Case Report
Primary Intracranial Intra Axial Ewing’s Sarcoma: A Rare Case Report with Unusual Location & Short Review on Literature
Naresh Panwar*, Somnath Sharma and Devendra K Purohit
Department of Neurosurgery, SMS Medical College, Jaipur, India
*Corresponding author: Naresh Panwar, Department of Neurosurgery, SMS Medical College, Jaipur, Flat no.301, Shiv Sai Residency, Plot -727, Adarsh Nagar, Ashok Chowk, Rajasthan, India
Published: 20 Mar, 2018
Cite this article as: Panwar N, Sharma S, Purohit DK.
Primary Intracranial Intra Axial Ewing’s
Sarcoma: A Rare Case Report with
Unusual Location & Short Review on
Literature. Clin Surg. 2018; 3: 1946.
Abstract
Ewing's Sarcoma (ES) is one of the frequently seen and catastrophic malignancies of childhood
incriminate long bones and soft tissue. As far intracranial manifestations of the disease are
concerned, which are extremely rare in reality, Most of the reported cases of ES involving Central
Nervous System (CNS) represent secondary metastases from extra cranial sites. Although there are
very few cases reported of primary Ewing's sarcoma of cranium. A search of the literature suggests
that these tumors are mostly dural based or extra axial mimicking as meningeal tumors and most
commonly seen in younger population. We present the clinical, radiologic and pathologic findings
of an primary intracranial intra axial Ewing sarcoma/pPNET in a 42-year-old male located in left
Parieto-occipital sub cortical zone, and radiologically presenting as Glioblastoma Multiforme
(GBM).This site is highly unusual for intra axial ES, and to the best of authors knowledge this is
third case of intra-axial intra parenchymal ES/pPNET.
Keywords: Ewing sarcoma/peripheral primitive neuroectodermal tumor; Primary intracranial
intra-axial; Central nervous system
Introduction
Ewing Sarcoma/peripheral Primitive Neuroectodermal Tumor (ES/pPNET) is aggressive, highly malignant, embryonal tumor of diaphysis of long bones, flat bones and soft tissues commonly occurred in pediatric age group [1]. These tumors composed of undifferentiated or poorly differentiated neuroepithelial cells and belong to a large family of small-blue-round-cell tumors. Intracranial primary ES/pPNET is extremely rare and cause is considered metastasis from extra cranial location. Most of the available literature is in the form of case reports. An intra-axial presentation of these tumors often misdiagnosed as central nervous system PNET (c-PNET) or as other primary intracranial neoplasm, clinically and radiologically. The diagnostic challenges, management issues should be address properly to broaden further insight regarding these tumors. As the tumor presents in young age, long-term survival remains a challenge in management of ES/pPNET patients. We report a case of intracranial intraparenchymal ES/pPNET presenting as heterogeneously enhancing high grade glioma in a 42-year-old male with complains of seizure and unconsciousness, an unusual radio pathological presentation.
Case Presentation
A 42-year-old male presented with a single episode of generalized tonic-clonic seizure followed
by unconsciousness one month prior to admission at our institution, Since then he developed mild
to moderate intensity bifrontal headache and later on he had history of vomiting. On examination,
patient was conscious, oriented comfortable and co-operative. His Glasgow coma score was E4 V5
M6 (15/15). Contrast-Enhanced Computed Tomography (CECT) showed an intra-axial relatively
defined hyper dense mass lesion measuring about 7 cm × 4.8 cm × 8.8 cm in size in left parietooccipital
region, which showed heterogeneous contrast enhancement (Figure 1a-1d). Magnetic
Resonance Imaging (MRI) brain was done with T1 & T2 Weighted sequence, Post Gadolinium
contrast and Diffusion Weighted Imaging (DWI) on 1.5 Tesla MR Scanner. Which showed a well
defined, solid cystic mass lesion in left parieto-occipital convexity with significant perifocal white
matter edema. Post contrast images showed thick wall nodular peripheral enhancement and medial
limit of tumor extending till ependymal ventricular margin. The patient underwent left parietooccipital
craniotomy and gross total removal with decompression of the lesion was achieved.
Histopathologically neoplasm was predominantly revealing
hyper cellular and hypo cellular areas. The cellular areas are
comprised of small round cells in sheets, with scanty cytoplasm and
vesicular pleomorphic hyper chromatic nuclei with occasional cells
show prominent nucleoli. With a primary histological differential
diagnosis of Round cell tumor, immunohistochemistry was done
to further characterize the neoplasm. Tumor cells were negative for
synaptophysin, Glial Fibrillary Acidic Protein (GFAP), cytokeratin,
Leukocyte Common Antigen (LCA), Epithelial Membrane Antigen
(EMA). Tumor cells showed strong membranous immunoreactivity
for CD 99 antigen (using B Biocare Monoclonal Mouse Anti-Human
MIC-2, clone 12E7 with identical reactivity as monoclonal antibodies
HBA-71 and RFB-1) (Figure 2a-2d). The Ki-67 labeling index was
30% with a diagnosis of ES/pPNET Extensive workup was done
including CECT scans of the thorax, abdomen, and pelvis, to search
for extra cranial primary sites or metastatic deposits, which were all
negative. Final diagnosis was primary ES/pPNET.
