|Year : 2012 | Volume
| Issue : 4 | Page : 636-638
Skull-base Ewing sarcoma with multifocal extracranial metastases
Sumit Thakar1, Sunil Furtado1, Nandita Ghosal2, Jethwani Dilip3, Anita Mahadevan3, Alangar Hegde1
1 Department of Neurosurgery, Sri Sathya Sai Institute of Higher Medical Sciences, EPIP Area, Whitefield, India
2 Department of Neuropathology, Sri Sathya Sai Institute of Higher Medical Sciences, EPIP Area, Whitefield, India
3 Department of Neuropathology, National Institute of Mental Health and Neuro Sciences, Bangalore, Karnataka, India
|Date of Web Publication||29-Jan-2013|
Department of Neurosurgery, SSSIHMS, EPIP Area, Whitefield, Bangalore - 560066
Source of Support: None, Conflict of Interest: None
Intracranial occurrence of Ewing sarcoma (ES) is unusual, with a skull-base location being anecdotal. We report a 29-year-old man who presented with rapidly progressive ophthalmoplegia, and was found to be harboring an infiltrative lesion involving the sphenoid sinus, sella, and clivus. He underwent trans-sphenoidal decompression of the lesion which was histologically suggestive of ES. He developed paraparesis 2 weeks after commencing adjuvant therapy. Imaging revealed two thoracic extradural lesions and florid vertebral and pulmonary metastases. This is the first report in indexed literature of a primary intracranial ES on the skull-base with disseminated extracranial disease.
Keywords: Clivus, Ewing sarcoma, primitive peripheral neuroectodermal tumor, skull base, sphenoid sinus
|How to cite this article:|
Thakar S, Furtado S, Ghosal N, Dilip J, Mahadevan A, Hegde A. Skull-base Ewing sarcoma with multifocal extracranial metastases. J Can Res Ther 2012;8:636-8
| > Introduction|| |
A relatively rare malignancy, the Ewing sarcoma (ES), is the second most common bone tumor in the pediatric age group. Intracranial presentation of ES is rare, with a reported incidence of 1-6% of all cases.  The cranial lesions commonly involve the calvarium, , while the skull-base remains an infrequent site of primary occurrence. ,, We report an unusual case of an ES in the sphenoid sinus, sella, and clivus with florid systemic metastases.
| > Case Report|| |
A 29-year-old man presented with history of intermittent headache and vomiting and progressive restriction of movements of the right eye since 3 weeks. His neurological deficits included right-sided complete III rd , IV th , and VI th nerve palsies and decreased sensations in the right V1 and V2 divisions of the trigeminal nerve. CT brain with bone windows demonstrated a destructive lesion in the sphenoid sinus and clivus [Figure 1]a and b. MRI brain [Figure 2]a-c revealed that the lesion had contiguously involved the sphenoid sinus and clivus and also had a component in the sellar and parasellar regions. It was hypointense on T1-weighted images (WI) and hyperintense on T2 WIs and homogenously enhanced with contrast. Hormonal evaluation revealed hypothyroidism and hypocortisolemia for which appropriate replacements were instituted. Decompression of the lesion was undertaken via a simple, microscopic, transnasal- transphenoidal approach. In view of the frozen section report of a malignant round cell tumor and the infiltrative nature of the lesion, decompression was restricted to limited debulking. Histological examination showed sheets of small, round cells organized into lobules by variably hyalinized and vascular septae [Figure 3]a. The cells had clear cytoplasm, reflecting glycogen content. The nuclei were vesicular and the nucleoli indistinct [Figure 3]b. The MIB-1 labeling index of the tumor was 35%. On immuno-histochemistry, the tumor cells were immunopositive for CD99 [Figure 3]c, neuron-specific enolase, cytokeratin AE1/AE3 and synaptophysin, and negative for CD45, CD20, neurofilament, S-100 protein, chromogranin, carcinoembryonic antigen, and calcitonin. These findings were consistent with the diagnosis of Ewing's sarcoma.
