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Otolaryngology Case Reports
journal homepage: www.elsevier.com/locate/xocr
A rare case of primary Ewing's sarcoma presenting in the posterior nasal
cavity with extension into the sphenoid sinus and a review of the literature
Koorosh Rahmani, Shokouh Taghipour zahir, Mohammad Baghi Yazdi
∗
,
Mohammad-hossein Vahedian-Ardakani, Maryam Vajihinejad
Shahid Sadoughi University of Medical Sciences, Yazd, Iran
ARTICLE INFO
Keywords:
Neuroectodermal tumors
Primitive
Metastasis
Brain
Nose
ABSTRACT
Ewing's sarcomas/primitive neuroectodermal tumors (PNET) are a group of tumors characterized by small round
cells that rarely affect the bone and soft tissues of the nasal cavities. Herein, we describe the case of a 38-year-old
man who presented with a one-year history of epistaxis, headache, hyposmia, anosmia, night sweats, weight loss,
hearing loss, dysphagia, and nasal blockage. A computed tomography (CT) scan and magnetic resonance ima-
ging (MRI) studies revealed a lesion in the posterior nasal cavities with extension into the sphenoid and ethmoid
sinuses. Histological examination of a biopsied specimen obtained via flexible fiberoptic endoscopy showed
small dark round cells with scanty cytoplasm arranged in solid nests and pseudorosette formations. The diag-
nosis of Ewing's sarcoma was confirmed by the positive reactive pattern of the neoplastic cells for CD99 by
immunohistochemistry studies and also identification of a chromosomal translocation of FLI1 in PCR studies.
Cervical lymph nodes and bone marrow involvement were also observed. The patient was treated by adjuvant
chemotherapy including vincristine, endoxan, and adriamycin for 6 cycles followed by radiotherapy (eleven
courses). Unfortunately, before completion of treatment, the patient died due to disease progression and brain
metastasis.
Introduction
Ewing's sarcomas/primitive neuroectodermal tumors (PNET) are
rare tumors characterized by small round cells that mainly affect bone
and soft tissues in children and young adults [1,2]. The most common
bones affected by the neoplastic cells are the pelvis, femur, humerus,
ribs, and clavicle bones [2,3]. However, bone involvement in patients
over 30 years old is rare, and involvement of the nasal cavity by Ewing's
sarcomas/PNET tumors is extremely rare and only a few case reports
have been published [4–6]. Herein, we present a case of Ewing's sar-
coma arising in the nasal cavity with extension into the ethmoid and
sphenoid sinuses with secondary bone marrow involvement.
Case presentation
A 38-year-old man came to our otorhinolaryngology clinic with a
one-year history of epistaxis, headache, hyposmia, anosmia, night
sweats, weight loss, hearing loss, dysphagia, and nasal blockage. On
physical examination, numbness of both cheeks was evident.
Laboratory tests revealed anemia with red blood cell count 3.03 × 10
6
/
ml (normal range, 3.6–6.1), hemoglobin level of 7.5 mg/dl (normal
range 11.5–18.8 g/dl), hematocrit, 26.5% (normal range 34–54%), and
platelet count 143 × 103/ml (normal range, 165–415).
An axial view of a neck computed tomography (CT) scan with in-
travenous contrast showed a soft tissue mass with punctuate calcifica-
tion in the ethmoid and sphenoid sinuses with extension into the nasal
cavities. On the sagittal view, involvement and destruction of the clivus
was evident, and on the coronal view, erosion of the medial wall of the
left orbit was seen (Fig. 1A, B). Mucosal thickening and retention cysts
in both maxillary sinuses with left osteomeatal complex obstruction
(OMC) was present. Multiple hypodense lymph nodes (necrotic) were
seen on both sides in the anterior and posterior cervical lymphatic
chains, the largest one being around 23 ×25 mm in zone 2 on the left
side. A cranial MRI, without contrast, using axial, sagittal, and coronal
views on T1-weighted images (T1WI), showed a heterogeneous mildly
hyper signal nasopharyngeal mass measuring about 51 × 56 × 30 mm
that was occupying both sides of the ethmoid and sphenoid sinuses and
superior part of the nasal cavities. Erosion of the medial wall of the left
orbit and clivus was evident (Fig. 2A, B, C). Obstruction of bilateral
Eustachian tubes caused mastoiditis and bilateral OMC caused retention
https://doi.org/10.1016/j.xocr.2018.01.003
Received 17 November 2017; Accepted 9 January 2018
∗
Corresponding author. Student of Medicine, School of Medicine, Shahid Sadoughi University of Medical Sciences, Professor Hessabi 11 BLV, Shohadaye Gomnam BLV, P.O.
