Extraskeletal Ewing's Sarcoma of parapharyngeal space

1. Introduction 

Ewing's Sarcoma [ES] is an aggressive, round cell, malignant tumour; that occurs primarily in the bone or soft tissue. It can occur in any bone; 50% of reported cases have occurred in the femur or pelvic bones [1]. Primary Ewing's Sarcoma arising in head and neck area is extremely rare and comprise only 1–4% of all cases of Ewing's Sarcoma [2], [3]. Extra skeletal Ewing's Sarcoma [EES] is a rare soft tissue neoplasms, that can develop in the soft tissues at any location. Extraskeletal Ewing's Sarcoma was first reported by Teff et al. in 1969 [4] as paravertebral soft tissue tumours with histological appearance resembling Ewing's Sarcoma. Angervall and Enzinger in 1975 first reported its pathological features [5]; paravertebral region was the most common site of involvement followed by the lower extremity and chest wall. Its occurrence in head and neck as a primary tumour is very unusual and according to Chao et al. [6] in a clinico-pathological study of 118 cases, only five cases were located in head and neck region. Most authors claim better prognosis for ES of head and neck compared to those arising in other locations [7], [8], [9]. The most commonly affected bones in head and neck region are skull, mandible and maxilla. There are reports of localized ES affecting the orbital roof, retropharynx and nasal cavity. An extensive search of the literature revealed only one case of Extraskeletal Ewing's Sarcoma in the parapharyngeal space in a 53-year-old male reported by Ng et al. [10]. We report, the second case of Extraskeletal Ewing's Sarcoma of parapharyngeal space, and first such case in paediatric age group.

2. Case report 

A 6-year-old male child was brought to the ENT department at Safdarjang hospital by his parents with complains of fever and gradually progressive swelling in the oral cavity and neck on the right side since 25 days. He also had inability to open the right eye for 15 days and gradually progressive respiratory difficulty of 2-day duration. There was history of weight loss, diplopia and headache. There was no history of neck trauma, altered sensation, altered smell, nasal obstruction or epistaxis. Personal and family history were unremarkable. Physical examination revealed a large submucosal bulge in the right parapharyngeal region, pushing the right tonsil medially, the soft palate was pushed inferiorly and uvula was oedematous. The posterior pharyngeal wall was normal. The mass was encroaching upon the airway and assessment of larynx was not possible. Cranial nerve examination revealed palsy of III, IV, VI and motor branch of V cranial nerves. Eye examination revealed right sided ptosis with dilated and fixed pupil; and eye ball movements were totally restricted in all gazes. However, Fundus examination was normal. With all these findings a provisional diagnosis of right parapharyngeal mass with cavernous sinus thrombosis with stridor was made; and emergency tracheostomy was done to relieve the respiratory distress.

A diagnostic nasal endoscopy showed a mass in the right nasal cavity blocking the choana, a punch biopsy was taken which was reported as chronic inflammation. CT Scan of head and neck showed a mass, 7.5cm×5.5cm in right parapharyngeal space with extension into nasopharynx which exhibited heterogeneous post-contrast enhancement [Fig. 1]. There was erosion of middle cranial fossa with extension of mass into parasellar region and involvement of ipsilateral cavernous sinus [Fig. 2]. The airway was compromised [Fig. 3]. The Internal Carotid Artery was displaced anterolaterally.

View Large Image Download to PowerPoint

Fig. 1. .

View Large Image Download to PowerPoint

Fig. 2. .

View Large Image Download to PowerPoint

Fig. 3. .

In view of the CT scan findings, the patient was subjected to an incisional biopsy, through a neck incision 2cm below the right mandible, extending from angle of mandible to the midline. Submandibular gland was retracted after ligating facial artery and vein and wedge biopsy was taken from the mass occupying the parapharyngeal space.

Histopathological examination showed features consistent with small round cell tumour. The tumour demonstrated high cellularity composed of small, round uniform cells with oval nuclei and scanty cytoplasm [Fig. 4]. The cytoplasmic organelles were poorly developed. Immunohistochemistry showed immunoreactivity to mic2 protein (CD99) [Fig. 5] and Vimentin and nonreactivity to Cytokeratin, actin, neuron specific enolase and leucocyte common antigen. Thus histological and immunohistochemical findings were confirmatory for Ewing's Sarcoma.

View Large Image Download to PowerPoint

Fig. 4. .

View Large Image Download to PowerPoint

Fig. 5. .

