Primary, Dural-based, Ewing sarcoma in a pediatric patient: presentation of a rare tumor entity with literature review

Primary Ewing’s sarcoma originating from the calvaria bone and/or underlying Dural involvement has been reported relatively rarely in the literature. Those originating from the dura and invading the bone above it in both directions, both towards the brain parenchyma and via the dura, are even rarer. We present a case of a 14-year-old girl with no known focal neurological deficit who presented with the complaint of vertigo for only 2 months. In neuroradiological examination, the left frontoparietal region of the brain showed the presence of a tumor originating from the dura, invading both bone and brain parenchyma. No other tumor location was discovered after radiological examination. Since the patient had a shift in the brain and progressive loss of strength on the right side, the patient was taken to surgery for tumor excision. The frozen result sent per-operatively was consistent with a round blue cell tumor. Adjuvant chemotherapy treatment was given to the patient after the definitive pathology report was compatible with Ewing’s sarcoma. The patient had an uneventful neurological recovery without permanent neurological deficit. When the patient was kept under close clinical and radiological surveillance 1 year after the operation, no recurrence of the disease was observed. Bone marrow biopsy results and pet computerized tomography results confirmed the case of primary intracerebral Ewing sarcoma. This case illustrates an extremely rare location of primary Ewing’s sarcoma with a set of clinical signs and symptoms extremely rare for this location of this rare disease entity.


Introduction
Ewing sarcoma (EWS)/primitive neuroectodermal tumor (PNET) is a highly malignant small round cell tumor that predominantly affects bone and soft tissue. EWS is currently considered the second most common pediatric primary bone malignancy, with osteosarcoma being the most common [1][2][3][4][5][6]. It originates mainly from the long bones or the axial skeleton, including the pelvis, ribs, and vertebrae. It is defined as an undifferentiated, malignant, small round cell tumor that prefers bone and soft tissues. James Ewing first described it as "diffuse bone endothelioma" in 1921.
Primary intracranial EWS has been demonstrated extremely rarely. It is considered a distinct subtype of extraosseous EWS, based on the fact that its most common origin is the dura mater and is estimated to constitute 1-4% [7,8].
Ewing sarcoma breakpoint region 1 (EWSR1) and several common gene fusions are well known. In this tumor, approximately 85-90% of EWS/PNETs contain a t(11;22) chromosomal translocation, and 10-15% have a t(11;22) chromosomal translocation. Considering the fact that it is primary intracranial, EWS is an entity that is not very well and comprehensively defined in the literature clinically and radiographically. In this case, we present a case with its symptoms, histopathological features, and follow-up results.

Historical background
The 14-year-old girl was seen several times by the general pediatrician for dizziness for 2 months. After the patient had complaints of numbness and numbness on the right side for the past 1 week and weakness on the right side, magnetic resonance imaging of the patient showed a mass lesion (Fig. 1). Dural-based brain parenchyma is under pressure and causing shift. A case of meningioma with heterogeneous enhancement and thought to be Dural origin was considered. The patient was started on anti-epileptic therapy, levetiracetam. No tumor was found in a different part of the body in the preoperative abdominal ultrasonography and computed tomography examinations. The cranial computerized tomography showed that the bone or dura eroding the bone developed hemiparesis on the right side of the patient while she was in the hospital. The patient was taken to an urgent surgery.

Management and prognosis
With a bi-coronal skin incision, a wide fronto-parieto-occipital craniotomy flap crossed to the opposite side was used. Peroperative image of the mass showed Dural-based and penetrating brain parenchyma. Due to its proximity to the sagittal sinus, preoperative magnetic resonance venography (MRV) imaging was performed on the patient (Fig. 2). MRV showed sagittal sinus was intact and functional. The mass was excised gross totally and the tissues around the intact sagittal sinus were left (Fig. 3). The Dural parts and bone to which the mass was attached were excised and sent to pathological examination. Per-operative histopathological examination result was compatible with malignancy consisting of small blue round cells. Duraplasty and cranioplasty were performed in the same session using synthetic dura graft (Duragen, Integra, USA) and titanium mesh. Postoperative contrast-enhanced MRI revealed that the mass was gross totally excised and there was no intracranial hemorrhage (Fig. 4). Preoperative right-sided weakness continued in the postoperative period, and intravenous 3% sodium solution was given for 1 week as anti-edema treatment. After the anti-edema treatment, the patient's neurological deficits improved at the end of the 1st week.
At the end of the 3rd postoperative week, the patient's pathological examination was completed and the EWS was confirmed. Bone marrow biopsy and peripheral blood smear tests were performed on the patient. However, no tumor was detected in any part of her body. The patient was given adjuvant chemotherapy. The patient, who did not have any neurological complaints, came to the 6th month follow-up. Contrastenhanced cranial magnetic resonance imaging was performed (Fig. 5). No recurrence was detected in MRI, and the patient was included in the follow-up list after receiving the consultations of the pediatric hematology and oncology departments. No additional chemotherapy or radiotherapy was given.

