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放射治療與腫瘤學 Therapeut Radiol Oncol 2016; 23(2): 129-135
129
CarCinosarComa ex PleomorPhiC adenoma
of the Parotid Gland: a Case rePort
Chun-Chieh Wu1, Ying-Hsiang Chou1,2, Yu-Ting Wang3, Yueh-Chun Lee1,4, Hsien-Chun Tseng1,5
Department of Radiation Oncology1, Department of Pathology3, Chung Shan Medical University Hospital
School of Medical Imaging and Radiological Sciences2, Institute of Medicine4, School of Medicine5,
Chung Shan Medical University
Pleomorphic adenoma of the parotid gland is the most common tumor of the
salivary glands. Although very rare, this tumor can undergo malignant transformation,
resulting in carcinosarcoma ex pleomorphic adenoma, which possesses the characteristics of both carcinoma and sarcoma. In the literature, the number of such cases
is very low and the treatment outcomes are varied. Surgery remains the primary local
treatment. Radiotherapy may be added to enhance local-regional control. Here, we
present a 45-year-old male who underwent surgical removal of pleomorphic adenoma
of the right parotid gland twice. He was eventually diagnosed with carcinosarcoma ex
pleomorphic adenoma. Treatment consisted of superficial parotidectomy and adjuvant
concurrent chemoradiation with weekly cisplatin and a radiation dose of 66 Gy. After
30 weeks of follow-up, no disease recurrence or distant metastasis was observed.
[Therapeut Radiol Oncol 2016; 23(2): 129-135 ] DOI: 10.6316/TRO/201623(2)129
Key words: Carcinosarcoma, Pleomorphic adenoma, Parotid gland, Radiotherapy
introdUCtion
Pleomorphic adenoma is the most
common benign tumor of the salivary glands.
Only about 3-4% of these tumors undergo
malignant change [19]. Malignant transformation of pleomorphic adenoma follows 3
patterns: carcinoma ex pleomorphic adenoma,
metastasizing benign pleomorphic adenoma
and carcinosarcoma ex pleomorphic adenoma,
with the latter 2 being extremely rare [11].
Carcinosarcoma is also called t r ue
malig nant mixed t u mor. By def i nition,
carcinosarcoma is composed of both epithel ial (ca rci nomatou s) a nd mesenchy mal
(sarcomatous) components. It mainly occurs
in the elderly; mean age at diagnosis is 58
years with similar prevalence in both sexes. It
usually arises in the major salivary glands with
associated symptoms of swelling, pain and
facial palsy. The clinical behavior of carcinosarcoma is aggressive and the tumor growth is
rapid. The prognosis of carcinosarcoma is poor
with a mean survival of 2.5 to 3.6 years [6].
Since carcinosarcoma ex pleomorphic
adenoma over salivary glands is very rare,
there is no consensus in terms of the treatment
protocol globally. Here, we present a case of
carcinosarcoma ex pleomorphic adenoma over
right parotid gland treated with superficial
Received: 2015, 11, 30. Accepted: 2016, 1, 11.
Address reprint request to: Hsien-Chun Tseng, MD. Ph.D., Department of Radiation Oncology, Chung Shan Medical University
Hospital., No.110, Sec.1, Jianguo N. Rd., Taichung City 40201, Taiwan, R.O.C.
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Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland
parotidectomy and adjuvant concurrent chemoradiotherapy. The current literature regarding
the treatment options and prognosis of this
disease was reviewed.
Case rePort
In August 2009, a 45-year-old male
presented with the chief complaint of a fixed
mass with swelling sensation over the right
parotid region at our hospital. Neither facial
palsy nor facial numbness was noted at that
time. After tumor removal by a surgeon, pleomorphic adenoma was diagnosed (Fig 1A). In
March 2012, another episode of painful swollen
mass over the right parotid region occurred and
he received repeat surgical excision. Recurrent
(A)
(D)
(B)
pleomorphic adenoma was diagnosed. During
regular follow-up after the second surgery,
residual tumor over the right parotid gland was
suspected. The patient refused further surgical
intervention, but agreed to follow up MRI
every 3 months.