8915173149, Yazd, Iran. Fax: +98 351 8202632.
E-mail address: drbaghi7272@yahoo.com (M.B. Yazdi).
Otolaryngology Case Reports 6 (2018) 34–37
Available online 10 January 2018
2468-5488/ © 2018 Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
T
of secretions in both maxillary sinuses. Multiple hypo signals on T1W1
and hyper signal lesions on T2W1 were seen in the upper zone of the
neck bilaterally, suggestive of necrotic lymph nodes. The patient un-
derwent flexible fiberoptic endoscopy, but because of the widespread
extension of the mass, only biopsy without complete resection was
performed. Histologically, the tumor consisted of small dark round cells
with scanty cytoplasm that were arranged in solid nests and pseudo
rosette formations with vascular connective tissue between the neo-
plastic nests (Fig. 3A, B). Immunohistochemical (IHC) studies revealed
diffuse positivity for CD99, and Vimentin, and patchy positivity for S-
100 protein (Fig. 4A, B, C). The neoplastic cells were negative for pan-
cytokeratin, NSE, leukocyte common antigen, synaptophysin, and
chromogranin A. On periodic Acid-Schiff(PAS) staining, the neoplastic
cells had positive cytoplasmic staining results that confirmed the gly-
cogen content of the cytoplasm. In molecular studies (PCR)
chromosomal translocation of FLI1 was identified. Thus, a diagnosis of
primary Ewing's sarcoma/PNET of the nasal cavity was confirmed. For
staging of the tumor, bone marrow aspiration and a biopsy were per-
formed. Histopathological and cytological examinations revealed
marrow involvement by neoplastic cells (Fig. 5). Cerebrospinal fluid
cytology was negative for neoplastic cells.
Treatment and follow-up
Because the tumor had an intracranial extension with bone marrow
metastases, surgical resection was not feasible. Adjuvant chemotherapy
followed by radiotherapy was selected. A chemotherapy protocol
composed of vincristine (2 mg, D1), endoxan (1500 g, D1), and adria-
mycin (50 g, D2) was administered for 6 cycles. After chemotherapy,
the patient was scheduled to undergo radiotherapy (54 Gy) for eleven
Fig. 1. A: Sagittal view CT scan demonstrates destruction of the
clivus. B: The coronal view shows erosion of the medial wall of the
left orbit.
Fig. 2. A, B, C: T1-weighted image (T1WI), shows a heterogeneous mildly hyper signal nasopharyngeal mass that is occupying both sides of the ethmoid and sphenoid sinuses and
superior part of the nasal cavities. Erosion of the medial wall of the left orbit and clivus is evident.
Fig. 3. A, B: Small dark round cells with scanty cytoplasm
that are arranged in solid nests and pseudo rosette forma-
tions within fibrovascular connective tissue, (H&E staining,
magnification ×10, ×20).
K. Rahmani et al. Otolaryngology Case Reports 6 (2018) 34–37
35
courses. Unfortunately, before completion of treatment, the patient
died due to disease progression and the development of brain metas-
tasis.
Discussion
Ewing's family of tumors (EFT) includes PNET and Ewing's sarcoma
that are characterized by small round cells, first described by Arthur
Purdy Stout in 1918 in the ulnar nerve and later named Ewing's sar-
coma by James Ewing in 1921, describing a tumor located in the long
bones [1,2]. In around 85% of cases a translocation between genes 22
and 11 is seen that causes fusion of the EWS gene on chromosome 22 to
the FLI1 gene on chromosome 11 [3,4]. PNET/Ewing's sarcoma tumors
mostly affect children and young adults with a male preponderance
(1.6:1). Ewing's sarcoma usually originates from the diaphysis or me-
taphysis of long bones, pelvic bones, and ribs [1,2]. Rarely, the skull
bones, the vertebrae, the scapula, and the small bones of hands and feet
are the origin of the tumor [5]. Although involvement of the head and
neck bones is uncommon, primary Ewing's sarcoma of the paranasal
sinuses is extremely rare [2,3,5]. In EFTs, the neoplastic cells have a
dark hyperchromatic nuclei and scanty cytoplasm with indistinct
boundaries, arranged in sheets and some rosette formations with areas
of necrosis. The cytoplasm of the neoplastic cells contains glycogen and
is positively stained by PAS showing diastase resistance [1–3]. The
neoplastic cells have a strongly positive reaction pattern for CD99
(MIC2), a diffuse positive pattern for vimentin and S-100, and a nega-
tive reaction pattern for CD45, desmin, NSE, HMB-45, and myogenin
antibodies on IHC staining. NSE is a questionable IHC marker for
Ewing's sarcoma family tumors, because in some literature, in-
