INTRODUCTION

Primary intracranial sarcomas are extremely rare tumours and only a single case has been reported recently. 43 Ewing's Sarcoma arising primarily in the skull is a less frequent type that neurosurgeons come across. This report is of a case of Primary Intracranial Ewing's Sarcoma in an adult presenting as an acute neurosurgical emergency. The related literature is reviewed.

CASE REPORT

A 25 years old male was transferred from a local Hospital to neurosurgical services of Dammam Central Hospital, Dammam, Saudi Arabia, in 1992, with sudden onset of unconsciousness and left hemiplegia of 4 hours duration. He had intermittent headaches for 4 days. There was no history of any illness, epilepsy, and trauma prior to this presentation. Examination revealed a Glasgow Coma Score of 8 (E-2, V-1, M-5), bilateral papilledema, right pupil dilated with no reaction to light, left pupil normal in size and reacting to light, left hemiplegia with extensor plantar and no nuchal rigidity. Vital signs were normal with respiratory rate of 20/min, pulse rate of 80/min and blood pressure 110/80 mm Hg. General physical and systemic examination was unremarkable.

	Figure 1 — Lateral skull roentgenogram showing lytic lesion in the right frontoparietal bone (parasaggital)		Figure 4 — Photomicrograph showing solidly packed small round tumour cells with inconspicuous cytoplasm and indented nuclei (haematoxylin and eosin, x 40). Special stains showed glycogen, supporting diagnosis of Ewing's Sarcoma.

	Figure 2 —Axial post contrast CT scan showing irregularly enhancing mass in the right frontoparietal lobe (8.5 x 7.5cm).		Figure 3 — Axial CT scan (bone window setting) showing erosion of the inner table in the right frontoparietal bone.

Plain x-ray skull revealed osteolytic area in the right fronto-parietal bone (Fig. 1). An emergency computed tomography (CT) scan of the brain showed a large enhancing space occupying lesion in the right fronto-parietal lobe with marked shift and surrounding edema (Fig. 2). Bone window settings showed erosion of the inner table at the site of lesion (Fig. 3). Patient underwent emergency right fronto-parietal craniotomy. The inner surface of the bone measuring 6x4 cm was found eroded and hence discarded. The dura was involved by a large intradural pinkish white mass, vascular and soft to firm in consistency. This extracerebral tumour was removed enmasse along with the dura after coagulating feeding vessels. A duraplasty was done using pericranial graft. Post operatively patient did well and had complete neurological recovery. Histological examination of the tumour revealed it to be Ewing's Sarcoma (Fig. 4), and both the dura and bone were infiltrated by tumour cells. Radionuclide bone scans; chest radiographs, CT abdomen, chest and pelvis revealed no evidence of any other lesion. Patient received post operative radiotherapy, 4000 cGy to whole brain and a boost to the right fronto-parietal region of 1500 cGy. Total dose received- 5600 cGy. Patient received chemotherapy after the radiation therapy in the form of Vincristin (1.5 mg/ sq. Mt IN. weekly, alt. Week), Actinomycin D (2 mg /sq. Mt I. V. once a month x 6 months), Cyclophosphamide (300 mg / sq. Mt I.V. weekly, every alternate week x 6) and Adriamycin (30 mg / sq. Mt I.V. daily x 2 days every month x 6). Patient tolerated the treatment well. He underwent cranioplasty three months later. He is being followed regularly and to date is free of any recurrence.

DISCUSSION

A variety of primary intracranial sarcomas are known. These are extremely rare tumours and constitute < 1% of all brain tumours. 27,43 Paulus et al (43) recently screened the relative frequency of currently accepted sarcoma types and encountered only 19 cases among a total of 2500 biopsy proven brain tumours. They encountered only one case of Primary Ewing's Sarcoma arising in the skull.