|Figure 1: Bone windows of CT brain showing evidence of a destructive lesion involving the sphenoid sinus (a) and clivus (b)|
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|Figure 2: Axial section of a T1 weighted, gadolinium-enhanced MRI of the brain showing a contrast enhancing lesion in the sphenoid sinus, sella, and clivus (a); coronal section of the T2-weighted image (WI) showing bilateral encasement of the cavernous carotid artery (b); sagittal section of a T1WI showing carpeting of the lesion onto the clivus (c)|
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|Figure 3: Microphotographs showing a densely cellular tumor in tight cohesive nests deep to the submucosa (a, arrow, mucosa) of the sphenoid sinus. Tumor cells with vesicular, large nuclei, and clear cytoplasm seen arranged in lobular clusters; (b) demonstration of strong membrane expression for CD99 (c). [a: HE×80, b: HE×280, c: Immunoperoxidase, CD99×400]|
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A whole-body CT was negative for any other osseous or extra-osseous lesions. A bone scan [Figure 4] showed increased uptake in the skull base in the region of the residual tumor and no evidence of hot spots elsewhere, confirming the primary nature of the skull-base lesion. Adjuvant radiation therapy (RT) was commenced for the residual tumor with a plan of adding on a four-drug chemotherapy regimen (vincristine, adriamycin, cyclophosphamide, and actinomycin-D) post-RT. Two weeks after the initiation of RT, he developed spastic paraparesis and progressive dyspnea. MRI spine showed multiple enhancing lesions throughout the spine [Figure 5]a-c with two extradural lesions in the mid-thoracic spine [Figure 5]b. CT thorax showed two small nodules in the right lung and moderate to gross pleural effusion bilaterally [Figure 6]. Pleural tap revealed a hemorrhagic exudative fluid with malignant round cells on cytology. His clinical condition rapidly deteriorated and he succumbed to his illness a week later.
|Figure 4: Bone scan images prior to starting adjuvant therapy demonstrating increased uptake in the skull base corresponding to the residual tumor. Note the absence of increased uptake in any other area|
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|Figure 5: Sagittal sections of a contrast MRI of the spine showing multiple enhancing lesions in the vertebral bodies in cervical (a); thoracic (b); lumbosacral (c) regions. Extradural lesions noted from T7 to T9 levels in (b)|
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|Figure 6: Axial section of a CT of the thorax showing bilateral pleural effusion|
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| > Discussion|| |
The Ewing family of tumors, consisting of Ewing sarcoma (ES) and its biological counterpart, the peripheral primitive neuroectoderm tumor (pPNET), constitute an uncommon malignancy of childhood and adolescence with a predilection for soft tissue and bones of the trunk and extremities. It has preponderance for males in the first and second decades of life, with a peak incidence between 5 and 13 years.  When situated in its typical locations in the skull vault, the ES commonly presents with headache related to raised intracranial pressure or with a classical, osteomyelitis-like picture. Its occurrence in the skull-base, usually a metastatic manifestation, presents with varying involvement of cranial nerves dependant on the location. , Extracranial metastasis from a primary ES in the cranium is exceptional,  while cranial metastasis from extracranial ES is common.  While systemic spread to the lungs is common in ES, the occurrence of a malignant pleural effusion, like in our case, is only rarely reported in ES. 
Radiologically, a host of pathologies may be included in the list of differential diagnoses while evaluating a skull base lesion like ours. Malignant pathologies like skull base metastasis, nasopharyngeal or sphenoid sinus carcinoma, lymphoma, and plasmacytoma are known to display nonspecific intensities on MRI, and may present with disseminated metastases. The chordoma, a locally infiltrative neoplasm, typically expands the clivus and demonstrates foci of sequestered bone or calcification, iso- to hypo-intensity on T1 weighted images (WIs), heterogenous hyperintensity on T2 WIs and variable contrast enhancement. Radiologically indistinct from the chordoma, the chondrosarcoma tends to occur laterally, often centered on the petroclival suture. The pituitary macrodenoma, typically centerd in an enlarged sella, and a suprasellar meningioma distinguished by homogenous enhancement with a dural tail and an epicentre in the suprasellar cistern, are among the common benign pathological differentials.
