushi Matsumura, DDS, PhD,c Marina Hara, DDS,d
Yoshinobu Yanagi, DDS, PhD,e Hitoshi Nagatsuka, DDS, PhD,f Seiji Iida, DDS, PhD,g and
Jun-Ichi Asaumi, DDS, DMSci,h Okayama, Japan
OKAYAMA UNIVERSITY GRADUATE SCHOOL OF MEDICINE, DENTISTRY, AND PHARMACEUTICAL SCIENCES

Primary intraosseous squamous cell carcinoma (PIOSCC) is a rare malignant odontogenic tumor arising from
odontogenic epithelial remnants within the jawbones. PIOSCC is histopathologically divided into 3 types: solid-type
carcinoma, carcinoma derived from a keratocystic odontogenic tumor, and carcinoma derived from an odontogenic cyst. In
this article, we report a case of solid-type PIOSCC involving reactive bone formation in the mandible in a 60-year-old female
patient together with its histopathological and imaging findings. (Oral Surg Oral Med Oral Pathol Oral Radiol 2012;114:
e71-e77)

Primary intraosseous squamous cell carcinoma (PIOSCC)

is a rare central jawbone carcinoma arising from odontogenic epithelial remnants. In 2005, the World Health Organization (WHO)1 divided PIOSCC into 3 types: solidtype carcinoma, carcinoma arising from a keratocystic
odontogenic tumor, and carcinoma arising from an odontogenic cyst. The definitive diagnosis of PIOSCC is often
difficult, and the diagnostic criteria for PIOSCC remain
obscure. Some authors have reported that one of the
histopathological definitions of PIOSCC is a squamous
cell carcinoma (SCC) arising within the jawbone and does
not involve the oral mucosa.1-3
The radiographic features of PIOSCC display great
variation both within and between each type.1-28 Solidtype PIOSCC commonly displays an osteolytic appearance with ill-defined irregular margins, whereas the
other types are often indistinguishable from benign
jawbone lesions with well-defined margins during their
early development.1 Larger PIOSCC of all types have
various destructive effects on the jawbone.1 Many aua

Assistant Professor, Department of Oral Diagnosis and Dentomaxillofacial Radiology.

b
Assistant Professor, Department of Oral Pathology and Medicine.
c
Assistant Professor, Department of Oral and Maxillofacial Reconstructive Surgery.
d
Research Fellow, Department of Oral and Maxillofacial Radiology.
e
Senior Assistant Professor, Department of Oral Diagnosis and Dentomaxillofacial Radiology.
f
Professor, Department of Oral Pathology and Medicine.
g
Professor, Department of Oral and Maxillofacial Reconstructive
Surgery.
h
Professor, Department of Oral and Maxillofacial Radiology.
Received for publication Feb 15 2012; returned for revision May 1,
2012; accepted for publication May 9, 2012.
2012 Elsevier Inc. All rights reserved.
2212-4403/$ - see front matter
http://dx.doi.org/10.1016/j.oooo.2012.05.019

thors have reported conventional radiographic and

computed tomography (CT) findings of PIOSCC, although to the best of our knowledge, there is no report
about magnetic resonance imaging (MRI) findings and
18
F-fluorodeoxyglucosepositron emission tomography
(FDG-PET) findings of PIOSSC.1,2,4,6-10,12,13,15-27 Several authors have reported rare radiological findings of
PIOSCC, including small radiopaque foci and osseous
metaplasia.11,16,23,25,29,30 In this case report, we describe a solid-type PIOSCC that displayed reactive
bone formation in the mandible, as well as its histopathological features and imaging characteristics.

CASE REPORTS
In June 2007, a 60-year-old woman was referred to a
general dental practitioner. The woman complained that she
had a tingling sensation in the lower left gingiva of her molar
region and continuous discomfort deep in her right ear. After
detecting a bone defect in the inferior molar region of her left
mandibular body on panoramic radiographs, her primary doc-

Statement of Clinical Relevance

Primary intraosseous squamous cell carcinoma
(PIOSCC) is a rare malignant odontogenic tumor
arising from odontogenic epithelial remnants
within the jawbones. PIOSCC are histopathologically divided into 3 types: solid-type carcinoma,
carcinoma derived from a keratocystic odontogenic tumor, and carcinoma derived from an
odontogenic cyst. In this article, we report a case
of solid-type PIOSCC involving reactive bone
formation in the mandible in a 60-year-old female
patient together with its histopathological findings and imaging findings.

e71

ORAL AND MAXILLOFACIAL RADIOLOGY

e72 Matsuzaki et al.

