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CC BY 4.0 · Indian Journal of Neurosurgery
DOI: 10.1055/s-0045-1812474
Letter to the Editor

Primary Intracranial Ewing Sarcoma Mimicking Glioblastoma in an Adult Indian Male

Autoren

  • Mohd Arshad

    1   Department of Neurosurgery, Dr. Sampurnanand Medical College, Jodhpur, Rajasthan, India

  • Himanshu Jindal 

    2   Ganesh Shankar Vidyarthi Memorial Medical College, Kanpur, Uttar Pradesh, India

  • Shailesh Thanvi

    1   Department of Neurosurgery, Dr. Sampurnanand Medical College, Jodhpur, Rajasthan, India

  • Aasma Nalwa

    3   Department of Pathology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
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Intracranial Ewing sarcoma (IES) is a primitive neuroectodermal tumor of the peripheral nervous system consisting of undifferentiated small and round cells.[1] Ewing sarcoma typically arises in the bones or soft tissues in children and adolescents, and its intracranial occurrence in adults is exceptionally uncommon, comprising only 0.03% of all intracranial tumors.[2] [3] [4] [5] Ewing sarcomas arise due to peculiar balanced chromosomal translocations, with 85 to 90% of patients having t(11,22) (q24;q12) translocation resulting in the EWSR1-FLI1 fusion gene. In approximately 10% of patients, the t(21,22) (q22;q12) translocation is the second most common, resulting in the EWSR1-ERG fusion gene.[5] [6] [7] In approximately 3% of patients, EWSR1 gene fusion with other ETS family transcription factors, such as FEV1, is seen.[5] Publications on IES are scarce, most of which are isolated case reports.[1] Neuroimaging techniques, histopathological examination with immunohistochemical staining, and cytogenetic/molecular studies remain crucial for accurate diagnosis. Treatment protocols typically involve multimodal approaches, including surgical resection, chemotherapy, and radiotherapy. However, the optimal management strategy for adult primary IES (PIES) is not well-defined due to the limited available evidence.[8] Given the extreme rarity of PIES, it is not often included in the usual differentials in most clinical scenarios.[2] We aim to contribute to the scarce data on adult PIES by detailing the clinical course of a 24-year-old male patient with Ewing sarcoma in the left frontal lobe. The tumor was misinterpreted as glioblastoma on initial histopathology.

A 24-year-old man presented with a week-long history of headache (persistent, unrelieved by medication) accompanied by several days of vomiting and blurred vision. An initial noncontrast magnetic resonance imaging (MRI) of the brain revealed a large intra-axial mass lesion with both solid and cystic components in the left frontal lobe. A subsequent contrast-enhanced MRI provided further details, revealing a large tumor with the “cyst-with-mural-nodule” morphology in the left frontal lobe. The tumor measured 7.5 × 4.8 × 6.3 cm, with the solid component constituting almost half of the lesion and located toward the surface cortex, while the cystic component was present toward the white matter, distorting the frontal horns of the left and right lateral ventricles. The cystic portion showed hyperintense signals of fluid content relative to cerebrospinal fluid on FLAIR (fluid-attenuated inversion recovery), T1W, and T2W images ([Fig. 1A–D]).

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Fig. 1 (A) Sagittal T2-weighted MRI showing a large intra-axial mass lesion in the left frontal lobe with solid and cystic components. The solid component is seen toward the surface cortex, and the cystic portion, which contains hyperintense fluid relative to CSF, is located deeper toward the white matter. (B) Axial diffusion-weighted imaging (DWI) demonstrating restricted diffusion within the solid component of the mass, suggesting high cellularity typical of Ewing sarcoma. (C) Coronal T1-weighted post-contrast MRI highlighting the “cyst-with-mural-nodule” morphology of the lesion, with the solid component showing significant contrast enhancement, indicative of its aggressive nature. (D) Axial T2-weighted MRI showing the cystic component of the lesion with perilesional edema and a mass effect, displacing the adjacent brain structures. CSF, cerebrospinal fluid; MRI, magnetic resonance imaging.

The patient underwent a left frontal craniotomy with tumor decompression under general anesthesia. The procedure was uneventful, and the patient was transferred to the intensive care unit for further management. However, he developed an extradural hemorrhage necessitating re-exploration and a left temporoparietal craniotomy on the same day.

An excisional biopsy was performed, and the specimen was sent for histopathological analysis to determine the tumor's origin and type. Since the setting has limited resources, immunohistochemistry could not be done and initial histopathological examination suggested a glioblastoma. To differentiate Isocitrate Dehydrogenase (IDH)-wild versus IDH-mutant types of glioblastoma, the tissue block was sent to a higher center for immunohistochemical staining. Interestingly, histopathological examination at the higher center revealed a highly cellular tumor with extensive necrosis. Immunohistochemistry showed the tumor cells to be diffusely immunopositive for CD99, FLI-1, and NKX2.2 ([Fig. 2A–D]), and immunonegative for GFAP, Olig2, CD45, SALL4, NeuN, STAT6, and Chromogranin A. The Ki67 proliferation index was approximately 95%, indicating high proliferative activity.

