Open Journal of Stomatology, 2011, 1, 114-120 OJST
doi:10.4236/ojst.2011.13018 Published Online September 2011 (
Published Online September 2011 in SciRes.
Extraosseous Ewing’s sarcoma arising from the
pterygomandibular space
Wei Li, Jian Tao Huang, Xiao Qing Chen, Rong Hua Shi, Lei Jiang, Yun Fu Zhao*
Department of Stomatology, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Email: *
Received 17 July 2011; revised 25 August 2011; accepted 3 September 2011.
Extraosseous Ewing’s sarcoma (EES) arising in head
and neck is extremely rare. We report on a rare case
of EES originating from the pterygomandibular
space. A 15-year-old boy was seen with a rapidly
growing mass in the right upper neck, difficulty in
opening mouth, dysphagia, numbness in the right
lower lip and buccal skin. Clinical and radiological
examinations indicated that a soft tissue mass origi-
nated from the pterygomandibular space with the
submandibular space and mouth floor extension.
Histological and immunohistochemical evaluations of
the biopsy specimen revealed poorly differentiated
small blue round cells with positive stains for CD99
and neuron-specific enolase. According to the clinical
manifestation, CT and MRI findings, histological
pattern and the results of the immunohistochemical
studies, the final diagnosis was EES. Our patient
was treated with chemotherapy and radiotherapy.
The lesion recurred locally after 10 months and he
died of multiple distant metastases 22 months later.
Early and confident diagnosis coupled with com-
bined surgical excision and modern chemother-
apy/radiotherapy appears to be the most effective
treatment plan.
Keywords: Extraosseous Ewing’s Sarcoma;
Pterygomandibular Space; Di agnosis; Radiotherapy
Ewing’s sarcoma (ES) of bone was first described by
James Ewing in 1921 [1]. ES most commonly arises in
the skeleton of adolescents and young adults, and about
15% are extraosseous. This rare subset of ES, known as
extraosseous Ewing’s sarcoma (EES), was first reported
by Tefft et al. in 1969 [2]. It arises in soft tissue and
shares histological, immunohistochemical, and molecu-
lar findings with bone ES. EES occurs predominantly in
adolescents and young adults between the ages of 10 and
30 years, and follows an aggressive course, with a high
recurrence and metastasis rate. In a clinicopathological
study of 39 cases of EES reported by Angervall and
Enzinger [3], the paravertebral region was the most fre-
quent site of involvement, followed by the lower ex-
tremity and chest wall.
EES arising in the head and neck is extremely rare.
Although it has been reported in the orbit [4], scalp [5],
face [6], nasal cavity [7], paranasal sinus [8], nasophar-
ynx [9], parapharyngeal space [10,11], larynx [12], hard
palate [13], submandibular gland [14], parotid gland [15],
thyroid gland [16] and soft tissue of the neck [17], to our
knowledge, there has been no documented case regard-
ing involvement of the pterygomandibular space by EES.
This article reports a rare case of EES originating from
the pterygomandibular space with the submandibular
space, mouth floor extension and describes the clinical,
radiological, histopathological and immunohistochemi-
cal features.
In June 2009, a 15-year-old boy presented to our de-
partment with a 3-month history of a mass in the right
upper neck that had rapidly increased in size. One month
before seeking treatment, he had developed difficulty in
opening mouth, dysphagia, numbness in the right lower
lip and buccal skin. His personal history and his family
history were not contributory, and no apparent history of
trauma around t he ri ght u pper neck was noted.
Clinical examination was remarkable for the right
submandibular mass measuring 5 × 7 cm (Figure 1(a)).
The mass was rubbery, mild tenderness, and fixation to
underlying structures. The overlying skin was of normal
texture and color. No palpable cervical lymphadenopa-
thy was present. Maximal mouth opening was 20 mm.
The intraoral examination revealed a large submucosal
bulge in the floor of mouth, pushing the right tongue
oppositely, however, the tongue motion was preserved.
The swelling was covered with ulcerated-appearing
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
11 5
muc osa (Figure 1(b)). All lower right teeth tested vital
to electrical pulp testing. Chest radiograph and ab-
dominal ultrasonography were normal. The laboratory
data, including the alkaline phosphatase and lactic acid
dehydrogenase level, were within normal limits.
