Calvarial Ewing's sarcoma, a rare childhood tumor: Report and a review of literature
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_777_16
Source of Support: None, Conflict of Interest: None
Calvarial Ewing's sarcoma (CEWS) is a round cell sarcoma which occurs rarely in children. The optimum management of CEWS requires a multidisciplinary treatment approach consisting of surgical resection followed by radiotherapy and chemotherapy. We report two cases of CEWS who underwent wide resection followed by adjuvant chemotherapy. We also review the literature on CEWS.
A 12-year old child presented with a painless swelling over the vertex of the head. A plain radiograph showed an extra-axial lytic lesion with a sunburst appearance. Magnetic resonance imaging (MRI) with venography revealed an enhancing extradural lesion causing displacement and narrowing of the superior sagittal sinus [Figure 1]a,[Figure 1]b,[Figure 1]c,[Figure 1]d,[Figure 1]e,[Figure 1]f. The patient underwent a wide excision with a 1-cm normal margin. Postoperatively, the patient underwent chemotherapy and radiotherapy and remains disease free after 30 months.
A 20-month old child presented with a left temporal swelling. The magnetic resonance imaging (MRI) showed an extra-axial lytic lesion with homogenous enhancement [Figure 2]a,[Figure 2]b,[Figure 2]c,[Figure 2]d. The patient underwent a left temporal craniectomy and gross total excision with a 2-cm margin [Figure 3]a and [Figure 3]b. Postoperatively, he underwent chemotherapy and radiotherapy and remains disease free after 12 months.
Ewing first described this tumor as a “diffuse endothelioma of the bone” in 1921 in a report of six similar cases along with their radiographic appearances, a description which holds good nearly a century later. EWS is the second most common bony tumor of childhood and adolescence with a male predominance. Its incidence is more common in the temporal bone followed by the frontal and parietal bones. Calvarial EWS commonly presents as a localized scalp swelling; occasionally patients with an intracranial tumor extension present with signs of raised intracranial tension. In the present series, both the patients presented with a painless scalp swelling.
Other symptoms depend upon the location of the lesion, such as proptosis in the case of orbital involvement. There may be anemia, leukocytosis, elevated erythrocyte sedimentation rate (ESR), and elevated serum levels of alkaline phosphatase and C-reactive protein. An elevated lactate dehydrogenase level is associated with a poor prognosis. Investigations performed in a patient with CEWS include a helical computed tomography (CT) scan with reconstruction of the calvarium, MRI of the brain with a MR venogram to assess for the involvement of the sinuses, and a systemic workup to rule out distant metastasis. The appearance of CEWS is very variable. On CT scan images, the EWS may appear to be laminated (onion skin like), sclerotic, spiculated (sunburst appearance), or with a periosteal reaction, with soft tissue calcification seen infrequently. The CT scan reveals an iso- to hyperdense mass, which enhances with contrast. In both our cases, the tumors were hyperdense with a spiculated appearance. MRI reveals a low-to-intermediate signal on T1-weighted images, with a heterogeneous but prominent enhancement on gadolinium administration. “Hair-on-end” pattern of low signal striations may be seen on T2-weighted images. In both our cases, the masses were isointense on T1-weighted and T2-weighted images and exhibited intense enhancement after contrast.
A radioisotope bone scan is essential to rule out metastases and suspected recurrence at the margins following surgical resection. Ewing sarcomas demonstrate increased uptake on both gallium67-citrate and during all three phases of the technetium99m methylene diphosphonate bone scans.,,,,
Histological examination reveals that the tumor is composed of sheets of round cells with a scanty cytoplasm, having dark hyperchromatic nuclei. Cytoplasm is periodic acid-Schiff positive because of the presence of glycogen. Immunohistochemistry helps in differentiating it from other small round cell tumors including non-Hodgkin lymphoma, neuroblastoma, rhabdomyosarcoma, mesenchymal chondrosarcoma, retinoblastoma, desmoplastic small round cell tumor, osteosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and melanoma. On immunohistochemistry, the cells are positive for CD99, FLI1, and NSE and negative for desmin, leucocyte common antigen (LCA), and synaptophysin. CD99 is positive in more than 95% of the cases. Eighty-five percent of EWS are associated with translocation t (11;22)(q24;q12) resulting in a chimeric fusion transcript EWSFLI1. In another 10–15% of cases, the translocation t (21;12)(22;12) resulting in EWSERG (Ets-related gene) fusion is seen.
Favorable prognostic factors are age <15 years, female gender, absence of metastases at diagnosis, no regional lymph node involvement, peripheral location of the tumor, no history of treatment for different tumors before Ewing sarcoma is diagnosed, tumor &<8 cm in size, and initial LDH <170 IU/L.
Unfavorable prognostic factors include the fusion transcript detection in marrow or peripheral blood, overexpression of the p53 protein, and a high Ki67 expression; and loss of 16q.
EWS is often treated with neoadjuvant chemotherapy followed by surgical resection. The chemotherapeutic agents used are one of the following: doxorubicin, cyclophosphamide, vincristine, ifosfamide, actinomycin-D, and etopside. The purpose of preoperative chemotherapy is to: (1) eliminate systemic micro-metastases, (2) reduce the tumor size to enable resection along with optimal reconstruction, and (3) select post-operative chemotherapy. After the initial chemotherapy, patients with minimal or no residual viable tumor showed a better outcome.
For tumors involving the calvarium or the skull base, neoadjuvant treatment may help in decreasing the need for extensive resection, and in reducing the size of the defects to be closed, especially in the skull base. Radiotherapy is indicated for patients with tumor still present at the resection margins. As a rule, calvarial lesions are neither biopsied, nor is a routine search made for metastatic deposits at other sites. The aim is to proceed with direct surgical resection of the tumor.
However, recognizing that lesions such as EWS need an extensive preoperative evaluation is essential, we suggest that a needle biopsy must be performed, whenever feasible. In large extracranial calvarial lesions (not causing a rise in the intracranial pressure) located close to large sinuses, or in the skull base, such an approach is more likely to result in better local control of the disease. The size of the skull base defects to be repaired can also be minimized in this manner. Radiotherapy can then be given if there is suspicion of residual disease at the operative site.
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[Figure 1], [Figure 2], [Figure 3]