Ewing’s Sarcoma of Maxillary Sinus

Abstract

Ewing’s sarcoma is a small round cell tumor commonly involving long bones. Head and neck involvement is seen less frequently with maxillary sinus being the rarest site. Here we report a case of a12-year-old female patient presented with left side facial swelling for 3 weeks duration which was diffuse and hard on palpation. CT and MRI of Nose & para nasal sinus revealed a mass lesion in the left maxillary sinus infiltrating and eroding the orbital wall and extending intracranially. Biopsy from the lesion revealed Ewing’s sarcoma with strong positivity for CD-99 marker. Patient was referred to radiotherapy due to extensive disease at younger age. The CT and MRI along with HPE and IHC markers enables early diagnosis and prompt treatment that leads to better survival and prognosis, as unlike Ewing’s sarcoma of long bones, that metastasize early. The combined chemoradiotherapy is now the standard line of treatment along with close follow up for at least 2 years.

Introduction

Ewing’s sarcoma is a malignant, small round cell tumor which arises from the bone. It was first described and identified by James Ewing in 1921 as a perivascular endothelial tumor. It is now believed that this tumor is of neuroectodermal origin that originates from the mesenchymal, myeloid or primitive multipotential cells [1]. These small round cell tumors have many subsets, all of which are referred to as Ewing’s family of tumors that includes Ewing’s sarcoma, peripheral primitive neuroectodermal tumor, neuroepithelioma and Askin tumor [2]. Ewing’s sarcoma mostly arises from the long bones of extremities like femur or humerus accounting for 4–6% of all primary bone tumors [3]. Extra-skeletal Ewing’s sarcoma is rarely seen with head & neck localization accounting for only 1–4% of all cases [4]. Mandible and calvaria are the most common location of Ewing’s sarcoma in the head & neck region with paranasal sinus (PNS) being the rarest. These tumors mostly affect children and young adults, with incidence of tumor after the 3rd decade accounting to only 10% of cases with slight male preponderance [5]. In this article, we report an extremely rare case of an Ewing’s sarcoma of maxillary sinus in a 12 years female patient.

Case Report

A 12-year-old female patient presented to ENT OPD with the chief complaint of swelling over left side of face. (Fig. 1) Her history revealed that the swelling had emerged 3 weeks prior and had been growing increasingly since then. On clinical examination, there was a diffuse swelling over the left maxillary and periorbital region without any signs of inflammation. Swelling was hard on palpation without any fluctuation. Left eye proptosis was evident with medial rectus palsy which was associated with diplopia and blurring of vision. There was fulness in the left medial canthus and left infra-orbital rim was not palpable. Intraoral examination was completely normal. Diagnostic nasal endoscopy (DNE) was done that showed near normal nasal cavity with clear nasopharynx. No other history of nasal discharge/ obstruction or bleeding was present. All the blood parameters were normal. Patient was planned for contrast enhanced computed tomography scan of nose and paranasal sinus (CECT Nose & PNS) with orbit which revealed a homogeneous enhancing soft tissue mass lesion epicentered in the left maxillary sinus extending into the left orbit with resultant proptosis. (Figure 2a and b) Mass was also seen to extend intracranially into the left frontal and temporal region. Due to intracranial involvement, CE magnetic resonance imaging (CE-MRI) of brain with orbit and nose & paranasal sinus was also done that revealed a hyperintense mass lesion measuring approx. 38 × 16 mm involving the left maxillary sinus and intradural extension involving left temporal lobe with extension and encasement of lateral, inferior, superior and inferior oblique muscles of left eye (Fig. 2c and d). Distant metastasis was ruled out using whole body CT scan. In view of high suspicion of malignancy, patient was planned for biopsy from the maxillary sinus. A thickened tissue mass with areas of ulceration was visualized in the left maxillary sinus. Multiple deeper bits of punch biopsy were taken and sent for histopathological examination (HPE) which showed multiple small, uniform round cells with high nucleus to cytoplasmic ratio with warse chromatin and scanty cytoplasm. (Fig. 3a) Later, immunohistochemistry (IHC) of specimen was done that showed positive tumor expression for CD-99 marker (Fig. 3b). Histopathology and immunochemistry confirmed the diagnosis of Ewing’s sarcoma. Due to the extensive nature of the disease involving the orbit and extending intracranially, patient was referred to radiotherapy department for concurrent chemo-radiotherapy. Patient in on regular follow up since last 2 months and have significant improvement in facial swelling. (Fig. 3c)

Fig. 1.

(a) Patient with left facial swelling and proptosis

Fig. 2.

CECT Nose & PNS with Orbit (a) coronal; (b) axial showing homogeneous mass lesion in maxillary sinus and eroding the orbital floor. MRI Nose & PNS with Orbit (c) coronal; (d) axial showing hyperintense mass in maxillary sinus involving left temporal lobe (arrow marked)

Fig. 3.