vestigators mentioned that NSE was negative in neoplastic cells [4,6]
and others reported a positive reaction for NSE in their case, such as
Hafezi et al. [3] On imaging, the differential diagnosis of sinonasal
malignant lesions could include: sinonasal carcinoma (squamous cell
carcinoma or adenocarcinoma), sinonasal lymphoma, esthesioneuro-
blastoma, and much less likely Ewing family tumors (sarcoma/PNET)
[7]. Suzukia et al. [8] reported a case of primary Ewing's sarcoma of the
sinonasal with ethmoid sinus involvement without bony erosion or
brain extension, which is different from our case, which had bone
erosion and brain extension. In the histopathological differential diag-
nosis, non-keratinized squamous cell carcinoma, esthesioneuro-
blastoma, malignant lymphoma, undifferentiated carcinoma, Ewing's
sarcoma, and rhabdomyosarcoma could be considered [9–11]. Esthe-
sioneuroblastoma was considered unlikely in our case, because it ori-
ginates from an anterior area of the nasal cavity and cribriform plate,
and in our patient the mass originated from the posterior of the nasal
cavity [1,4]. Also, neoplastic cells in esthesioneuroblastoma have a
diffuse staining pattern for NSE, synaptophysin, and chromogranin A,
but negative staining for CD99 and desmin [5,11]. Rhabdomyosarcoma
cells have a negative reactive pattern for CD99 and also exhibit the
characteristic histomorphology of rhabdomyoblasts [8,9]. In un-
differentiated carcinoma, neoplastic cells have a larger nucleus, are
arranged in a solid nest pattern, and stain positive for pan-cytokeratin
without a positive reaction for CD99 [9,12,13]. In malignant lym-
phoma, neoplastic cells stain positive for CD45 [12]. The clinical pre-
sentation of sinonasal involvement is variable depending on tumor size
and extension of tumoral cells to adjacent bones and soft tissues, and
includes symptoms such as headache, nasal congestion, epistaxis, hy-
posmia, anosmia, facial pain, and also the loss of teeth [4,8,10]. Sec-
ondary bone marrow involvement is rare but can be seen late in the
course of the disease. Ewing's sarcoma has an aggressive behavior and
early metastasis to distant sites such as bone marrow, which occurred in
our patient [8]. Surgery and chemotherapy followed by radiotherapy
are the treatments of choice although if there is widespread extension of
the tumor and distant metastasis surgical treatment is limited and there
is an ominous outcome [9,11].
Our presented case is unique because of the clinical presentation,
imaging features (bone destruction), and simultaneously bone marrow
involvement with anemia early in the course of tumor presentation.
Tajima et al. (2015) [14] reported a better prognosis and overall sur-
vival for extramedullary Ewing's sarcoma, but in contrast to their case,
our patient had an ominous outcome and due to widespread
Fig. 4. A: Neoplastic cells have a positive reaction pattern for CD99 (immunostaining, magnification ×40). 4B: positive reaction pattern of neoplastic cells for vimentin (immunostaining,
magnification ×20). 4C: Scattered positive reaction pattern for S-100 protein (immunostaining, magnification ×20).
Fig. 5. Involvement of bone marrow by neoplastic cells which have a small round hy-
perchromatic nuclei, arranged in nests pattern (H&E staining, magnification ×20).
K. Rahmani et al. Otolaryngology Case Reports 6 (2018) 34–37
36
dissemination of the tumor did not respond to therapy and passed away
[14].
Conclusion
Although Ewing's sarcoma mainly involves the pelvis, femur, hu-
merus, and rib bones of children and young adults, very rarely it can
involve the nasal cavity and sinuses and show aggressive behavior.
Immunohistochemical studies help in the differentiation Ewing's sar-
coma from other dark small round cell tumors such as rhabdomyo-
sarcoma, malignant lymphoma, and undifferentiated carcinoma. In
cases where a distant metastasis has already developed at the time of
the initial diagnosis, the response to the treatment is unlikely to be good
and the prognosis is ominous.
Ethical statement
In this manuscript there is no personal information of patient in
figures. There is no face of patient in this manuscript.
Conflicts of interest
There is no conflict of interest.
Acknowledgement
Authors would like to thanks Dr Mohammadali Aghaei-meibodi
(otorhinolaryngologist) and Dr Saeed Tavana (radiologist) for their
useful guidance.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://dx.
doi.org/10.1016/j.xocr.2018.01.003.
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