Computed tomography (CT) examination showed a
well-circumscribed solid mass, measuring about 9 × 7 ×
9 cm, occupying the right pterygomandibualr, subman-
dibular space and mouth floor, which exhibited hetero-
geneous post-contrast enhancement. Localized erosion
and periosteal reaction of the lingual cortex of the man-
dible w as a lso no t ed on CT scan . No ev id en ce w as found
of calcification, lytic appearance or medullary involve-
ment (Figure 1(c)). Magnetic resonance imaging (MRI)
examination was performed to demonstrate the extension
of the lesion and surrounding tissue involvement. T1, T2
and contrast-enhanced T1-weighted images indicated
that a well-circumscribed soft tissue mass closely at-
tached to the lingual cortex of the ascending ramus and
extension into the pterygomandibular, submandibular
space and mouth floor (Figure 1(d)). The mass was hy-
pointense to isointense on T1-weighted and heterogene-
Figure 1. (a) Clinical photography of the patient at time of
initial presentation. Notice the large swelling in the right sub-
mandibular region. (b) Intraoral examination showing a large
submucosal bulge with ulcerated-appearing mucosa in the right
mouth floor. (c) Axial contrast-enhanced (soft tissue window)
computed tomography scan showing a well-defined, with het-
erogeneous contrast-enhanced mass, partially encircling cortex
of bone. A variable periosteal “sun-ray” reaction (arrow) of the
lingual cortex of the mandible can be seen. No signs of lytic or
medullary involvement are seen. (d) Coronal T1 weighted MRI
showing a well-circumscribed soft mass, occupying the right
pterygomandibualr, submandibular space and mouth floor.
ously hyperintense on T2-weighted scans. On con-
trast-enhanced T1-weighted images, the lesion showed
heterogeneous signal increase with internal hypointense
necrotic areas.
In view of the imaging findings, a submandibular in-
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
cisional biopsy was carried out. At surgery, the lesion
was found to be tightly enveloped in a thin layer of
pseudocapsule. Histopathologic examination of the bi-
opsy specimen revealed poorly differentiated small blue
round cells with oval nuclei and scanty cytoplasm (Fig-
ure 2(a)). A panel of immunohistochemical stains was
performed. The tumor cells were positive for CD99
(Figure 2(b)) and neuron-specific enolase (NSE) (Fig-
ure 2(c)) and negative for leukocyte common antigen
(LCA), CD30, CD20, myosin, actin, and myoglobulin,
neurofilament (NF), and the S-100 protein, vimentin,
synaptophysin (Syn). The CD99 stain exhibited strong
membranous staining. The clinical manifestation, CT
and MRI findings, histological pattern and the results of
the immunohistochemical studies were compatible with
According to the extent of the tumor and particular
anatomy site, the patient’s parents refused radical sur-
gery. Chemotherapy and radiotherapy were planned. At
first the patient was treated with one cycle of multiagent
chemotherapy (cyclophosphamide 750 mg, adriamycin
50 mg and vincristine 2 mg, actinomycin D 0.6 mg) and
followed by radical radiotherapy. The total dose of 7000
cGy was delivered in 200 cGy fractions, five times per
week. The patient appeared to tolerate chemotherapy
well, achieving some resolution of swelling in the upper
neck and oral cavity. With the subsequent radiotherapy
the patient seemed to acquire complete remission. The
patient remained well for 10 months with no evid ence of
recurrence in the upper neck and oral cavity. Unfortu-
nately, MRI examination revealed that the lesion had
recurred locally and was located at the lingual bone cor-
tex surface of the ascending ramus (Figure 3) and bone
scan showed multiple bone metastases (right femur and
T11, 12 vertebrae). Therefore, a second round of focal
radiotherapy and combination chemotherapy regimen
were discussed with his parents, but they did not accept.
He died of widespread metastases to the bones and lung s
22 months after radiotherapy.
