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Taiwan J Oral Maxillofac Surg 台灣口外誌
Introduction
Ameloblastoma is a common odontogenic
tumor in the jaw. It can be divided into
subgroups according to di f ferent cl inical
features or microscopic patterns. Although
most o f ameloblastomas exhib i t speci f ic
odontogenic features by hematoxylin and
eosin (H&E) histopathological examination,
there are cases that have been misdiagnosed
in the first set of biopsy.1-3 Simultaneous or
chronological occurrence of malignant neoplasm
Synchronous Oral Squamous Cell Carcinoma and Ameloblastoma in a Patient and Using CK8
Expression as An Aid to Differential Diagnosis — Case Analysis
Ya-Wei Chen*, Wing-Ying Li** and Shou-Yen Kao*
* Oral & Maxillofacial Surgery, Department of Stomatology, Taipei Veterans General Hospital,
Taipei, Taiwan, R.O.C.
** Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
Abstract
We report a case of double oral tumor in two nearby location of the oral cavity. The patient was transferred from a local hospital where the diagnosis of squamous cell carcinoma of both lesions was made. The patient was received the operation in our hospital and surprisingly, the final pathological diagnosis disclosed simultaneous occurrence of oral squamous cell carcinoma (OSCC) and acanthomatous ameloblastoma. We found this case was easily misinterpreted diagnosed if the pathologist is not expert at oral pathology and the pathological examination was made merely by plain H&E stain. To clearly define different histological characteristics between the two lesions, immunohistochemistry (IHC) was applied. It showed different expression of cytokeratin 8 (CK8) in the two lesions. Further CK8 staining in other 20 cases of ameloblastomas and 15 cases of OSCC affirm the finding that ameloblastomas were strong to moderately immunoreactive to CK8 while OSCC were not. Our finding suggests that CK8 may be helpful in distinguishing ambiguous ameloblastomas from OSCC.
Key words: ameloblastoma, cytokeratin 8, oral squamous cell carcinoma.
Taiwan J Oral Maxillofac Surg19: 170-178, September 2008 台灣口外誌
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台灣口外誌 Using CK8 Expression as An Aid to Differential Diagnosis ─ Case Analysis
and ameloblastoma in the oral cavity is rare,
but this has been reported.1-6 The following
case report descr ibed the s imul taneous
occurrence of a squamous cell carcinoma (SCC)
and an acanthomatous ameloblastoma in two
nearby regions—the tongue and the gingiva.
Immunohistochemistry (IHC) was employed by
our pathologists in order to clearly identify the
different characteristics of the two lesions. It was
found that cytokeratin 8 (CK8) immunoreactivity
were totally different in these two lesions. Further
CK8 immunostaining was performed in the other
20 cases of ameloblastomas and 15 cases of
OSCC and the result confirmed this finding. The
case drew our attention because it was at first
misdiagnosed pathologically as SCC at another
hospital, and such misdiagnosis could lead to
inappropriate therapies. In such circumstances,
we showed that CK8 IHC is helpful for differential
diagnosis between the ameloblastomas and the
squamous cell carcinomas.
Case Report
A 43-year-old male presented to our
hospital with the chief complaint of pain and
chronic wound over the right side border of the
tongue and also a progressively growing mass
over the right lower gingiva. The problem began
2 months prior to the admission. He has visited
another hospital 1 week before and biopsy was
done there. The pathological diagnosis was SCC
in the tongue and the gingiva. He was then
referred to our hospital for therapeutic treatment.
The patient was a healthy-looking man whose
medical history and general physical examination
were unremarkable. Oral examination disclosed a
2 × 1 cm ulcerative tumor on the right side border
of tongue and a 1 × 1 cm papillomatous lesion
with a bulging buccal plate over the right lower
gingiva. Computed tomography (CT) revealed a 3
× 2 cm ill-defined, heterogeneous mass with bony
destruction over the right side parasymphysis
region of mandible. The lesion over the tongue
was not depicted clearly on CT images; neither
was significant neck lymphadenopathy (Figure 1).
Under general anesthesia, resection of the
tongue lesion and the papillomatous lesion at
lower gingival was performed. The specimens
were sent to our pathologist for diagnosis. At the
microscopic level, the tumor of the tongue showed
a picture of moderately differentiated SCC.
The tumor of the lower gingiva was dominated
by acanthomatous type of ameloblastoma and
exhibited cystic degeneration in the squamous
components (Figure 2). The pattern might confuse
acanthomatous ameloblastoma with SCC if the
pathologist is not familiar with the oral pathology.