James Ewing first described Ewing's Sarcoma in 1921. (15) This is an uncommon malignant bone neoplasm representing about 10% of all malignant bone tumours. (35) It affects children and young adults. Seventy-five percent cases occur under 20 years of age, peak incidence is between 5 and 13 years. 12,25,54 Most of the primary tumours arise in long bones (47%), pelvis (19%) and ribs (12%), (1,I2,16) The tumour affects jaws more frequently than the skull and a combined incidence is given as 9%. 16 Although primary skull involvement is considered to be up to 4%, (5,12,16) there have been mostly single case reports. Metastasis occurs in 75-80% of the cases during the first two years (1) and 14-28% had evident metastasis at diagnosis. (5,16,64) The risk of developing isolated CNS metastasis is greatest in the first two years after diagnosis and is approximately 10%. 59

Histologically Ewing's Sarcoma is a highly anaplastic tumour with solidly packed small round cell. (16) Presence of glycogen is used as a positive marker of Ewing's Sarcoma. (16,54) Histological and immunohistochemical features correspond to those of extracranial sarcoma. (43) Primary and secondary intracranial sarcomas cannot be histologically separated; hence a thorough clinical examination and follow-up are mandatory. (43) Soft tissue mass of Ewing's Sarcoma does not ossify in contrast to the soft tissue mass of osteogenic and chondrogenic sarcomas. (16) It is postulated to be a myelogenic tumour of multifocal origin with a manner of spread similar to plasma cell myeloma. l The differential diagnosis of an intracranial round cell tumour is primitive neuroectodermal tumour (neuroblastoma),lymphoma, rhabdomyosarcoma and Ewing's Sarcoma. (24,54) Light microscopic, ultrastructural and immunohistochemical features (24,54) can differentiate these tumours. However owing to its rarity, it continues to present difficulty to the histopathologists. Fine needle aspiration has also been utilised for diagnosing Ewing's Sarcoma. Clusters of monomorphic tumour cells with round vesicular nuclei and ill defined delicately vacuolated cytoplasm, many dissociated cells presenting as naked nuclei and glycogen demonstration in cytoplasm in most of the tumor cells confirm cytological features of Ewing's Sarcoma. (26)

Many reports mention central nervous system (CNS) involvement by Ewing's Sarcoma, mostly referable to spine and only a minority had affection of skull. (10,12,32,35,47,53,63) Even though primary skull Ewing's Sarcoma is considered to be very rare and most authors cite review of few case reports, 1,29,37,54,57,65 literature search revealed 33 case reports and another 18 cases involving skull Vohra VG (63) while describing roentgenographic manifestations in 156 cases of Ewing's Sarcoma recorded 8 involving the skull bones. Dahlin D, (12) in his report on 6,221 bone tumors, found only 4 cases involving the skull out of 299 cases of Ewing's Sarcoma. Coley B, (l0) indicated 3 instances of primary skull involvement of the skull out of 149 cases and Pritchard DJ (47) reported 3 instances among 234 cases. Of the 33 cases 15 originated in skull base; temporal bone in 7 cases; (4,8,16,23,30,54,65) mastoid in 2 cases; (21,69) and one case each of orbital roof, (10) sphenoid, (40) ethmoid, (24) floor of middle fossa, (29) zygoma (46) and unspecified (66). Tumour originated in the skull vault in 18 cases (excluding this case) - frontal in 5 cases; (2,32,37,39,43) fronto-parietal in 4 cases; (25,37,49,67) parietal in 2 cases; (19,22) temporo-parietal in 2 cases; (26,31) occipital in 2 cases; (17,68) and one case each of parieto-occipital, (57) squamous temporal, (13) unspecified (19). In 25 cases sex pattern was available and there were 14 females and 11 males. Age distribution in 27 cases revealed - one new born female, 2 preschool children, 13 children, 6 adolescents and 5 adults. Our case was 25 years old male and tumour was located in the right fronto-parietal region.

Pain and swelling are the most common symptoms and signs if the tumour is located peripherally. (1) With the CNS involvement, headache is most common complaint and papilledema the most common sign. (35) More commonly neurological symptoms result from compression or direct invasion by extradural tumour involving skull bones. l Several cases of primary skull Ewing's Sarcoma reported had visible external swelling.( l.17,24,26,32,37,54) Presentation by neurological symptoms alone in cases involving calvarium was reported in few cases. (19.37,57) None of the cases reported presented as acute neurosurgical emergency except the case of Tournet et a1 (57) although reported as acute surgical emergency had only headache, diplopia and papilledema (the most common features of CNS involvement). Our case is unique in that it presented as acute neurosurgical emergency with sudden onset unconsciousness, signs of tentorial herniation and hemiplegia.