There has been remarkable evolution in the concepts
regarding ES histogenesis and relation with other small
round cell tumors, including peripheral primitive neu-
roectodermal tumor (pPNET). The relationship between
EES and pPNET represents one of the most fascinating
controversies in pathology. Both EES and pPNET show
varying degree of neuroectodermal differentiation [11].
The term EES has been used for those tumors that lack
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
11 7
Figure 2. (a) Photomicrograph showing compactly arranged small blue and round undifferentiated
cells with great uniformity (hematoxylin-eosin stain, original magnification × 40). (b) The tumor
cells showing intense membranous staining with CD99 antibody (original magnification × 40). (c)
Many tumor cells showing positive staining for antibodies against neuron-specific enolase (original
magnification × 40).
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
Figure 3. Coronal T2 weighted MRI showing a recurrent lesion (arrow) on outer surface of lin-
gual cortex of the right ascending ramus.
neuroectodermal differentiation by light microscopy,
immunohistochemistry and electron microscopy [18].
pPNET shows neuroectodermal differentiation, with
rosette formation and immunohistochemical staining for
nucleus including neuron specific enolase (NSE), neuro-
filament (NF) and synaptophysin (Syn) .Currently they
are categorized into a group known as the Ewing sar-
coma family of tumors (ESFT) which includes classic
ES of bone, EES, Askin tumors of the chest wall and
pPNET of bone or soft tissues. ESFT exhibits a unique
karyotypic abnormality of t (11; 22) (q24; q12) translo-
cation, resulting in the expression of a new chimeric
EWS-FLI1 protein. This genetic abnormality can be
identified in nearly 90% of ESFTs. Expression of the
MIC2 gene in a majority of these tumors is important
from a diagnostic point of view. Although MIC2 is not
specific for ESFTs and is expressed in a wide range of
unrelated tumors, stain with CD99 (product of the MIC2
gene) provides support for the diagnosis of these tumors,
if used with other features. Identification of the fusion
transcripts EWS/FLI1 or EWS/ERG by RT-PCR or fluo-
rescent in situ hybridization serves as a sensitive and
specific diagnostic test for ESFT [19].
It is not easy to diagnose EES by focusing only on
histologic studies, due to its similarity to the rest of the
small round cell tumors. Immunohistochemical stains,
especially CD99, improve the diagnostic certainty. CD99
is a cell surface glycoprotein found in virtually all
ESFTs. Although some other small round cell tumors
such as neuoblastoma, lymphomas, and embryonic and
alveolar rhabdomyosarcoma may also occasionally show
positive staining for CD99, they are excluded by other
immunohistochemical stains. Lymphoblastic lymphoma
and rhabdomyosarcoma can be excluded by negative
staining for LCA, CD30, myosin, actin, and myoglobu-
lin. Neuroblastoma can be excluded by negative staining
for NF, NSE, and the S-100 protein. Lack of neurose-
cretory type granules (NFs) separates classic ES from
pPNET [20]. In addition, the majority of rhabdomyo-
sarcomas, neuroblastomas, and osteosarcomas are ane-
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
11 9
uploid, whereas Ewing’s sarcomas are usually diploid
[21]. In our case, tumor cells showed no rosette forma-
tion and were negative on immunohistochemical stains
for LCA, CD30, CD20, myosin, actin, and myoglobulin,
NF, S-100 protein, vimentin, Syn. The tumor cells only
showed positive stain ing fo r CD99 and NSE. Our patient
was diagnosed with EES based on the results of exten-
sive immunohistochemical staining as described above.
EES arising in head and neck is extremely rare and
only some cases have been reported in the orbit, scalp,
face, nasal cavity, paranasal sinus, nasopharynx, para-
pharyngeal space, larynx, hard palate, submandibular
gland, parotid gland, thyroid gland, and soft tissue of the
neck [4-17]. However, no case originating from the
pterygomandibular space has been reported to date.
Clinically, about 75% of the patients with EES present
with a rapidly enlarging swelling which is usually less
painful than its osseous counterpart, 30% patients exhib-
iting distant metastasis at the time of diagnosis [22]. It
has a high propensity to spread locally, infiltrating sur-
rounding fascial planes and invading muscle and bone.