(a) HPE showing small, uniform round cells with high nucleus to cytoplasmic ratio and warse chromatin (b) IHC showing positivity for CD-99 marker. (c) patient after 2 months of initial diagnosis with ongoing chemotherapy

Discussion

The Ewing’s sarcoma is a highly malignant bone tumor that most commonly affects the long bones of the extremities. Other most common location can be the ribs, pelvis or even the vertebrae. The involvement in the head and neck region is only seen in 1–4% of all cases [4]. The common signs and symptoms include recurrent epistaxis, paresthesia, loosening of teeth or ulceration of the underlying mucosa. The primary Ewing’s sarcoma of the maxilla is even a rarer entity due to its unusual presentation. These sarcoma in the maxillary sinus can cause mass effect leading to bone expansion with erosion of the bone cortex. The case reported here also had the diffuse bony hard swelling in the left cheek area without any history of nasal obstruction, discharge or even nasal bleeding. This unusual presentation can often lead to a diagnostic challenge to the surgeon. Therefore, these tumors are usually locally advanced or even metastatic at the time of diagnosis [6]. The case we reported had the locally advanced disease at the time of presentation. The CECT Nose & PNS is the investigation of choice in a suspected case of sarcoma involving head & neck region. The most common radiological sign in an osseous sarcoma is the periosteal reaction with erosion of the cortical bone. The typical characteristic ‘onion peel’ appearance of Ewing’s sarcoma commonly occurring in long bones is rarely seen in facial bones. MRI can be done in a suspected intracranial or orbital extension. Other diagnostic modalities like PET scan, Technetium-99 m scintigraphy and bone marrow samplings can be done to rule out any distant metastasis [7]. Our case did not have any distant metastasis at presentation. Confirmation of diagnosis is made on the basis of histopathological examination of the tissue biopsy, which can be done either by a core needle biopsy or surgical biopsy. In the current study, punch biopsy was taken under general anesthesia with left endoscopic sinus surgery. Histologically, Ewing’s sarcoma belongs to the small round cell neoplasm with tumor group showing thin, narrow sheets of poorly differentiated cells with high nucleus to cytoplasmic ratio with warse chromatin and scanty cytoplasm. On HPE, the differential diagnosis includes lymphoma, neuroblastoma, rhabdomyosarcoma and primitive neuroectodermal tumor (PNET). Due to the histological similarity of Ewing’s sarcoma with other round cell tumor, diagnosis is often challenging. This diagnostic certainty can be improved using IHC markers specially CD-99. Our case showed positive tumor expression for CD-99 marker and small round cell morphology with other cell markers for neural, skeletal and lymphoid tumors being negative. The Ewing’s sarcoma usually responds well to chemotherapy and radiotherapy. Radical surgery is not recommended as a primary treatment modality [6]. Earlier before the development of chemotherapy, local surgical excision alone was the standard treatment with 5-year survival rate of 10–20%. This low survival rate was due to the subclinical metastatic disease that showed significantly higher relapse rate. The use of adjuvant chemotherapy has now improved the overall survival with a 5-year survival rate up to 70% in many large studies. [3, 8, 9] The current treatment protocol of Ewing’s sarcoma begins with chemotherapy unless contraindicated. Chemotherapy facilitates eradication of micro metastatic disease and helps in effective systemic as well as local tumor control. It can be combined with radiotherapy for better survival outcomes. In the present study, we referred the patient for chemoradiotherapy as the disease was extensively involving the maxillary sinus and was extending intracranially and into left orbit. Patient is currently on neoadjuvant chemotherapy in line with the EURO-EWING 99 Protocol with 6 courses of vincristine, doxorubicin, etoposide and ifosfamide. Simultaneously, patient is also undergoing radiotherapy for better disease control in a planned dose of 52 Gy (Gy) in 29 fractions over 6 weeks. Another reason for choosing this treatment modality over surgery was the age of the patient. Since Ewing’s sarcoma is a radio sensitive tumor, better cosmetic results with good prognosis can be achieved using chemoradiotherapy alone. The patients with Ewing’s sarcoma should be closely followed up with serial MRI screening for 2 years after completion of therapy as recurrence rate of approx. 80% is seen within first 2 years of initial diagnosis [10].

Conclusion

Ewing’s sarcoma is a highly aggressive malignant bone tumor with maxillary sinus being the rare location. The CT and MRI along with HPE and IHC markers warrant early diagnosis and prompt treatment that leads to better survival and prognosis, as unlike Ewing’s sarcoma of long bones, that metastasize early. The combined chemoradiotherapy is now the standard treatment along with close follow up for at least 2 years.

Authors Contribution

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr. Raman Sharma, Dr. Pratik Kumar, Dr. Divya Singh, Dr. Ravi Meher, Dr. Jyoti Kumar. The first draft of the manuscript was written by Dr. Pratik Kumar and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Editing of the manuscript was done by Dr. Raman Sharma, Dr. Pratik Kumar.

Funding

No funding was received for conducting this study.

Declarations

Ethical approval

This study was done in accordance with the ethical standards of the institutional and/or national research committee or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed Consent to participate and publish data

Informed and written consent was taken from the patients before enrolment in the study for their participation in the study and before the submission of the article and a written consent was also obtained for publishing their data in a journal article.

Conflict of Interest

The authors declare “No conflict of interest”.