Results
The patient received additional therapy consisting of chemotherapy and radiotherapy as is commonly used in patients with EWS. Chemotherapy included a combination Fig. 1 a In the T1 section with axial contrast, a lesion close to the sinus with the widest diameter of 55 mm is seen. b In contrast-enhanced T1 coronal section, it is seen that the mass shifts due to the compression effect. c T1 section with sagittal contrast shows compression on the brain parenchyma and edema of the mass Although the mass has surrounded the sagittal sinus, minimally filling is seen in the sinus of vincristine, cyclophosphamide, doxorubicin, and etoposide alternating with ifosfamide. No additional radiotherapy was given to the patient. Additional imaging evaluation was performed 3 months after surgery and then every 3 months until the completion of the 1-year follow-up period. In all serial magnetic resonance scans, after intravenous contrast administration, no pathological contrast administration that could be sensitive to possible local tumor recurrence was detected. Neurological examination was repeated at each follow-up, but no change was observed in the neurological examination.
Cranioplasty of the patient was performed in the same session, since it was difficult to repair the resected bone flap with allogeneic graft material due to the toxicity of chemotherapy reported in previous cases [9,10]. Cranioplasty was performed by placing a titanium mesh. However, as reported in other cases, anti-edema treatment was continued for 1 week in the postoperative period. The patient was followed up for 1 year postoperatively.

EWS/PNET is a malignant tumor of bone and soft tissues.
This pathology, which occurs in childhood and young adults, is seen equally in men and women. This aggressive neoplasm is a treatable malignancy with a good prognosis in patients younger than 16 years of age [11].
Primary EWS is relatively rare. Although EWS looks the same as PNET under the microscope, these tumors differ in histogenesis, molecular features, and clinical behavior. They described the imaging features of the primary intracranial EWS. Dural adhesion, containment, lobularity, and intense diffuse enhancement were consistent features of intracranial EWS, according to their review [12]. Histologically, they are like other small round blue cell tumors in general and PNET in particular and are often misdiagnosed as secondary. Immunohistochemistry for CD99 encoded by the MIC2 gene is usually positive in the primary intracranial EWS and Fig. 3 a Intradural extension of the mass is seen after craniotomy. b Adherent parts of the mass to the sagittal sinus were left in order not to damage the sinus. c Extraaxial parts of the mass that invade the bone are seen. d It did not cause any damage to the brain parenchyma after gross total excision. Only a small piece around the sinus had to be left. e Duraplasty was performed with the synthetic dura graft Duragen (Integra, USA). Bone structure was excised and titanium mesh was placed in the same session and cranioplasty was performed  , and sagittal (c) T1-weighted magnetic resonance images taken with intravenous contrast at the 6th month follow-up, and after adjuvant chemotherapy was given to the patient, no increase in residual mass size was observed 1 3 in most cases helps distinguish it from PNET that does not express this antigen. However, it is worth noting that this antigen is not entirely specific and can be encountered in several other CNS tumors, including hemangiopericytoma.
Recent advances in the molecular classification of PNET and intracranial EWS have allowed a clear pathological distinction between these 2 entities. It shows diagnostic chromosomal translocations involving a fusion of the intracranial EWS with a member of the EWS gene with a member of the Ets family of transcription factors, leading to expression of chimeric fusion oncoproteins. This characteristic feature is not found in PNET. Instead, the most common molecular abnormalities involve isochromosome 17q and myc gene amplifications in patients with medulloblastoma or, less commonly, supratentorial PNET [13].
Our case shows radiological and histological features similar to several primary intracranial EWS cases previously described in the literature. No tumor was seen in chest, abdomen, or pelvis on computed tomography. In addition, bilateral bone marrow biopsies and technetium-99 m bone scan were negative, confirming the case was primary EWS.

Conclusion
Intradural and concurrent extradural extension with erosion of adjacent frontal and parietal bone associated with Dural invasion and intraparenchymal extension is an extremely rare condition for primary EWS. The overall clinical scenario is further complicated by the rare combination of clinical and neurological manifestations that lead to the diagnosis of the disease. The aim of this article is to compile the cases of primary intracranial EWS previously reported in the literature and to compare them with their results, to emphasize the fact that early diagnosis and effective treatment strategy of primary EWS is imperative and highly recommended to achieve a good overall outcome.
More specifically, regarding the contribution of our article to the scientific community, we would like to talk about some of the features of our case compared to other previously described cases in the literature. Unlike other cases, the first clinical symptom in our case was hemiparesis. Due to the rapid development of this focal neurological deficit seen with the anatomical localization of the tumors, our patient had to be operated without preoperative tumor investigation. The differences are as follows (Table 1). Based on a detailed MEDLINE search, it has been well reviewed in a recent article [10].