Fig. 1. Panoramic radiograph showing a radiolucent area

with ill-defined margins in the right mandibular body.
tor recommended that she undergo further evaluation and
referred her to our hospital in July 2007. She did not have a
relevant medical history.
No abnormal findings were detected in the lower right
molar region in an intraoral examination. A panoramic radiograph displayed a radiolucent area with ill-defined margins in
the right mandibular body, with the area extending from the
lower right molars to the retromolar triangle (Figure 1). With
bone-window axial and reconstructed coronal CT images,
extensive destruction of the lingual bone cortex was detected,
and hyperdense areas that displayed irregular shapes and a
reactive bone formationlike appearance were detected within
the area affected by bone absorption (Figure 2, a and b). On a
soft-tissue-window axial CT image (Figure 2, c), the area of
bone resorption was filled with soft tissues displaying strong
enhancement after iohexol intravenous injection (Figure 2, d),
and a right submandibular lymph node was enlarged (11.5
7.8 mm) and showed strong enhancement.
With a 1.5-T unit with a headneck coil (Magnetom Vision;
Siemens, Erlangen, Germany), we used gadodiamide and performed contrast-enhanced (CE) MRI, including dynamic studies. The resultant MR images showed a heterogeneous mass
within the mandible, with the mass displaying hypo- to isointensity on T1-weighted images (WI), iso- to hyperintensity on
short TI inversion recovery (STIR) images, and strong enhancement on CE-T1WI (Fig. 3, a c). An enlarged right submandibular lymph node displayed hyperintensity on STIR images and
strong enhancement on CE-T1WI. We performed dynamic contrast-enhanced (DCE) MRI with 3-dimensional fast imaging.
The DCE-MRI series was composed of 14 consecutive scans
performed at 1-second intervals (acquisition time for each scan:
14 s). The total scan time for this series was 210 seconds. A
second and third series of DCE-MRI were acquired at approximately 450 and 650 seconds after the administration of contrast
medium, respectively. A time signal intensity curve (TIC) was
created from the dynamic images; that is, regions of interest
(Figure 3, d) were drawn on a computer monitor, and the mean
signal intensity values of the regions of interest were calculated
using a workstation (Synapse Vincent, Fujifilm Medical Co.,
Tokyo, Japan). These values were plotted against time to create

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November 2012
a TIC. The TIC of our PIOSCC peaked at 100 seconds and then
gradually decreased with slight washout of the contrast medium
(Figure 3, e).
On FDG-PET imaging, elevated FDG uptake was detected
in the right mandible (maximum standardized uptake value
[SUVmax]: 18.4; Figure 4, a). No abnormal FDG uptake that
was suggestive of another primary tumor or distant metastasis
was detected on the FDG-PET images (Figure 4, b).
From these imaging findings, we diagnosed the lesion as a
primary malignant tumor arising from the right mandible with
right submandibular lymph node metastasis. Thus, an incisional biopsy was performed. As a result, the lesion was
suspected to be a PIOSSC. The patient underwent segmental
resection of right mandible and right radical neck dissection
under general anesthesia, and the diagnosis was histopathologically confirmed after the surgery.
During a gross examination of the surgical specimen, the
surface of the lesion was found to be covered with healthy
oral mucosa tissue (Figure 5). The specimen was fixed and
routinely processed for pathologic diagnosis. Histologically,
the solid tumor had invaded the bone marrow (Figure 6, a).
The tumor cells varied in size, displayed cellular atypia, and
formed nests of keratinized tissue in the desmoplastic fibrous
stroma (Figure 6, b). The tumor displayed a strong bony
invasive phenotype (i.e., it had completely replaced the mandibular bone and extended into the muscles). Destruction of
the inferior alveolar canal was also observed. In some areas,
woven bone formation was observed, suggesting reactive
bone formation (Figure 6, c and d).
The lesions histologic findings included the characteristic
features of SCC, but no dysplasia or SCC was observed in the
covering epithelium, suggesting that the tumor arose from the
central jaw (Figure 6, e). Mucin staining revealed that no
mucous cells were observed, which ruled out the diagnosis of
central mucoepidermoid carcinoma. Taking these histologic,
radiological, and clinical findings into account, the lesion was
diagnosed as a PIOSCC.
The patient developed left submandibular and superior internal jugular lymph node metastasis 11 months after treatment and
was salvaged with radical neck dissection. At 4 years after the
second surgery, there was no sign of recurrence.

