Primary Ewing's Sarcoma of Cranium in a Pediatric Patient.

Ewing's sarcoma primarily involving the skull is an unusual occurrence (1% of all Ewing's sarcoma cases) with very few reported cases in the published literature. The challenge in such cases is to establish a definitive diagnosis before starting the multidisciplinary treatment approach. We report such a rare case in a 13-year-old boy who is being treated at our institute with an intention of adding to the limited information we currently have on diagnosis, management, and the outcome of such cases.

INTRODUCTION

Ewing's sarcoma is the second most common bone tumor in pediatric age group and makes up about 10% of all primary malignant bone tumor in children.[1] The most common age of presentation is first and the second decades of life. This is considered a member of the primitive neuroectodermal tumor group described by the World Health Organization (WHO).[2] The most common bones involved by this group of malignancy are the long bones and the pelvis. Primary Ewing's sarcoma involving the cranial bones is extremely rare. Cranial Ewing's sarcoma makes up 1% of the Ewing sarcoma cases with only 71 cases reported till date in published literature.[1] We report such a rare case of Ewing's sarcoma in a 9-year-old child.

CASE REPORT

A 13-year-old boy presented to the outpatient department of our institute on January 17, 2017 with a painless lump over the left side of the head. He noticed it 2 years ago when it was just the size of a marble. It started growing 3–4 month ago and reached the size of a lemon. There was no associated pain, tenderness, headache, convulsions, vomiting, or fever. Magnetic resonance imaging brain was suggestive of a well-defined space-occupying lesion of left frontal bone [Figure 1]. The lesion was 62 mm × 5 mm × 65 mm in size and heterogeneously hyperintense on T2-weighted images and hypointense on T1-weighted images with internal areas of calcification which showed blooming on gradient-echo images. It had a broad base toward dura with well-defined cerebrospinal fluid cleft between the lesion and adjacent left frontal lobe of brain parenchyma and buckling of adjacent gray-white matter junction which indicated toward the extraaxial origin of the lesion. There was the widening of the diploic space of left frontal bone with extension into extracranial soft tissue. Rest of the structures were normal on the scan. On consultation with a local physician, he was referred to a neurosurgeon. The boy underwent craniotomy with question mark shaped incision on the scalp with gross total excision of the mass. The histopathological report was suggestive of malignant round cell tumor, possibly primitive neuroectodermal tumor (PNET), without any osteoid or chondroid differentiation, with infiltration of bone [Figure 2], most probably Ewing's sarcoma. Immunohistochemistry study showed the cell to be positive for vimentin, CD99, and FLI1 while negative for synaptophysin, glial fibrillary acidic protein (GFAP), and epithelial membrane antigen (EMA). MIB index was 40% [Figures 3 and 4]. Skeletal survey was normal. Bone scan was suggestive of no abnormal uptake [Figure 5]. Bone marrow biopsy showed no malignant cells. The patient was planned for adjuvant chemotherapy and radiotherapy.

Figure 1

Magnetic resonance imaging scan showing the skull-based lesion of left parietal bone

Figure 2

Histopathology slide (×40) showing small, round, blue cell

Figure 3

Immunohistochemistry slide showing the CD99 staining

Figure 4

Immunohistochemistry slide showing FLI1 staining

Figure 5

Technetium-99 bone scan showing no abnormal uptake elsewhere in the body

DISCUSSION

Ewing's sarcoma of the cranial bones is a rare entity with only 71 cases reported so far in published literature. These are grouped under the PNET family of tumors by the WHO classification and show small round blue cells.[2] The most common bones involved in cranium are the frontal bone, occipital bone, parietal bone, and the base of the skull. Sphenoid and ethmoid are the less commonly involved structures among the cranial bones.[3] The differential diagnoses for such cases are PNET, metastatic neuroblastoma, chordoma, and lymphoma. Less common differential diagnoses are rhabdomyosarcoma, osteosarcoma, meningioma, desmoplastic small round cell tumor, plasmacytoma, and solitary metastasis.[4] The routine histopathology study shows sheets of round blue cells with high nucleocytoplasmic ratio with scant glycogen-rich eosinophilic cytoplasm and round nuclei. The cells stain positive with periodic acid-Schiff. The conclusive differentiation between these requires immunohistochemistry study which can confirm the true identity of the tumor cells.[567] MIC-2 is a specific marker for Ewing's sarcoma and peripheral primitive neuroectodermal tumors.[8] FLI1 is another marker that can be reliably applied to differentiate small round cell neoplasms of soft tissue.[910] The combination of CD99 and FLI-1 is the method of choice for the diagnosis of EWS/PNET.[11] The immunohistochemistry in our case was found to be positive for vimentin, CD99, and FLI1 while negative for synaptophysin, GFAP, and EMA which indicates toward Ewing's sarcoma. A prompt diagnosis and treatment are essential for long-term survival in these patients with Ewing's sarcoma. The standard treatment is a multidisciplinary approach that includes radical surgery, chemotherapy, and radiotherapy. Resection of each tumor should be as radical as possible to achieve negative margins, minimize tumor mass, and enhance the effect of adjuvant therapy. A course of radiotherapy to the residual tumor followed by a four-drug regimen (vincristine, adriamycin, cyclophosphamide, and actinomycin D) is described to be superior to a three-drug regimen (vincristine, adriamycin, and cyclophosphamide). Radiotherapy is delivered up to a dose of 40–50 Gy in 1.8–2 Gy fractions as adjuvant therapy. The overall prognosis is good with multidisciplinary treatment including complete surgical resection followed by multiagent adjuvant chemotherapy and local radiotherapy. In a case series of 14 patients with cranial Ewing sarcoma by Desai et al., the mean follow-up achieved was 4.25 years (range from 8 months to 8 years) with a 5-year survival >57%.[1]

CONCLUSION

Ewing's sarcoma presenting as a primary lesion of the cranium is a rare occurrence. Definitive diagnosis in such cases can be challenging and should be accompanied by a thorough immunohistological study to rule out the numerous differential diagnoses. Early establishment of exact diagnosis followed by prompt multidisciplinary treatment is crucial. The effective treatment option includes primary surgical excision with clear margins which should be followed by multiagent adjuvant chemotherapy and subsequent local radiotherapy. Optimal treatment provides a good prognosis when availed early in the course of the disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.