The residual tumor grew into an 8-cm
mass. Physical examination revealed a firm
mass with local swelling, without tenderness,
facial palsy, or facial numbness. CT scan
demonstrated a 69 x 47 x 58 mm, lobulated,
cystic lesion within the superficial lobe of
the right parotid gland, as well as regional
subcutaneous fat stranding. Under the impression of residual pleomorphic adenoma with
progression, right superficial parotidectomy
was carried out. The pathology report revealed
(C)
(E)
Fig 1. The histological features of R’t parotid tumors in this 45 years old male. (A) Benign pleomorphic
adenoma: It composed of ductal cells, myoepithelial cells and fibrous to chondroid stroma. (H&E; x 40)
(B) Carcinosarcoma: The tumor reveals a biphasic appearance composed of an epithelial component
(arrow) with variably sized nests and an intervening spindle cell component (split arrow). (H&E; x 100)
(C) Malignant epithelial component: Enlarged right parotid gland (69 x 47 x 58 mm) with large lobulated
cystic lesion (within superficial lobe) and relatively mild regional subcutaneous fat stranding. (H&E; x
100) (D) Malignant sarcomatous component: It displays pleomorphic spindle or fusiform cells set in
variably collagenized stroma or myxoid stroma. (H&E; x 200) (E) CK (AE1/AE3) immunostaining: The
epithelial component is positive for CK and negative for sarcomatous components (H&E; x 100)
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Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland
carcinosarcoma ex pleomorphic adenoma,
intermediate grade (G2), measuring 4.5 x 4.0
x 3.2 cm. The surgical margins were 1 mm
and negative for lymphovascular or perineural
invasion. The diagnosis of carcinosarcoma was
based on the biphasic population of epithelial
and mesenchymal cells, as well as the immuneprofiles (Fig 1B-D). The tumor was positive
for cytokeratin (CK), P16, S100, vimentin and
negative for CK5/6, P63, Desmin, HK, CK14,
CD34, Calponin, Myogenin (Fig 1E). The
pathological staging was pT3Nx.
No cancer survey was conducted prior to
the surgery. PET-CT was arranged post-operatively for staging work-up. No abnormal hypermetabolic foci consistent with regional lymph
node metastases or distant metastases were
identified. Although radical parotidectomy
was indicated for malignant parotid tumor with
close margin, the patient refused reoperation.
After providing a thorough explanation to
the patient, he received adjuvant concurrent
chemoradiotherapy (CCRT). The regimen for
chemotherapy was weekly cisplatin (Kemoplat) 35mg/m 2 for 6 cycles. Radiotherapy was
delivered with a 6 MV linear accelerator by
photon beam using intensity-modulated radiotherapy (IMRT) techniques (Elekta Synergy®)
once per day, 5 fractions per week. The radiation fields included the initial tumor bed as
clinical target volume-medium (CTV-M) and
ipsilateral submandibular nodes, upper jugular
nodes, middle jugular nodes, retropharyngeal nodes and parotid node group as clinical
target volume-low (CTV-L). The clinical target
volumes were expanded by 3mm to create
planning target volumes PTV-M and PTV-L.
The PTV-M received 66 Gy in 33 fractions
and the PTV-L received 50.4 Gy in 28 fractions. Treatment planning was carried out with
Philips’ Pinnacle 3 RTP system version 9.0.
Cone-beam computed tomography was used
for daily position correction. During CCRT,
acute treatment-related sequelae included
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grade 1 radiation dermatitis and pharyngitis
according to RTOG criteria.
The patient received regular follow-up
after CCRT with complete physical examination at every visit and MRI every three months.
Abdominal ultrasonography and chest X-ray
were also performed every 6 months. The
patient was followed up for 30 weeks after
CCRT with no evidence of tumor recurrence.
disCUssion
Clinical features
About half of salivary gland tumors are
pleomorphic adenomas, which are also called
benign mixed tumors [15]. The most common
site for pleomorphic adenoma is the superficial lobe of the parotid gland. The choice of
treatment for parotid pleomorphic adenoma
is superficial parotidectomy, which reduces
the risk of recurrence to less than 5%. Other
surgical techniques, such as simple enucleation, result in a 20-45% local recurrence
rate. Total parotidectomy, a more extensive
procedure, does not further reduce recurrence
rate, but does increase the rates of facial nerve
dysfunction and other complications [9]. Carcinoma ex pleomorphic adenoma is defined as
a carcinoma arising from a primary (de novo)
or recurrent benign pleomorphic adenoma
[14]. This indicates that there is a malignant
transformation component within pleomorphic adenoma. The frequency of malignant
transfor mation increases with increasing
time interval between tumor diagnosis and
treatment. Harada et al. reported that risk of
malignant change increases from 1.5% for
a 5-year interval between tumor diagnosis
and treatment to about 9.5% for a 15-year
interval [8]. Our patient experienced his first
episode of pleomorphic adenoma in 2009. Six
years later, the tumor underwent malignant
transformation.