In view of the extensive tumour, the patient was treated with multiagent chemotherapy and concurrent radiotherapy after induction with 2 cycles of Vincristine, Actinomycin D, Cyclophosphamide, and Adriamycin (VACA). The patient received a total of 3935 cGy of external beam radiotherapy with cervical spine shielding. The patient is tumour free with no endoscopic or radiological evidence of tumour recurrence; 10 months post-treatment.

3. Discussion 

EES is a rare malignant tumour of mesenchymal cell origin. There is no sex predilection for this condition prior to adolescence, however, the number of males affected is slightly higher than the number of females after adolescence and may account for the increased incidence in males. Allam et al. [11] has reported a male to female ratio of 2.4:1 in a series of 24 patients. Unlike the osseous form where the median age of occurrence is about 20 years; ESS is diagnosed at an mean age of 16.5 years [11]. However, cases have been reported in patients between 14 months and 63 years of age [5], [12].

Most common site of involvement of EES are paravertebral region, intercostal region, lower extremities and pelvis [5], [12]. EES arising in head and neck is extremely rare and cases have been reported in the nasal cavity, nasopharynx, parotid area, paranasal sinuses, larynx [13], [14], [15], [16]. Only one case has been reported in parapharyngeal space [10]. Around 75% patients present with rapidly growing painless mass, 30% patients exhibiting distant metastasis at the time of diagnosis. Our patient presented with a rapidly growing painless mass in the neck and oral cavity with multiple cranial nerve palsy but did not have any distant metastasis.

Radiologically ES of long bones shows a pattern of bone destruction with aggressive, interrupted periostial new bone formation. In skull it presents as destructive lesion with large associated soft tissue component and no calcification. CT images of ES show heterogeneously enhancing soft tissue mass with bone destruction and no calcification. MR images on T1W1 appear hypointense to isointense and hyperintense on T2W1, reflecting densely packed, small round cells with high nuclear:cytoplasmic ratio [15]. In similarity to above description, the tumour in our patient showed unequal contrast enhancement with irreversible bone destruction and no calcification. ICA displacement anterolaterally and perineural spread along cranial nerves III, IV, V and VI was present.

Ever since its first description by Sir James Ewing there has been remarkable evolution in the concepts regarding its histogenesis and relation with other round cell tumours including primitive neuroectodermal tumours (PNET). Ewing's Sarcoma family of tumours (ESFT) constitutes both ES and EES [17].

Angerwall and Enzinger first reported the pathological features and behaviour of ESS, which are round or oval cell sarcoma of soft tissue and are histologically indistinguishable from ES of bone. Both ES and PNET show varying degree of neuroectodermal differentiation. The term ES has been used for those tumours that lack neuroectodermal differentiation by light microscopy, immunohistochemistry and electron microscopy, whereas the opposite is true for PNET [17]. However there is considerable overlap between PNET and EES. EES is histologically similar to osseous ES, and is often confused with other round cell tumours but recent advances in immunohistochemistry have helped in diagnosis of ESS. Strong immunoreactivity for monoclonal antibody O13 to glycoprotein p30/32 mic2 (CD99) and vimentin is demonstrated in ESFT [6]. Lymphoma, Rhabdomyosarcoma and Neuroblastoma can be excluded by negative staining for Leucocyte common antigen, CD30, actin, Neuron specific enolase and S-100 respectively. Lack of neurosecretory type granules (neurofilaments) seperates classic ES from PNET [15]. Cytogenetic translocation t(11;22) (q24;q11.2-12) is seen in 85–90% cases of ESFT [17]. In our patient immunohistochemistry revealed round cells with high cellularity with scanty cytoplasm and positive reactivity for CD99 and vimentin.

The differential diagnosis of our case were salivary gland tumours, neurogenic tumours, paragangliomas, nasopharyngeal carcinoma, lymphoma and rhabodomyosarcoma which were serially excluded on the basis of radiological, histological and immunohistochemical findings.

This unusual case of parapharyngeal EES demonstrated that immunohistochemistry is a very useful aid in diagnosis of aggressive deep seated tumours of head and neck region, which help in early diagnosis and timely intervention, resulting in decrease morbidity and mortality.

Various therapeutic modalities have been developed and include surgical resection, chemotherapy and radiotherapy. EES follows an aggressive course with high recurrence rate. Distant metastasis is seen most commonly in lungs. Early adequate surgical resection followed by chemotherapy and irradiation offer best chance for long term survival. Distant metastasis, marked tumour necrosis and painful tumour represent poor prognostic signs. Patients aged less than 16 years do better. Due to the extensive spread and involvement of vital structures our patient was treated with concurrent chemoradiation and is doing well 10 months post-treatment.