DISCUSSION
PIOSCC is a rare malignant odontogenic tumor that
accounts for approximately 1% to 2.5% of all odontogenic tumors.31-33 PIOSCC displays a predilection for
males (2:1 male/female ratio).1-3,5,9,13,14,23-25,34,35 Although it can occur in all age groups, it most commonly
occurs in the fifth decade.1-3,5,9,13,14,23-25,34,35 PIOSCC
is more often found in the body and posterior mandible
than in the maxilla.1-3,5,9,13,14,23,25,34,35 Clinically,
PIOSCC is associated with various symptoms depending on its location, size, and type; these symptoms
include pain, swelling, sensory disturbance, and routine
dental disorders.1-3,9,13,14,18,23,25,26,35 The patient who
is the subject of this case report experienced a tingling
sensation in the lower left gingiva of her molar region
without paresthesia of the lower lip.

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Matsuzaki et al. e73

Fig. 2. Computed tomography images. (a, b) Axial and reconstructed coronal bone-window images showing widespread bone
destruction in the right mandible with areas displaying a reactive bone formationlike appearance and extensive destruction of the
lingual cortical bone. On an axial, soft-tissue-window image (c), the areas of bone resorption had been filled with soft tissue, and
heterogeneous strong enhancement was detected on contrast-enhanced images (d).

PIOSCC, which develops from remnants of the

odontogenic epithelium, is defined as an SCC arising
within the jawbones. In 1972, the WHO36 suggested the
term primary intraosseous odontogenic carcinoma
(PIOC). Subsequently, the WHO classification was
modified by adding ameloblastic carcinoma.5 The classification was further modified in 1984,37 and in 1989,
intraosseous mucoepidermoid carcinoma was added to
the classification of PIOC.9 In 2005, the WHO1 used
the term PIOSCC and categorized it into 3 types: solidtype carcinoma, carcinoma arising from a keratocystic
odontogenic tumor, and carcinoma arising from an
odontogenic cyst. The detailed subcategories of
PIOSCC are as follows: (1) solid tumors that invade
marrow spaces and induce osseous resorption, (2) SCC
arising from the lining of an odontogenic cyst, and (3)
an SCC associated with other benign epithelial odontogenic tumors.1,38 In the present case, a histopathological examination revealed that a tumor mass was growing in the bone, and no finding was indicative of direct
invasion of the SCC from the covering squamous epi-

thelium. The tumor cells displayed the characteristic features

of squamous cell carcinoma. No preceding odontogenic cyst
or tumor or any other primary squamous cell carcinoma was
indicated. PIOSCC usually presents as an extensive osteolytic lesion; however, woven bone formation was observed in
the present case. To our knowledge, bone formation in
PIOSCC is a rare finding. Osseous metaplasia resulting from
stromal metaplasia in PIOSCC has been reported in a few
articles11,16,23,25,30; however, the histopathological features of
the bone formation in the present case were suggestive of
reactive bone formation. Reactive bone formation is generally observed in bone metastasis and therefore can complicate the exclusion of metastatic SCC.
Radiologically, many authors have reported conventional radiographic and CT findings of PIOSCC, which
displays great variations.2,4,6-13,15-28 In these articles,
PIOSCC arising from odontogenic cysts and tumors
produced radiographic features similar to that of benign
jawbone lesions (i.e., a cyst-like appearance with or
without surrounding bone destruction). On the other
hand, solid-type PIOSCC commonly presents as an

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e74 Matsuzaki et al.

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November 2012

Fig. 3. Magnetic resonance images taken in the axial plane and a time signal intensity curve. A mass is present in the right
mandible and displays heterogeneous hypo- to isointensity on T1-weighted images (a) and heterogeneous iso- to hyperintensity
on short TI inversion recovery images (b). On contrast-enhanced T1-weighted images, the mass displayed strong heterogeneous
enhancement (c). The region of interest (red line) is indicated on a dynamic image (d). The time signal intensity curve increased
for 100 seconds and then gradually decreased until about 700 seconds (e).

osteolytic radiolucent lesion, and our case followed this

pattern. The CT findings of our PIOSCC revealed the
presence of reactive bone formation with a groundglass appearance, which is commonly observed in fibrous dysplasia. Several authors have reported PIOSCC
that displayed small radiopaque foci, which were found
to be calcifications or dentinoid structures in histopathological examinations, and osseous metaplasia, although the CT features of our PIOSCC differed from
those of the previously reported lesions.11,16,23,25,29,30