Carcinosarcoma ex pleomorphic adenoma
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Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland
is a rare entity, resulting from the malignant
transformation of pleomorphic adenoma. It
accounts for one third to one half of all salivary
gland carcinosarcomas, with the remaining
being carcinosarcoma de novo [12]. Salivary
gland carcinosarcoma is a very rare tumor,
which only accounts for 0.4% of all malignant
salivary gland neoplasms and 0.04-0.16% of all
salivary gland tumors [6]. Sixty-seven percent
of salivary gland carcinosarcomas occur in
the parotid glands, 19% in the submandibular
glands, and 14% in the soft palate. By definition, carcinosarcoma is composed of both
epithelial (carcinomatous) and mesenchymal
(sarcomatous) components. The most common
types of carcinoma components are adenocarcinoma, undifferentiated carcinoma and
squamous cell carcinoma. In addition, the
most common sarcomatous components are
chondrosarcoma and osteosarcoma followed
by fibrosarcoma [21]. The differences in the
above in terms of histology, such as prognosis
or survival, are not well known due to the
rarity of these types of tumors. In our case, the
carcinomatous type was squamous cell carcinoma with variably sized nests and intervening
spindle cell components.
Two thirds of patients develop local
recurrence while about half develop distant
metastases. Metastasis to the lung is the most
common [13, 16]. Peterson et al. reviewed 31
malignant parotid mixed tumors and found
that tumor stage, local extension, existence
of facial palsy and tumor grade are important
prognostic factors [17]. In our case, the mass
grew rapidly to 8 centimeters within a year,
indicating the malignant behavior of the tumor.
However, no distant metastasis was found
during the systemic work-up. This case was
only followed up for 30 weeks, and the disease
prognosis may be poor. Distant metastasis
should be taken into consideration during posttreatment follow-up.
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Diagnosis
The term carcinosarcoma ex pleomorphic
adenoma is based on the demonstration of
both true malignant epithelial and mesenchymal components within the pleomorphic
adenoma. The immunochemical panel of this
tumor varies. While the carcinomatous component is usually positive for CK and epithelial
membrane antigen (EMA), the sarcomatous
component is usually positive for vimentin and
S100 [16]. However, in very poorly differentiated tumors, only focal or weak staining of
CK or EMA is observed. In our case, the
tumor was positive for CK in carcinomatous
component and positive for S100 and vimentin
in sarcomatous component.
The malignant transformation of pleomorphic adenoma is quite difficult to identify on imaging studies. Both CT and MRI
are used in the evaluation of head and neck
tumors. MRI is widely accepted due to its
imaging quality with respect to the soft tissue.
In parotid regions, MRI can detect suspected
deep lobe involvement and depict tumor extent
more accurately. CT, on the contrary, has the
benefit of detecting calcification within the
salivary glands. Fan et al. reported using CT
scan to identify calcification of the parotid
mass, which is most frequently seen in parotid
pleomorphic adenoma when compared with
mucoepidermoid carcinomas, schwannomas
and venous malformations [4]. The malignant
features of parotid carcinosarcoma, studied by
Gogas et al., include ill-defined margins and
irregular rim enhancement on CT images [7].
In contrast, Som et al. consider MRI a more
accurate tool for predicting malignant potential
of parotid tumors. On T2-weighted images,
a low to intermediate signal correlates with
73% accuracy in predicting a high-cellular
malignant tumor, while thick irregular rim
enhancement suggests possible malignancy
[19]. In our case, both MRI and CT images
revealed a heterogeneous mass with irregular
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Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland
rim enhancement and ill-defined margin (Fig
2A, Fig 2B). T2-weighted MRI performed
in January 2014 showed a 4-cm irregularly
shaped parotid mass with multiple small cysts
and mild subcutaneous fat infiltration. Eight
months later, follow up CT revealed 7-cm
enlarged parotid mass with irregular rim
enhancement and subcutaneous infiltration.
During this short interval, the mass grew by 3
cm in diameter with more obvious infiltration
to adjacent tissue. Therefore, malignancy was
suspected.
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Due to the rarity of carcinosarcoma ex
pleomorphic adenoma, the treatment strategy
va r ies. Wide su rgical excision is most
commonly accepted as the primary treatment [18]. Ishikura et al. reported a case of
right parotid carcinosarcoma ex pleomorphic
adenoma. Initially, mild pain and facial palsy
were noted. Treatment included parotidectomy and ipsilateral radical neck dissection.
