Analysis Of The Case Study On Ewing’s Sarcoma

Introduction: Ewing’s sarcoma, first described by James Ewing [1] is a small round cell tumor with significant malignant potential. The Ewing's sarcoma are derived from cells of the neural crest and has reciprocal translocation between chromosomes 11 and 22, t (11;22) [2]. Ewing's sarcoma along with Askin tumor and PNET is a part of the Ewing's sarcoma family of tumors (ESFT) [2]. It presents in pediatric age group and there is a slight preponderance of males over females. Long bones and pelvis are the commonest primary site. The occurrence in head and neck region is approximately 2-3% [3].

Case Report: A 17 year old girl presented to us with complaint of painless swelling over left zygomatic region for 3 months which was progressive in nature. No history of facial weakness, fever, diplopia, nasal or ear complaints were present. On examination, there was a 3x2 centimeters (cms) swelling with smooth surface and poorly defined margins over left zygoma, approximately 2 centimeters lateral to lateral canthus, firm in consistency, tender and mobile (Fig. 1). Overlying skin was uninvolved. No scar, sinus or facial weakness was present. Extraocular movements were normal. No other significant clinical finding was present. There was no regional lymphatic spread. Routine blood investigations and Chest skiagram were normal. Sonography of the swelling revealed a heteroechoic lesion of size 1. 5x1. 3 cms along outer margin of zygomatic bone and heteroechoic lesion of size 2x2. 8 cms along inner margin. Contrast enhanced MRI (Fig. 2a) showed enhancing soft tissue mass lesion of size 3. 1x2. 4x4. 1 cms in relation to left zygomatic bone involving both medial and lateral aspects of bone. Lateral aspect of tissue was found infiltrating into subcutaneous region. Mass was infiltrating and involving left masseter muscle in lateral retro maxillary space. Marrow signal intensity of zygomatic bone was altered showing involvement of bone. There was no significant lymphadenopathy.

Contrast enhanced CT scan (Fig. 2b) of face was done which revealed enhancing soft tissue mass lesion of size 3. 1x2. 4x4. 1cms in relation to left zygomatic bone in both medial and lateral aspect with infiltration of subcutaneous tissue by lateral aspect of tumor. Mass was abutting temporalis muscle without any infiltration. Mass was infiltrating and involving left masseter muscle. Subtle permeation and osteopenia of left zygomatic bone was seen suggestive of its involvement. Both CT and MRI were highly suggesting of Ewing’s sarcoma of left zygomatic bone. FNAC of the swelling was done and it was suggestive of small round cell tumor. In view of the possibility of Ewing’s sarcoma and its malignant nature, metastatic workup was advised. CT thorax and abdomen was normal. Bone scan was done in which there was increased osteoblastic activity with increased vascularity seen involving left zygomatic arch. Distal skeletal involvement was not evident. After workup, surgery was planned. An approximately 7 cms curvilinear incision was made extending from lower end of left tragus towards forehead 1 cm above the hairline. A 5x2. 5 cms tumour was found infiltrating masseter muscle, so a cuff of muscle was also resected with tumor (Fig. 3). Zygoma was found to be thinned out and eroded which was removed along with tumor. There was no facial nerve weakness or any other complications post operatively.

Medical Oncologist opinion was sought post surgery and patient was started on chemotherapy (Ifosfamide and Etoposide). Patient has been advised regular follow up. Histopathology was suggestive of poorly differentiated small round cell tumor with suggestion of Ewing’s sarcoma family of tumors (Fig. 4). Other differentials were neuroendocrine carcinoma, lymphoma and poorly differentiated synovial sarcoma. IHC was done for definite diagnosis and CD 99 marker which is seen in more than 90% of cases of Ewing’s sarcoma was found to be positive (Fig. 5a). Tumor cells were also intensely reactive for FLI-1, Pan CK and Vimentin whileTLE1, Desmin, Leukocyte common antigen (LCA), synaptophysin, chromogranin A, WT1 and p63 were negative. Cytogenetic study by Fluoroscence in situ hybridization (FISH) was performed and EWSR1 (22q12) translocation was found in 95% of tumour cells (Fig. 5b). On the basis of clinical features, radiological findings, histopathology report and cytogenetic study, diagnosis of Ewing’s sarcoma of zygoma was made. Discussion: Since its first description by Ewing, origin of Ewing’s sarcoma is under debate. Now a days, it is believed that it is neuroectodermal in origin and derived from cells of the neural crest [1, 2]. It usually involves long bones and pelvis and occasionally ribs also. Only 2-3% of osseous lesion occurs in head and neck region [3].

Mandible is most common site in head and neck region [3]. Primary tumor of zygoma is extremely rare and only 6 cases are reported till date in English literature [4]. Most common age of presentation is between age of 5 and 25 years [5]. Our patient also presented with the age corresponding to this demographic data. There is slight male preponderance noted in this lesion. The characteristic radiological finding associated with Ewing’s sarcoma is “onion skin” appearance which is usually seen in long bones [1]. This finding rarely appears in lesions involving bones of head and neck. Other radiological findings which can be seen are expansion and erosion of bone. CT scan is essential to ascertain extent of disease while MRI can be supplemental to know marrow or soft tissue involvement [1]. Histologically, Ewing’s sarcoma is a highly cellular lesion composed of narrow sheets of small, densely packed and round cells with scanty stroma. Cells show uniformly appearing, small, round-to-oval, hyperchromatic nuclei, and scanty cytoplasm; thus, it is designated as a “small round blue cell tumor” [1].

Immunohistochemical staining with MIC-2(CD-99) is required for confirmation of diagnosis. The MIC2 gene is expressed in more than 90% of Ewing's sarcoma [1]. It is also positive for vimentin while it is negative for desmin and myogenin. Other differentials for small round cell tumor are lymphoma, rhabdomyosarcoma and neuroblastoma. These are morphologically similar on histology as all of these are small round blue cell tumor and differentiated on Immunohistochemistry only. The closest differential of Ewing's sarcoma is primitive neuroectodermal tumor (PNET) as they belong to same family. Histologically, there are differences between these two tumors. PNET tends to represent the well differentiated end of the tumor spectrum, Ewing's sarcoma being at the opposite extreme of the spectrum [6]. Cytogenetic study for EWSR1-FLi1 fusion may be required for confirmation. This fusion is seen in more than 90% of cases [2].

The treatment is based on presentation i. e. localized or metastatic or recurrent and site. Surgical excision is the modality of choice followed by postoperative chemotherapy. Radiotherapy should be reserved for unresectable or residual disease. Prognosis of this tumor also depends on site and presence of metastasis. Most common site for metastasis is lungs. Other sites can be bones or lymph nodes. Survival rates in head and neck Ewing’s sarcoma are much better than that of other sites. Conclusion: Head and neck region swelling is quite common in day to day practice but there are some lesions which lead to diagnostic uncertainties. Ewing’s sarcoma of zygoma is extremely rare and should be kept as a differential diagnosis in head and neck region swelling particularly in young age group with destruction or erosion of bones. Immunohistochemistry is essential for obtaining a diagnosis. It is essential to keep these patients in regular follow up as a part of successful management.