Multimodal approaches, including surgery, radiotherapy, and intensive multiagent-chemotherapy, have remarkably improved survival in patients with localized ES. By contrast, the prognosis of patients with disseminated ES remains poor.  The Ki-67/ MIB-1 index, commonly between 7-10% in ES, has been linked with tumor progression. In our case, a MIB-1 index of 35% well predicted the ensuing aggressive clinical course. A type 1 EWS-FLI1 fusion transcript has been associated with a favorable prognosis, while the insulin-like growth factor 1 (IGF-1) and a nontype 1 EWS-FLI1 fusion transcript have been linked to aggressive clinical phenotypes in ES.  Several analyses have shown age, tumor site, tumor volume, responsiveness to chemotherapy, and sites of metastases to be of major prognostic value, with the most relevant risk factor being primary dissemination at the time of diagnosis.  A recent international, multicenter, randomized, prospective trial, the European Ewing Tumor Working Initiative of National Groups (EURO-E.W.I.N.G. 99), has reported that local treatment of both the primary tumor and extrapulmonary metastases significantly improves prognosis.  Ensuring compatibility of high-dose chemotherapy and local treatment to achieve optimal results, however, remains a priority task for the oncologist.
| > Conclusion|| |
A primary skull-base Ewing sarcoma, a rare entity, should be included in the oncologist's diagnostic armamentarium while managing an invasive tumor of the sphenoid sinus, sella, cavernous sinus or clivus.
| > References|| |
|1.||Li WY, Brock P, Saunders DE. Imaging characteristics of primary cranial Ewing sarcoma. Pediatr Radiol 2005;35:612-8. |
|2.||Desai KI, Nadkarni TD, Goel A, Muzumdar DP, Naresh KN, Nair CN. Primary Ewing's sarcoma of the cranium. Neurosurgery 2000;46:62-8. |
|3.||Steinbok P, Flodmark O, Norman MG, Chan KW, Fryer CJ. Primary Ewing's sarcoma of the base of the skull. Neurosurgery 1986;19:104-7. |
|4.||Kadar AA, Hearst MJ, Collins MH, Mangano FT, Samy RN. Ewing's Sarcoma of the petrous temporal bone: Case report and literature review. Skull Base 2010;20:213-7. |
|5.||Balasubramaniam S, Nadkarni T, Menon R, Goel A, Rajashekaran P. Primary Ewing's sarcoma of the petroclival bone. J Clin Neurosci 2008;15:712-4. |
|6.||Tanboon J, Sitthinamsuwan B, Paruang T, Marrano P, Thorner PS. Primary intracranial Ewing sarcoma with an unusually aggressive course: A case report and review of the literature. Neuropathology 2012;32:293-300. |
|7.||Ozge C, Calikoglu M, Cinel L, Apaydin FD, Ozgür ES. Massive pleural effusion in an 18-year-old girl with Ewing sarcoma. Can Respir J 2004;11:363-5. |
|8.||Ladenstein R, Lasset C, Pinkerton R, Zucker JM, Peters C, Burdach S, et al. Impact of megatherapy in children with high-risk Ewing's tumours in complete remission: A report from the EBMT Solid Tumour Registry. Bone Marrow Transplant 1995;15:697-705. |
|9.||de Alava E, Panizo A, Antonescu CR, Huvos AG, Pardo-Mindán FJ, Barr FG, et al. Association of EWS-FLI1 type 1 fusion with lower proliferative rate in Ewing's sarcoma. Am J Pathol 2000;156:849-55. |
|10.||Haeusler J, Ranft A, Boelling T, Gosheger G, Braun-Munzinger G, Vieth V, et al. The value of local treatment in patients with primary, disseminated, multifocal Ewing sarcoma (PDMES). Cancer 2010;116:443-50. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]