To the best of our knowledge, there is no report

about the MRI features of PIOSCC. In our case, MR
images depicted an intraosseous mass that displayed
heterogeneous hypo- to isointensity on T1WI and heterogeneous iso- to hyperintensity on STIR images. Regarding the MRI findings of our PIOSCC, a possible
reason for its lack of homogeneity was the presence of
reactive bone formation. Therefore, we considered that the
magnetic resonance images of our case might show atypical features compared with those of common solid-type

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Matsuzaki et al. e75

Fig. 4. (a) Axial 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/CT image showing FDG accumulation in the
lesion in the right mandible (SUVmax 18.4). (b) No abnormal FDG accumulation was detected on FDG-PET images.

Fig. 5. A gross examination of the surgical specimen revealed

that the lesion was covered with healthy oral mucosa tissue.

PIOSCC. On the other hand, the magnetic resonance

features of our case corresponded with its histopathological features. On CE-T1WI, the tumor mass showed
strong enhancement, and the TIC of our PIOSCC
peaked at 100 seconds and then gradually declined
during washout of the contrast medium. Among head
and neck lesions, the TIC of malignant neoplasms
commonly show rapid increases, and we have previously reported that the TIC of oral SCC peaked at
approximately 80 seconds.39 The peak enhancement
time of our PIOSCC was, however, longer than the
typical value for oral SCC but similar to that of ameloblastoma, which is the most common form of benign
odontogenic tumor.31-33,40 We considered 2 possibilities why the peak enhancement time of our PIOSCC
was delayed compared with the previously reported
values for SCC. PIOSCC arises within the jawbones,
whereas oral SCC commonly arises from the soft tis-

sues of the oral mucosa; hence, the blood flow from the
surrounding tissues might differ between the 2 lesions.
In addition, the presence of reactive bone formation and
fibrous tissue in the center of the lesion might have
affected the flow of contrast medium into the tumor
mass. Previous reports have stated that in some tumors
the presence of rich fibrous tissue in the extracellular
spaces caused reduced contrast medium washout.41,42
The TIC of our case gradually decreased after its peak
(i.e., contrast medium washout was delayed compared
with that observed for other SCC).39 The histopathological findings of our PIOSCC, which displayed bone
formation and fibrous tissue in its central region, corresponded with the results of previous studies.
Generally, FDG-PET is a useful modality for evaluating malignant tumors as well as the primary site, lymph
nodes, and distant metastasis. In our case, strong FDG
uptake (SUVmax 18.4), which indicated that the tumor was
malignant, was detected in the mandible, whereas no other
abnormally high uptake (suggestive of another primary
tumor or distant metastasis) was observed. As a diagnostic
criteria for PIOC, several authors have proposed the exclusion of other primary tumors on chest radiographs
obtained at the time of diagnosis.2,3 Therefore, considering the above criterion, FDG-PET of PIOSCC is useful
for evaluating the primary site and excluding the presence
of another primary tumor. In addition, the present case
met both the radiological and the histopathological criteria
for the diagnosis of PIOSCC.

CONCLUSIONS
We report a rare case of solid-type PIOSCC in the
mandible that displayed areas of reactive bone formation. CT images and MRI (including dynamic studies of
our PIOSCC) detected atypical features, although they
were reflective of its histopathological features. FDG-

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e76 Matsuzaki et al.

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November 2012

Fig. 6. Histopathological findings. (a) Full-sized image of a representative histologic section. (b) The tumor cells formed nests
of keratinized tissue and displayed the characteristic features of squamous cell carcinoma (200). (c) Tumor cells had invaded
into the inferior mandibular nerve (*). Reactive bone formation was observed (2). (d) Reactive bone showed an immature woven
bone-like appearance (200). (e) The surface of the lesion was covered with epithelial tissue without dysplasia (2).

PET/CT is useful for diagnosing PIOSCC because of its

ability to detect the presence of other primary tumors.
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Reprint requests:
Jun-ichi Asaumi
Department of Oral and Maxillofacial Radiology
Field of Tumor Biology
Okayama University Graduate School of Medicine, Dentistry, and
Pharmaceutical Sciences
5-1, Shikata-cho, 2-Chome
Okayama-city
Okayama 700-8558
Japan
asaumi@md.okayama-u.ac.jp