Our patient presented with a rapidly growing mass in the
submandibular region and oral cavity associated with
mild tenderness, restriction of mouth opening, dysphagia,
numbness in the right lower lip and buccal skin but did
not have any signs of distant metastasis. These clinical
findings suggested th at the internal pterygoid muscle and
mandibular branch of the fifth cranial nerve had been
involved in the tumor spread.
CT and MRI are frequently used in the radiological
evaluation of ESFTs of the head and neck. However,
these modalities cannot provide a specific diagnosis, but
successfully demonstrate the internal structure of the
lesion and the extent of the tumor. Most tumors appear a
diffusely enhancing soft tissue mass on CT. On MRI,
these tumors are generally of hypointense to isointense
on T1 weighted images, of hypointense to hyperintense
on T2 weighted images, and exhibit heterogeneous con-
trast enhancement. Spontaneous tumor haemorr hage and
regional metastatic adenopathy have been demonstrated
in some cases using MRI or CT, but no evidence of tu-
moral calcification prior to treatment has been reported.
However, the key differences in osseous ES and EES are
obvious on CT and MRI. Radiologically, osseous ES is
essentially destructive lesion with ill-defined margins
and principally involves the medullary cavity. The most
common radiologic signs are bone expansion and lytic
changes. Although EES is a primary tumor of soft tissue
and tends to spread locally, it usually has a pseudocap-
sule on gross specimen and thus appears well-
circumscribed on CT or MRI. It can cause changes in the
cortex of adjacent bone. These radiological characteris-
tics are consistent with those found in our case.
The rarity of EES makes it difficult to ascertain an op-
timal management for those tumors. However, better
results seem to correlate with more aggressive combina-
tion of surgery plus radiotherapy plus chemotherapy.
Although there is some debate about the management of
EES compared with bone ES, it is clear that all members
of the ESFT share the propensity for recurrence and me-
tastasis. Treatment is fundamental in the local control of
the disease in its primary location, using radical surgery
or radiotherapy, and the systemic control of subclinical
micrometastasis with chemotherapy. Surgery is the treat-
ment of choice for the local control of the disease if the
tumor can be completely resected. The indications for
surgery should be carefully considered in each patient
with regard to age and location, size, extension, and re-
sectability of the primary tumor, also taking into account
the deformity and surgical morbidity that can be pro-
duced. EES is radiosensitive. However, the role of ra-
diotherapy is still under debate. In general, radical or
adjuvant radiotherapy should be reserved for initially
unresectable lesions or residual disease. Rud et al. were
the first to report on the importance of multiagent che-
motherapy in the treatment of patients with EES [23]. In
Whaley’s report, combined modality therapy provides
excellent local control with reasonable acute and late
toxicity [17]. Although the optimum combination che-
motherapy is yet to be established, a four drug regimen
using vincristine, adriamycin, cyclophosphamide and
actinomycin D (VACA) is considered as the standard
first-line treatment for patients with localized disease
[24]. We used neoadjuvant chemotherapy after confir-
mation by biopsy to shrink the tumor mass and control
possible occult distant metastasis and then radical radio-
therapy. He responded well to the regimen of chemo-
therapy and radiotherapy. Unfortunately, the lesion re-
curred locally after 10 months, he died of multiple dis-
tant metastases 22 months later.
EES arising in head and neck is extremely rare. Rapid
growth and propensity for recurrence and metastasis are
dominant features of this primary malignant soft tissue
tumor. It is not easy to diagnose EES by focusing only
on histological studies. Although MIC2 is not specific
for EES and is expressed in a wide range of unrelated
tumors, stain with CD99 provides support for the diag-
nosis of EES, if used with other features. CT and MRI
cannot provide a specific diagnosis, but successfully
demonstrate the internal structure of the lesion and the
extent of the tumor. The diagnosis of EES in our case
was based on clinical, radiological, histological and im-
munohistochemical findings. Early and confident diag-
nosis coupled with combined surgical excision of gross
W. Li et al. / Open Journal of Stomatology 1 (2011) 114-120
Copyright © 2011 SciRes. OJST
disease and modern chemotherapy/radiotherapy appears
to be the most effective treatment plan.
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