Further special stains were performed to study
the histological features of the two lesions.
We found different expression of CK8 between
OSCC and acanthomatous ameloblastoma by
immunohistochemistry. The ameloblastoma had
strong to moderate CK8 immunoreactivity and
the OSCC are negative for CK8 (Figure 3).
Two weeks later, a marginal mandibulectomy
was performed under the diagnosis of ameloblas-
toma in the right lower gingiva. After the surgery,
the patient kept regular outpatient follow-up in
our hospital and no tumor recurrence was found
in 5 years.
Material & Method
Surgical specimens were collected from
21 ameloblastomas and 16 oral squamous cell
carcinomas (OSCC) including the present case.
All tissue specimens were harvested from the
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Taiwan J Oral Maxillofac Surg 台灣口外誌
Fig. 1. Head and neck computed tomography scan of the patient. A heterogeneous soft-tissue mass
about 3 × 2 cm over the right side paramedian mandible with bone destruction was noted.
Fig. 2. Section of the two tumors with hematoxylin
and eosin staining in the patient (a)
squamous cell carcinoma of the tongue
(or ig ina l magn i f i ca t ion x 200) ; (b )
ameloblastoma of the gingiva and mandible
(original magnification x 100); and (c)
acanthomatous region of the ameloblastoma
(original magnification x 200).
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台灣口外誌 Using CK8 Expression as An Aid to Differential Diagnosis ─ Case Analysis
patients treated in Taipei-Veterans General
Hospital between year 2001 and 2006. The
clinicopathological features including age, gender,
site, and subtypes of ameloblastomas were
recorded (Table 1).
All samples were fixed by formalin and
embedded in paraffin. They were sectioned
into 3 μm in width and mounted on slides
(Muto-glass, silane coating micro slides). The
immunohistochemical detection of cytokeratin
8 (CK8) was carried out using immunodetection
kit manufactured by Becton Dickinson. All the
sectioned slides were incubated for 60 min in a
heat bath at 60 Celsius degree, deparaffinized
in xylene and re-hydrated by immersion in a
graded series of ethanol dilutions. They were
immersed in 10 mM sodium citrate solution,
in a microwave oven, to retrieve antigenicity.
Sections were quenched with 3% fresh H2O2 for
10 min to inhibit endogenous tissue peroxidase
activity, and rinsed with 1x phosphate-buffered
saline (PBS) for 5 min twice. They were further
incubated in blocking serum for 30 min and then
for 33 minutes with prediluted anti-cytokeratin
8 (CAM5.2) in a humid chamber. After washing
with 1x PBS for 5 min twice, sections were then
incubated with biotinylated secondary antibody
solution for 30 min. LAB-SA_streptavidin-
Avidin-Biotin detection reagent (Zymed, South
San Francisco, CA, USA) was subsequently
added evenly over the sections and incubated for
30 min. The sections were washed with 1x PBS
for 5 min twice, incubated with freshly prepared
3,3’-Diaminobenzidine tetrahydrochloride
(Zymed, South San Francisco, CA, USA)
substrate solution for 15 min and then washed
with 1x PBS. All IHC staining was performed
at room temperature. The sections were finally
counterstained with hematoxylin, washed with 1x
PBS and deionized distilled water, dehydrated,
washed, and then mounted. An identical section
without the addition of the primary antibody
was processed in the same manner as a negative
control. The extent of immunoreactivity was
Fig. 3. Representative pictures of the results of immunohistochemical staining with CK8 in the patient
(a) squmaous cell carcinoma over the tongue shows grossly negative CK8 immunoreactivity; and
(b) the epithelial components of the ameloblastoma shows strong CK8 immunoreactivity. (original
magnification x 400).
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Taiwan J Oral Maxillofac Surg 台灣口外誌
Table 1. Clinicopathological features including age, gender, site, the pathology and the IHC
results in the 20 ameloblastomas and the 15 oral squamous cell carcinomas treated in
Taipei-Veterans General Hospital between year 2001 and 2006.
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台灣口外誌 Using CK8 Expression as An Aid to Differential Diagnosis ─ Case Analysis
scored based on the percentage of positively
stained tumor cells found in each tissue section.
Cell content >75% was considered strong positive
(+++), 30-75% was considered moderate positive
(++), 10-29% was considered weak positive (+),
0-9% was considered negative (-).
Results
Excluding the current case, there was totally
twenty patients with primary ameloblastoma
examined, with age ranging from 12 to 78 years.
The ratio of males and females was 15 to 5. Four
of the tumors were in maxilla and 16 in mandible.