The tumor measured 2.5-cm with histology of
undifferentiated carcinoma and poorly differentiated adenocarcinoma with chondrosarcoma
and osteosarcoma. There was no lymph node
metastasis. After surgery, adjuvant RT (60
Gy) and chemotherapy were applied. The
patient showed no recurrence or metastasis
after a 17-month follow-up [10]. Patnayak et
al. reported another case of parotid carcinosarcoma ex pleomorphic adenoma presenting
with facial palsy and treated with total parotidectomy only. The histology of the tumor was
ductal type adenocarcinoma with malignant
spindle cell tumor and chondrosarcomatus
component. No lymph nodes were involved.
Adjuvant RT was applied. After 2 years of
follow-up, no evidence of disease recurrence
was noted [16]. Anamaria et al. presented
another carcinosarcoma of the parotid gland,
treated with radical surgery and post-operative
radiotherapy. However, the patient died 13
months later due to lung metastasis [1].
In this modern era of cancer treatment,
multidisciplinary treatment is to be considered due to rapid growth and trend toward
metastasis. In our case, the rationale for adjuvant radiotherapy was to decrease the risk
of local recurrence after inadequate surgery
(superficial parotidectomy) with close margin.
(A)
(B)
Treatment strategies
Fig 2. (A) Neck MRI with T2-weighted image, Irregular heterogenous enlarged right parotid gland with multiple
cystic lesions and mild infiltration to adjacent tissue. (B) Neck CT with contrast enhancement, Enlarged
rim enhanced right parotid gland (69 x 47 x 58 mm) with large lobulated cystic lesion (within superficial
lobe) and relatively mild regional subcutaneous fat stranding.
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Carcinosarcoma ex Pleomorphic Adenoma of the Parotid Gland
Carrillo et al. has reported that patients with
poor risk factors could benefit from postoperative RT including high-grade tumors,
facial nerve palsy, advanced stage lesions,
positive surgical margins and/or older age [3].
Fu et al. reported postoperative RT may reduce
local recurrence rate from 54 to 14 percent for
patients having microscopic disease present at
or close to the surgical margin [5]. Based on
the evidence of head and neck squamous cell
carcinoma (HNSCC), the rationale for adding
chemotherapy to radiotherapy was enhancing
locoregional control therefore decreasing risk
of distant metastases. Bernier et al. reported
334 patients with stage III/IV HNSCC postoperatively randomized to post-op RT (66 Gy
in 33 fractions) vs. post-op chemoradiation
with high dose cisplatin (100 mg/m 2 on days 1,
22, 43) showed improve 5-year overall survival
from 40 to 53 percent, 5-year disease-free
survival from 36 to 47 percent and 5-year locoregional control from 69 to 82 percent [2].
In conclusion, here we present a right
side carcinosarcoma ex pleomorphic adenoma,
t reated w it h super f icial pa rot idectomy
followed by CCRT with weekly cisplatin. After
a 30-week follow-up, no recurrence or distant
metastasis was found. Longer follow-up time is
needed to ensure the treatment outcome.
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腮腺上皮肉瘤合併多形性腺瘤：病例報告
吳俊玠 1　周英香 1,2　王昱婷 3　李岳駿 1,4　曾顯群 1,5
中山醫學大學附設醫院　放射腫瘤科 1　病理科 3
中山醫學大學　醫學影像暨放射科學系 2　醫學研究所 4　醫學系 5
腮腺的多形性腺瘤是唾液腺中最常見的良性腫瘤 ，其中有非常少數會轉變為惡性腫瘤 ，而
轉變為惡性腫瘤中 ，轉化為上皮肉瘤是非常罕見的案例 。上皮肉瘤顧名思義是同時具備上皮
癌 ，以及肉瘤的特徵 。在過去文獻報導中個案數相當低 ，並且沒有一致的治療方針 。手術切
除仍是目前治療的主要方式 ，而術後的放射線治療則可以增進其局部控制率 。本篇病歷報告提
出一位 45 歲男性 ，在接受兩次切除右側腮腺多型性腺瘤之後，復發了多型性腺瘤合併上皮肉
瘤 。我們給予手術表淺腮腺切除之後 ，術後執行了同步化學治療合併放射線治療 ，使用每周
cisplatin 的輸注以及 66 Gy 的放射線治療 。病人追蹤 30 周 ，情況良好 ，沒有復發或轉移的現
象。
[ 放射治療與腫瘤學 2016; 23(2): 129-135 ]
關鍵詞：上皮肉瘤 、多型性腺瘤 、腮腺 、放射線治療
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