Ewing's sarcoma was originally named for James Ewing in 1921, who initially described the tumor as a diffuse endothelioma. It is now considered to be a tumor within the primitive neuroectodermal tumor class.28
In the Intergroup Ewing's Sarcoma Study (IESS), Ewing's sarcoma comprised ~4% of the primary bone tumors of the head and neck. In this review, the most commonly involved site in the head and neck was the skull (11 of 29), followed by the mandible and maxilla. Only one patient had tumor involving the ethmoid sinus. In this group, typical symptoms were related to mass effect of the tumor.3
The most common presenting symptom was a mass or swelling at the site of the tumor. Other symptoms reported were related to ocular or cranial nerve involvement, such as oculomotor dysfunction or proptosis.3
There are very few reported cases of Ewing's sarcoma involving the paranasal sinuses. A review of the literature revealed 14 articles, the majority of which are case reports. Details of these cases are listed in Table .3,4,5,6,7,8,9,10,11,12,13,14,15
The diagnosis is made by pathological analysis.28
Ewing's sarcoma is one of the small, blue, round cell tumors of childhood. Histologically, the differential diagnosis includes lymphoma, rhabdomyosarcoma, neuroblastoma, and primitive neuroectodermal tumor (PNET).29,30,31,32
In addition to histochemical analysis, molecular testing is often necessary to identify signature translocations involving the EWS
gene (balanced translocation involving chromosomes 11 and 22). These translocations are detectable with both reverse transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) in formalin-fixed, paraffin-embedded tissue. Bridge, et al reported 100% sensitivity and specificity for a commercial EWS
probe, whereas RT-PCR had a sensitivity of 54% and specificity of 85%.33
The prognosis for this tumor has progressively improved over the last decade due to a combination of increased awareness and recognition of the diagnosis as well as the improvement in multimodality therapy. For patients with Ewing's sarcoma of the head and neck, tumors arising in the maxilla or mandible have had the best overall prognosis.3
Treatment usually consists of multimodality therapy incorporating chemotherapy, radiation therapy, and surgery. Overall, the use of chemotherapy and radiation therapy has greatly improved disease-free survival. The Cooperative Ewing's Sarcoma Studies 1981 (CESS-81) compared three treatment regimens: surgical resection, primary radiation therapy, and combination surgery and radiation therapy, with 5-year survival rates being 54, 43, and 68%, respectively. However, a follow-up study looking at 3-year follow-up by the same group (CESS-86) showed no statistical difference within the treatment groups (62 to 67%), thus advocating potential for radiation alone when surgery would lead to significant morbidity. The authors concluded that combined local treatment (surgery and radiation) improved locoregional control and probably improved survival in high-risk patients.34
The use of adjuvant chemotherapy has been shown to have positive effects. The IESS-II reported a disease-free survival rate of 68% with their protocol using adjuvant vincristine, Adriamycin, and cyclophosphamide (VACA).35
The use of neoadjuvant IF and ET has been shown to be effective in patients who have relapsed after treatment with VACA; however, the addition of IF and ET to the VACA regimen has not been shown to have any additional advantage.36
Based on the available literature and our experience with Ewing's sarcoma localized to the sinonasal cavity and skull base, a multimodality treatment regimen is the treatment of choice. Initial chemotherapy is followed by either surgical resection, radiation therapy, or a combination of both, depending on the location of the tumor at initial presentation. If the tumor is thought to be surgically resectable without significant morbidity, surgery is suggested after completion of chemotherapy. If the tumor is thought to be unresectable or if surgery would result in significant morbidity, proton beam radiation therapy is used for local control.
In our two cases of Ewing's sarcoma involving the sinonasal cavity and anterior cranial base, a rarely reported entity, neither patient had evidence of metastatic disease at the time of presentation. Because surgical resection for both patients would have potentially required anterior craniofacial resection with orbital exenteration to achieve en bloc resection with negative margins, the decision by our multimodality group was to proceed with induction chemotherapy followed by proton beam radiation therapy for local control. One patient underwent preoperative endoscopic subtotal removal to improve the radiation field and facilitate adequate sinus drainage during radiation therapy. She had no postsurgical sequelae, radiation therapy was not delayed, and the proton treatment volume in the maxillary sinus was significantly reduced.
In the group of patients, where total surgical resection would result in significant morbidity, subtotal resection via an endoscopic approach (with minimal morbidity) might be useful to reduce the proton treatment volume necessary. In addition, for patients with tumors involving the sinonasal cavity, endoscopic sinus surgery to facilitate sinus drainage and minimize sinus obstruction and infection might also be a helpful part of the treatment regimen. Both patients underwent endoscopic sinus surgery after completion of treatment. This was performed to confirm there was no evidence of persistent disease at the site of the original tumor, but the surgery also addressed blockage of the frontal outflow tract concurrently. Both patients had resolution of frontal headaches after the endoscopic sinus surgery, and there has been no evidence of recurrent frontal sinus opacification.