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Fig. 2 (A) Low-power view showing a monomorphic appearing blue cell tumor with adjacent normal brain parenchyma (H&E x40X). (B) High-power view showing primitive-looking cells in sheets with occasional Homer–Wright rosettes (red arrow) and active frequent mitosis (black arrow), (H&E x400X). (C) The tumor cells are immunopositive for CD99 (IHC x100X), (D) and for NKX2–2 (IHC x100X).

Four days postoperatively, the patient experienced severe chest pain and was diagnosed with an anterior wall myocardial infarction, followed by three episodes of monomorphic ventricular tachycardia. He was managed conservatively in the cardiology care unit, where his stay was uneventful. Postoperatively, the patient exhibited no neurological deficits. High-resolution computed tomography (CT) thorax and noncontrast CT abdomen showed no evidence of additional lesions. A postoperative CT of the brain confirmed near-complete tumor decompression. The patient was subsequently put on an adjuvant chemotherapy regimen comprising etoposide and ifosfamide. Mesna was added for ifosfamide toxicity.

IES is a rare entity, and its demarcation from other similar intracranial tumors is crucial for accurate diagnosis and effective management. Authors in published studies have referred to IES as “an entity of unacquaintance,” underscoring its importance and rarity in the differential diagnosis of intracranial neoplasms.[2] The clinical features are varied, but headache is the most consistent symptom. Other signs and symptoms at presentation reported in previous cases include vision problems, seizures, hyposmia, papilledema, vomiting, fever and malaise, tinnitus, dizziness, hemiparesis, imbalance, and memory and mental status impairment.[1] [2] [4] [8] [9] [10] Most IES cases reported in the literature are in the pediatric age group.[1] [2] [9] [11] In our case, it was found in a 24-year-old adult, which further adds to the rarity of this case.

The radiological presentation of IES can be variable, often mimicking other intracranial lesions. Advanced neuroimaging techniques may provide valuable insights into the tumor's characteristics and aid in preoperative planning.[10] In our case, MRI had revealed a left frontal lobe mass with both solid and cystic components similar to radiological findings in previously published cases.[2] [4] [10] [11]

Immunohistochemical analysis plays a crucial role in the diagnosis, with markers such as CD99, FLI1, and NKX2.2 typically demonstrating positivity in IES. Immunohistochemical analysis also aids in differentiating IES from other intracranial neoplasms. Diffuse membranous CD99 positivity is a highly reliable and sensitive marker for Ewing Sarcoma. However, although sensitive, CD99 is not a specific marker for Ewing sarcoma as it can be found in other malignancies.[1] [5] [12] [13] Molecular studies (via reverse transcription polymerase chain reaction/fluorescence in situ hybridization) and cytogenetic studies revealing balanced translocation of EWSR1 gene conspicuous of Ewing sarcoma are currently gold standard tests for confirmatory diagnosis of Ewing Sarcoma.[4] [13]

Due to the extreme rarity of PIES, the current body of evidence for management strategies for the tumor remains limited. The optimal management of IES remains unclear due to its rarity, and no established standard treatment protocol exists.[1] [8] [9] [10] IES is treated similarly to Ewing sarcoma anywhere else in the body. The current consensus on treating Ewing sarcoma of bone involves multiagent therapy, which is believed to be highly efficacious; however, its efficacy for IES is doubtful.[8] Surgical resection remains the mainstay treatment.[9] Surgical resection, along with chemotherapy and/or radiotherapy, provides favorable results.[4] [8] [9] As per the EE99 protocol, the induction chemotherapy regimen involves using VIDE—vincristine, ifosfamide, doxorubicin, and etoposide. The central nervous system penetration of ifosfamide is believed to be good, while that of others is contentious.[1] [14] Given the resource constraints, ifosfamide and etoposide were used in our case.

In terms of prognosis, the outcomes for patients with PIES vary. A study reported a 3-year event-free survival of 64% and an overall survival of 70% for patients with PIES.[1] In our case, early surgical resection coupled with adjuvant chemotherapy was done to mitigate the risk of recurrence. While the patient in our case had a favorable postoperative course, long-term follow-up is essential due to the potential for late recurrence, as highlighted by similar cases.[2] [9] [10]

PIES in adults is an extremely uncommon occurrence and is often missed on differentials in routine clinical scenarios. It is highly malignant and bears a poor prognosis. Accurate diagnosis becomes difficult in scenarios where it mimics other intracranial neoplasms. Given the scarcity of reported cases, there is a pressing need for multicentered collaborations and long-term follow-up studies to better elucidate the natural history, prognostic factors, and optimal management strategies for IES. Such efforts would enhance our understanding of this rare entity and potentially lead to the development of targeted therapies and improved patient outcomes.



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Artikel online veröffentlicht:
14. Oktober 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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