There were only three instances mentioning intradural extension of the tumour, (22,37)-Case 1. 40 In our case tumour was basically intradural and grossly appeared as if infiltrating dura and inner table of the skull. There were 7 instances where dura was involved by extradural tumour or adherent to it (1,22,24,32,37), Case 2 (43,54,57) In cases of Mishra et a1, (37) intracerebral hematoma was noted in Case 1 and carpet like involvement of dura in Case 2.

Plain skull x-rays in these cases revealed lytic bone lesion, (1,32,54,68) normal in the case of Tournet et also but CT showed erosion of the inner table. CT scans appearance of the soft tissue mass is usually an isodence to hyperdence mass, which enhances regularly or irregularly with contrast. 1,24,32,37,57,68 Magnetic resonance imaging (MRI) has been useful for precise delineation of the different tumour components, such as extent of bone and dural involvement. (55) Radionuclide bone scanning is effective in determining primary lesion, metastasis and follow up; and Ewing's Sarcoma lesion may show uptake on radionuclide angiography. 16 Chest radiographs and CT scans are most effective in showing pulmonary metastasis. Cerebral angiography: usually tumour receives main blood supply from vessels normally supplying scalp and vault. (32,54)

A number of reports of secondary Ewing's sarcoma affecting skull and brain are also reviewed and encountered in 31 cases. (3,6,7,9,11,20,28,33, 34,36,38,41,42,44,50,53,55,56,58,60,61) 1n 25 cases location of the metastasis was available - in 11 cases it was intraparenchymal, (6,7,36,38,41,51,53) in 12 cases it affected skull - Skull base (20,50,61) Vault (9,42,44,55,56). In one case there was initial skull metastasis which later developed parenchyma) metastasis independent of the previous one. (33)_ One case had multiple metastasis involving scalp, skull and brain. 61 The occurrence of isolated CNS involvement was not prevented by use of radiotherapy and intrathecal methotrexate. (59)

The results of treatment had been poor initially and 5 year survival in the range of 5-16% until 1970. (1,12,24,27,32,47,53) The prognosis has improved in the last two decades and most series report 2-5 years disease free survival of 50-80%, when adjuvant chemotherapy is used irrespective of surgery verses radiotherapy. (1,14,18,24,48,54) Ewing's Sarcoma of the calvarium generally grants a favourable prognosis following surgery and/or irradiation and chemotherapy. Those at the skull base may be difficult to eradicate. (16,22,54) Seventy -five percent were tumour free 6 months to 7 years post surgery and reminder survived 21 months average. (22) Our case had total removal of the tumour including dura and bone followed by radiotherapy and chemotherapy. Patient is about 6 years post surgery and to date free of any recurrence. Suit HD, reported local recurrence after radiation therapy alone to be 27-38% 1 Four-drug combination VACA (vincristin, actinomycin D, cyclophosamide and adriamycin) can be considered as gold standard chemotherapy regime for Ewing's Sarcoma. 14 Concerning local therapy adequate radiotherapy plays a major role and achieves the similar survival rates as radical surgery. An objective response to radiotherapy and chemotherapy was observed in the case of Alvarez et al, (l) when the specimen failed to reveal presence of any active tumour after second surgery. However, radiotherapy as a sole local treatment is indicated in inoperable lesions of spine, skull, sacrum and in small good responding tumours. (14) High-risk patients should receive combined radiotherapy-surgical treatment, preferably pre-operative irradiation to the lesion. (14) Preliminary study by Uhl V (62) has shown that heavy charged particle irradiation can be effectively used to control bone sarcoma.

Local recurrence in the skull was noted in one case, 2.5 years after first operation and serial bone scanning helped in the detection of subclinical recurrence. (67) So far there have been no report of metastasis to other sites from a primary tumour arising in the skull.

Certain clinical and laboratory prognostic factors seem to indicate good outcome: (a) duration of symptoms longer than 6 months, (b) absence of fever or systemic symptoms, (c) absence of metastasis at diagnosis, (d) a peripheral location of tumour, (e) Laboratory investigations showing: initial LDH levels-170 i.u. / Litre or less, WBC 7000 or less, lymphocyte count of less than 2000, a platelet counts below 400,000. (45)

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