Ewing’s Sarcoma of the Sinonasal Tract: A Report of Two Challenging Cases

Abstract

Ewing’s sarcoma (ES) is a malignant small round cell tumor that belongs to the primitive neuroectodermal tumor class. ES generally arises in the long bones of the extremities (skeletal form) and less frequently in the soft tissue of the trunk and extremities (extra-skeletal form). Sinonasal localization of ES is an extremely rare event. About 80% of the patients are less than 20 years old with the highest incidence in the second decade of life. The combination of histopathological examination and ancillary methods (such as immunohistochemistry and molecular genetics) is extremely important to establish the diagnosis of ES. The most effective treatment plan for ES includes a multidisciplinary approach with surgery, radiotherapy and chemotherapy. This is a report of two challenging cases of sinonasal ES in two different age groups. The first case is a 13-years old female patient who presented with right nasal obstruction, anosmia, intermittent epistaxis and hearing loss. The second case is a 24-years old male patient who presented with a history of right nasal obstruction, right eye pain and periorbital edema. We present these cases due to the rarity of the disease and the difficulty of diagnosis.

Introduction

Ewing’s sarcoma (ES) is a highly malignant and rare tumor which belongs to the primitive neuroectodermal tumor (PNET) class [1, 2]. This class can be subdivided into: neuroblastoma, central nervous system PNET and peripheral primitive neuroectodermal tumour (pPNET) which include ES [2]. The World Health Organization (WHO) classified ES and pPNET as a single identity under the name ES/pPNET [3].

Skeletal and extra-skeletal forms are known entities of ES [1, 4]. The skeletal form is more common and typically occurs in the long bones of the extremities [1, 4]. The extra-skeletal form occurs in the soft tissues of the lower extremities, paravertebral tissues, chest wall, retroperitoneum and rarely in the head and neck region [1, 4]. Sinonasal localization of ES is an extremely rare event [3]. ES is more common in the children and adolescents with a slight male gender predominance [3, 5, 6].

First Case (Pediatric)

On March, 2010, a 13-years old female patient referred to the ENT clinic complaining of right sided nasal obstruction, anosmia, intermittent epistaxis, snoring and hearing loss for 7-months duration. There was no history of trauma, anorexia or weight loss.

Clinical examination revealed a right sided nasal mass pushing the septum to the left side and extending to the nasopharynx. On throat examination, the soft palate was pushed down by the nasopharyngeal mass. Otoscopy showed dullness and retraction of tympanic membrane bilaterally. Cranial nerves examination was normal. No cervical lymph nodes were palpable. The result of hematological and biochemical investigations were within normal limits.

On radiological evaluation, CT scan revealed an opacification of the right nasal cavity, maxillary, ethmoidal, sphenoid and frontal sinuses with bone remodeling of the septum to the left side (Fig. 1). Subsequently, the patient underwent endoscopic excision of the tumor that was occupying the right nose, maxillary, ethmoid sinuses and nasopharynx. The posterior ethmoid, sphenoid and frontal sinuses were free of the disease. Histopathological analysis showed a small blue cell tumor (Fig. 2). Final diagnosis of sinonasal ES was established based on histopathology and immunohistochemistry that showed positive staining for CD99 marker (Fig. 3). The patient was treated with surgery, radiotherapy and chemotherapy. After a follow-up of 5 years, the patient remains recurrence-free with excellent functional status and quality of life.

Fig. 1.

Computed tomography (CT) scan showing a mass causing an opacification of the right nasal cavity, ethmoid and maxillary sinuses

Fig. 2.

Microscopic analysis showing sheets of small round blue cells

Fig. 3.

Immunohistochemistry of tumour sample showing CD99 positivity

Second Case (Adult)

A 24-years old male patient who presented with a history of right nasal obstruction, right eye pain, lower eyelid swelling and orbital swelling. Endoscopic examination revealed an obstructive mass occupying the right nasal cavity (Fig. 4). Cranial nerves were intact. No cervical lymph nodes were palpable. The result of hematological and biochemical investigations were within normal limits.

Fig. 4.

Nasal endoscopy image showing a soft tissue mass arising from the right lateral nasal wall

On radiological evaluation, CT scan with contrast of the paranasal sinuses (PNS) revealed a mass involving the right ethmoid sinus with medial wall and orbital floor extension (Fig. 5). The subsequent magnetic resonance imaging (MRI) revealed an infiltrative soft tissue mass occupying the right ethmoid sinus, eroding inferior-medial orbital wall and extending to the extraconal space (Fig. 6). Positron emission tomography (PET) scan demonstrated an ill defined 4.5 × 4.2 cm mass lesion in the right nasal cavity and ethmoid sinus extending to the right medial orbital floor (Fig. 7). The scan did not reveal any associated lymphadenopathies.