The histological subtypes of ameloblastomas
included plexiform pattern (n = 8), acanthomatous
pattern (n = 6), follicular pattern (n = 5), and
mixed plexiform and follicular pattern (n = 1). All
the specimens of ameloblastomas had strong to
moderate CK8 immunoreactivity and the 15 cases
of OSCC are negative for CK8 immunostaining
(Table 1 and Fig 3).
Discussion
Odontogenic tumors are neoplasms of jaws
derived from epithelial and / or ectomesenchymal
elements of the tooth-forming apparatus.
Ameloblastomas are one of the most prevalent
odontogenic tumors with the incidence ratio of
22.7~69.8%.7-9 They are tumors of odontogenic
epithelium with multiple microscopic subtypes,
such as follicular, plexiform, acanthomatous,
granular cell, and basal cell pattern. Although
these odontogenic tumors have particular
histological characteristics, it is not uncommon
for them to be misdiagnosed by pathologists
who are not familiar with oral pathology. For
ameloblastomas that do not show the obvious
characteristic features of dental epithelium
or when they are predominated by squamous
component with invasive growth pattern,
the diagnosis is sometimes dif f icult. This
is particularly eminent for acanthomatous
ameloblastoma since squamous metaplasia may be
present.10
In this article, we present a case of simul-
taneous occurrence of OSCC and acanthomatous
ameloblastoma which was at first diagnosed as
SCC both in other hospital. For the proximity of
the two lesions and the provisional diagnosis, it
would be possible that someone who took over
the case would follow the misinterpreted diagnosis
and perform a commando surgery for the patient.
Actually, the clinical appearance of the
papillomatous lesion on the right lower buccal
gingival was quite different from the ulcerative
tumor over the right tongue border. The lesion
on the tongue was small and could not be
depicted clearly on CT image. The lesion on the
right side mandible was larger and present with
bone destruction. To be cautious, we performed a
tumor resection on the tongue lesion and biopsy
on the papillary tumor of right mandible. The
histopathological diagnosis were finally confirmed
by a series of special stains that the two tumors
were totally different. Based on the diagnosis,
a definite treatment for the ameloblastoma was
performed by marginal mandibulectomy. No
further neck dissection was administered because
the SCC over the tongue was only on stage T1.
The result showed that immunohistochemical
(IHC) staining may be useful in differential
diagnosis of odontogenic tumors and SCC
by cytokeratin expression. The subsets of
cytokeratins which an epithelial cell expresses
are related to the type of epithelium, the moment
in the process of terminal differentiation and
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Taiwan J Oral Maxillofac Surg 台灣口外誌
the stage of development. Immunohistochemical
expression of cytokeratins in odontogenic
epithelium or neoplasms has been studied
before. Cytokeratin (CK)14, a basal cell type of
cytokeratin, was expressed in all cells of dental
germs and reduced epithelium of the enamel
organ but not in preameloblasts and secreting
ameloblasts. Cytokeratin7 was expressed in the
cells of the Hertwig root sheath and the stellate
reticulum. It was also found that cytokeratin13
was expressed in the dental lamina and stellate-
like structure in the ameloblastoma.11 Fukumashi
et al12 reported that different kinds of cytokeratin
have positive immunoreactions in different
histological patterns of ameloblastomas. But only
cytokeratin8 (CK8) reacted constantly to the
constituting cells in all types of ameloblastomas.
CK8 belongs to type B subfamily of high-
molecular-weight keratins and is primarily
found in non-squamous epithelium or secretory
epithelium of human tissue. The CK8 antibody
(CAM5.2) stains most ectodermal-derived tissue,
including liver and renal tubular epithelium. Thus
it can be used for diagnosis of hepatocellular
carcinoma and renal cell carcinomas. In this
case, CK8 IHC can differentiate the SCC at the
tongue from ameloblastoma at the gingiva in the
same patient. The same protocols were used
to study the other 20 ameloblastomas and 15
OSCC, and the results showed consistency that
ameloblastomas were immunoreactivity to CK8
while OSCC were not.
Conclusion
This report presented a case of two
synchronous tumor with different diagnosis. It is
therefore important to carefully diagnose each
of the tumors in such circumstances. Using CK8
IHC we can differentiate ambiguous amelobla-
stoma from OSCC.
References
1. Nishimura T, Nagakura R, Ikeda A, Kita
S. Simultaneous occurrence of a squamous
cell carcinoma and an ameloblastoma in the
maxilla. J Oral Maxillofac Surg 58: 1297-
1300, 2000.