Figure 1
Figure 1
(a,c) Post Gadolinium contrast MR Scan showed a well defined, solid cystic mass lesion measuring about 5.8 cm x 4.8 cm x 1.6 cm in size in left
parieto- occipital convexity with thick wall nodular peripheral enhancement, (b)-T2 weighted showed hetrogenous hyperintese mass with midline shift, (d) Contrastenhanced
computed tomography (CECT) showed an intra-axial relatively defined hyperdense mass lesion left parieto- occipital region with perilesional edema).
Discussion
An American pathologist James Stephan Ewing (1866-1943)
first described the tumor, establishing that the disease was highly
aggressive, malignant and different from the known malignancies of
first half of 20th century [2]. In 1920; he published his first work on a
new kind of malignant osteoma, which later received his name. Since
last approximately more than 100 years Ewing's sarcoma remains a
challenging and lethal malignant pathology of pediatric age group
and most frequently originates in the diaphysis long bones (47%),
pelvis or ribs [3]. The involvement of skull is rare and hardly less
than 4% of total cases, with the frontal and parietal bones being the
most common location [4,5]. In past two decades, Ewing Sarcoma/
peripheral Primitive Neuroectodermal Tumor (ES/pPNET) has gain
popularity as a discrete disease entity that affects young adults, with
indistinguishable sex propensity. When we reviewed the available
literature on ES/pPNET affecting Central Nervous System (CNS),
Which is extremely rare, these tumors are usually located either
dural based supratentorially or involves the paravertebral regions of
the spine [6]. Due to radiological and histological similarity, when
these lesions arise in the intraparenchymal compartment leads
to diagnostic challenge and commonly mimics as central –PNET
(c-PNET) or other primary CNS tumors.
If we talk on occurrence of cranium ES, these two series provide
brief insight that “how less the entity actually”??. An epidemiological
study of 2500 cases of brain tumor conducted by Paulus et al. [7] found
only 9 cases of histopathological proven sarcoma, and ultimately one
case turn out as ES. A recent retrospective epidemiological analysis
332 cases of ES during a span of 11 years conducted by Krishnamani
et al. [8] at their institution detected only 7 cases of ES that primarily
involved skull. Further knowledge on epidemiology of cranium ES is
enhanced by Vandenheuvel KA et al.[9]. They reviewed the available
literature on the topic and described the detail of 26 cases reported
so far, they found that out of 26 cases only two cases were of primary
intra axial intraparenchymal ES/pPNET of the CNS that have been
reported in the English literature [9]. To the best of our knowledge
this is the third case report of primary intra axial intraparenchymal
ES/pPNET of the CNS. Certainly, Jay et al. [10] was the first who
describe a case of histopathologically proven medulloblastoma in
posterior fossa but on further molecular workup demonstrated the
t(11;22) (q24;q12) translocation, which ultimately turns out ES/
pPNET.
Diagnosis requires a histopathological examination,
immunohistochemistry, and cytogenetics. The histological examination reveals that these tumors are composed of nearly
uniform population of round to oval cells with scanty, basophilic
cytoplasm, undifferentiated neuroectodermal cells with distinct
immunohistochemical and/or electron microscopic features of glial
or neuronal differentiation. Immunohistochemistry for CD 99 (MIC-
2 gene product) shows strong membrane positivity in more than 97%
of the patients of ES/pPNETs [11]. The chromosomal translocation
t(11, 22) (q24;q12), detected by in situ hybridization technique is
found in approximately 90% of these tumors.
Being a rare category of diseases, still there is no certain
defined therapeutic protocol for management of patients with
ES/pPNET affecting the CNS. However, available literature and
studies conducting so far suggest that a multidisciplinary treatment
approach is necessary. Although standard treatment guidelines for
primary intraparenchymal ES/pPNETs is not available, so we deal
our case as per treatment protocol for skull ES. Concisely speaking,
a multidisciplinary approach, with a combination of different
modalities of treatment, is preferred way of choice to treat this entity.
ES/pPNET is also radiosensitive and the dose of 1.5 to 2 gy/days for 5
days/weeks is recommended followed by four drug CT regime. Due
to the rarity of diseases, the prognosis of Es/pPNET is not clearly
known.
Figure 2
Figure 2
(a,b) The cellular areas are comprised of small round cells in sheets,
with scanty cytoplasm and vesicular pleomorphic hyper chromatic nuclei ( a-
4 x & b-10 x view). (c) Negative for synaptophysin, glial fibrillary acidic protein
(GFAP), (d) Tumor cells showed strong membranous immunoreactivity for
CD 99 with identical reactivity as monoclonal antibodies HBA-71.
Conclusion
The case reported here raises necessity regarding further awareness of this entity ES/ pPNET, its rare presentation, diagnostic challenges and appropriate management protocol. We suggest that, ES/pPNET has to be kept in mind in the differential diagnosis of intracranial especially dural based tumors. This case also highlights that we cannot deny the presence of isolated primary intracranial intra-axial Ewing's sarcoma.
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