Fig. 5.

Coronal CT scan with contrast of PNS showing an enhancing soft tissue lesion in the right ethmoid, eroding the medial and inferior orbital walls

Fig. 6.

MRI showing an enhancing soft tissue mass in the ethmoid sinus, eroding inferio-medial orbital wall

Fig. 7.

PET scan showing an ill-defined 4.5 × 4.2 cm mass lesion in the right nasal cavity, maxillary and ethmoid sinuses extending to the right medial orbital floor

Histological analysis of a biopsy from the mass revealed a small rounded blue cell tumor suggestive of ES/pPNET. Immunohistochemistry showed the neoplastic cells are positive for CD99, S-100 protein and vimentin. However, neuron specific enolase (NSE), smooth muscle actin (SMA), desmin, myogenin, CD45, synaptophysin and pan-cytokeratin were all negative. KI-67 index was 30–40%.

Subsequently, molecular study using fluorescence in situ hybridization (FISH) had shown rearrangement of EWSR1 gene in 100% of the analyzes nuclei that confirm the diagnosis of Ewing’s sarcoma. The patient underwent endoscopic excision of the tumor followed by chemotherapy and radiotherapy treatment. MRI 6-months post treatment showed complete resolution of the disease (Fig. 8). The patient remains free of the disease for 5-years follow-up and maintains a very good quality of life.

Fig. 8.

MRI post treatment showing total resolution of the tumor

Discussion

ES is a rare and aggressive tumor that was first described by James Ewing in 1921 [4]. It is a small, round cell tumor that commonly occurs in early childhood and adolescence [5, 7]. About 80% of the patients are younger than 20 years old with the highest incidence in the second decade of life [4, 5, 8]. While ES accounts for 4% to 6% of all primary bone tumors, head and neck are involved in only 1% to 4% of all ES [1, 6, 8]. Furthermore, ES in the nasal cavity and PNS are extremely rare [1, 6].

Most common clinical manifestations of sinonasal ES are enlarging mass, nasal obstruction, rhinorrhea and epistaxis [2, 3]. Nonetheless, 15% to 30% of the patients are presented with metastasis [2]. The lungs and bones are the most common sites of distant metastasis [2].

Microscopically, ES are composed of uniform small round cells with round nuclei containing fine chromatin, scanty clear or eosinophilic cytoplasm and PAS-positive intracytoplasmic glycogen granules [2, 4].

A variety of small round cell tumors can arise from the sinonasal tract [4, 8]. These tumors which mimic sinonasal ES include rhabdomyosarcoma, lymphoma, poorly-differentiated carcinomas, melanoma and olfactory neuroblastoma [2, 4, 8]. Although diagnosing sinonasal ES is challenging, it is feasible using histopathological examination and ancillary methods like immunohistochemistry and molecular genetics [3, 4, 7]. The immunohistochemical profile usually shows CD99 and Fli-1 positivity [1, 4]. In order to reach a definitive diagnosis of ES, molecular analysis is needed to detect EWS/FLI-1 fusion that result in a t(11:22)(q24:q12) translocation [1]. In the present cases, immunohistochemistry revealed CD99 positivity in the first case and CD99, S-100 protein and vimentin in the second case.

The most important prognostic factors are the anatomic site of the tumor, the presence of distant metastasis at presentation, and the age of the patient [4, 5]. Yeshvanth stated that patients younger than 15 years old and patients with axial and sinonasal tract diseases have a better outcome [4]. A good prognosis can be expected if the disease has not metastasized [4, 5]. Metastatic disease at time of presentation is associated with 22% 5-year survival compared to 55% in patients with local disease [4, 5]. With modern treatment modalities, the survival rate in patients without metastatic disease has improved to 86% [8, 9]. The most effective treatment plan for ES includes a multidisciplinary approach with surgery followed by adjuvant radiotherapy and chemotherapy [3, 4, 8].

In our cases, both patients were treated with surgery followed by chemotherapy and radiotherapy. They remained free of the disease for 5-years follow-up and maintained a very good quality of life.

Conclusion

ES in the sinonasal tract is an extremely rare event, hence the early detection of the disease is difficult. However, the accurate diagnosis depends on physician awareness, histopathological examination and ancillary methods like immunohistochemistry and molecular genetics. In the present cases, diagnosis of sinonasal ES was established based on histopathology and immunohistochemistry. In addition, cytogenetic analysis showed rearrangement of EWSR1 gene that confirm the diagnosis in the second patient. Accordingly, both patients received combination treatment regimen with surgery, chemotherapy, and radiation therapy. They remain recurrence-free and maintain a good quality of life.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Informed Consent

Informed consent was obtained from all individual participants included in the study.