2. Tucker MR, Dechamplain RW, Jarrett JH.
Simultaneous occurrence of an ameloblastoma
and a squamous cell carcinoma of the
mandible. J Oral Maxillofac Surg 42: 127-
130, 1984.
3. Nakamura N, Higuch i Y, Tash i ro H,
Shiratsuchi Y. Mandibular ameloblastoma
associated with salivary gland tumor. Int J
Oral Maxillofac Surg 17: 103-105, 1988.
4. Ueta E, Yoneda K, Ohno A, Osaki T.
Intraosseous carcinoma arising from mandi-
bular ameloblastoma with progressive
invasion and pulmonary metastasis. Int J Oral
Maxillofac Surg 25: 370-372, 1996.
5. Ide F, Shimoyama T, Horie N, Shimizu S.
Intraosseous squamous cell carcinoma arising
in association with a squamous odontogenic
tumour of the mandible. Oral Oncol 35: 431-
434, 1999.
6. Baden E, Doyle JL, Petriella V. Malignant
transformation of peripheral ameloblastoma.
Oral Surg Oral Med Oral Pathol 75: 214-219.
1993.
7. Jing W, Xuan M, Lin Y, Wu L, Liu L, Zheng
X, Tang W, Qiao J, Tian W. Odontogenic
tumours: a retrospective study of 1642 cases
in a Chinese population. Int J Oral Maxillofac
Surg 36: 20-25. 2007.
8. Ledesma-Montes C, Mosqueda-Taylor A,
- 177 -
台灣口外誌 Using CK8 Expression as An Aid to Differential Diagnosis ─ Case Analysis
Carlos-Bregni R, de Leon ER, Palma-Guzman
JM, Paez-Valencia C, Meneses-Garcia A.
Ameloblastomas: a regional Latin-American
multicentric study. Oral Dis 13: 303-307,
2007.
9. Okada H, Yamamoto H, Tilakaratne WM.
Odontogenic tumors in Sri Lanka: analysis of
226 cases. J Oral Maxillofac Surg 65: 875-
882, 2007.
10. Velez I, Siegel MA. Head and neck diagnostic
challenge. N Y State Dent J 70: 22-23, 2004.
11. Crivelini MM, de Araujo VC, de Sousa SO,
de Araujo NS. Cytokeratins in epithelia of
odontogenic neoplasms. Oral Dis 9: 1-6,
2003.
12. Fukumash i K , Enok i y a Y , I noue T .
Cytokeratins expression of constituting cells
in ameloblastoma. Bull Tokyo Dent Coll 43:
13-21, 2002.
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Taiwan J Oral Maxillofac Surg 台灣口外誌
Received: May 5, 2008Accepted: June 28, 2008Reprint requests to: Dr. Ya-Wei Chen, Dr. Shou-Yen Kao, Chair, Oral & Maxillofacial Surgery,
Department of Dentistry, Taipei Veterans General Hospital, No 201, Sec 2, Shih-Pai
Road, Taipei, Taiwan 11217.
利用CK8免疫螢光染色鑑別診斷同時發生的
造釉細胞瘤及口腔鱗狀細胞癌–病例分析
陳雅薇* 李永賢** 高壽延*
* 台北榮民總醫院口腔醫學部口腔顎面外科
** 台北榮民總醫院病理科
摘 要
在本文之病例報告中,描述發生於口腔鄰近但不同部位之雙發腫瘤
(double tumors)。病患原先是在另一家醫院就診,被診斷是口腔鱗狀細胞
癌。至本院進行手術後,才發現是兩個不同的腫瘤—口腔鱗狀細胞癌及棘狀
型(acanthomatous type)造釉細胞瘤。我們發現如果單純以H&E染色的顯微鏡
觀察,加上非專精於此領域的醫師來進行診斷,這種雙發性的腫瘤其實也很
容易被誤診。由於本例曾於外院被誤診,我們另外利用免疫螢光染色尋找可
用於鑑別診斷兩種不同腫瘤的工具。結果發現CK8在本病例中之兩種不同的腫
瘤有完全不同的表現。造釉細胞瘤利用CK8染色呈現中度至強度的免疫反應,
而口腔鱗狀細胞癌則完全無反應。另外再取20例造釉細胞瘤及15例口腔鱗狀
細胞癌進行CK8的染色,仍有相同的結果,顯示CK8有助於顯微鏡下難辨之造
釉細胞瘤及口腔鱗狀細胞癌之鑑別診斷。
關鍵詞:造釉細胞瘤,cytokeratin 8,口腔鱗狀細胞癌。
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