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Case Report
Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor R. Amita, S. Sandhyamani, Suresh Nair1, T. R. Kapilamoorthy2 Departments of Pathology, 1Neurosurgery, 2Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
Abstract
Address for correspondence: Dr. S. Sandhyamani, Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram ‑ 695 011, Kerala, India. E‑mail: [email protected] Received : 19‑05‑2014 Review completed : 26-06‑2014 Accepted : 10‑08‑2014
Central nervous system primitive neuroectodermal tumours (CNS PNET) are aggressive embryonal tumours composed of undifferentiated or poorly differentiated neuroepithelial cells seen in the pediatric age group. This is rare and only a handful of cases of ES/pPNET in CNS are reported. We report such a case in a 3 year old child. Reporting of more such cases is needed to better define these rare tumours of the dura.
Key words: Dura, Ewings Sarcoma, intracranial, primitive neuroectodermal tumors
Introduction Central nervous system primitive neuroectodermal tumors (CNS PNET) are aggressive pediatric embryonal tumors composed of undifferentiated or poorly differentiated neuroepithelial cells. This group includes CNS PNET NOS, neuroblastoma, ganglioneuroblastoma, medulloepithelioma, ependymoblastoma, and embryonal tumor with abundant neurophils and true rosette (ETANTR). [1] Ewings Sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) has been recently recognized to involve the CNS as well.
Case Report We report such a case in a 3‑year‑old child who presented with a single episode of generalized tonic clonic seizure of two‑minute duration. The patient was evaluated outside and started on anti‑tubercular treatment. One month later, the child developed sudden bifrontal headache, Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.141300
426
which was relieved with vomiting. On examination, the Glasgow coma scale was 15/15, with no neurologic deficits. There was bilateral papilledema. Magnetic resonance imaging (MRI) brain showed a well defined, significantly enhancing area of altered signal intensity in the frontal region of right cerebral hemisphere, with mass effect and adjoining meningeal enhancement [Figure 1a]. The patient underwent right frontotemporal craniotomy and gross total decompression of the lesion. Postoperative period was uneventful. Microscopic examination of the dura with an attached predominantly circumscribed neoplasm with areas of invasion into adjacent brain parenchyma was done. The neoplasm was predominantly composed of small round cells in sheets, with scanty cytoplasm and vesicular mildly pleomorphic nuclei with low mitotic activity [Figure 1b]. Focal areas of increased cellularity containing plump spindle‑shaped cells with brisk mitotic activity were seen [Figure 1c]. With a differential diagnosis between a PNET and gliosarcoma, immunohistochemistry was done to characterize the neoplasm. Tumor cells were negative for synaptophysin, chromogranin, glial fibrillary acidic protein (GFAP), cytokeratin, leucocyte common antigen (LCA), epithelial membrane antigen (EMA), and desmin while showing diffuse strong positivity for vimentin and S‑100. Tumour cells showed strong membranous immunoreactivity for CD 99 antigen (using Dako Monoclonal Mouse Anti‑Human MIC‑2, clone Neurology India | Jul-Aug 2014 | Vol 62 | Issue 4
[Downloaded free from http://www.neurologyindia.com on Thursday, September 25, 2014, IP: 202.177.173.189] || Click here to download free Android application fo this journal Amita, et al.: Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor
a
b
c Figure 1: (a) MRI brain shows a well-defined enhancing lesion in right frontal region with mass effect and adjoining meningeal enhancement, (b) Microscopy shows a small round cells neoplasm, and (b) Cellular areas with brisk mitotic activity. (b and c H and E, x100)
12E7 with identical reactivity as monoclonal antibodies HBA‑71 and RFB‑1). Reticulin stain showed a pericellular pattern. Most tumor cells showed periodic acid‑Schiff– positive, diastase‑sensitive material consistent with glycogen in the cytoplasm [Figure 2]. With a diagnosis of ES/pPNET involving dura and frontal lobe, WHO grade IV, the patient was started on chemotherapy with ifosfamide, adriamycin, and etoptoside and is doing well after four cycles.
Discussion The ES family of tumors most commonly involves the bone and soft tissue.[2] Primary intracranial ES/pPNET is a recently recognized entity of CNS PNET. There are less than 15 case reports of this entity in the literature.[3‑5] The diagnosis is based on correlating small round cell tumor histology with cytoplasmic glycogen positivity and immunohistochemistry showing positivity for MIC‑2 antigen and negativity for LCA, EMA, cytokeratin and desmin, and with characteristic translocation. The detection of p30/32 cell surface antigen (also known as the MIC2 gene product, which can be detected by antibodies such as HBA71 and O13) and reciprocal translocation (11;22) (q24;q12) are characteristic of this family of tumors.[2,4] The MIC2 gene product (CD99), present in nearly all ES/pPNET, is also detected in other small blue round cell tumors such as neuroblastoma, lymphoma, and rhabdomyosarcomas, where cells show cytoplasmic positivity. Distinct membrane staining is typical of ES/pPNET. Central PNETs are reported to be negative for CD99 staining.[3] Reports in literature indicate two patterns of meningeal involvement. [3] One characterized by a diffuse involvement of the cranial and spinal leptomeninges in Neurology India | Jul-Aug 2014 | Vol 62 | Issue 4
a
b
c
d
Figure 2: (a) Pericellular reticulin pattern, (b) Cytoplasmic Periodic-acid Schiff positivity, (c) Positive S100 staining and (d) membranous staining with CD99 (MIC-2)
the absence of a primary intraparenchymal or meningeal tumor and the other characterized by a localized dural‑based mass mimicking meningioma, as seen in our case. It is clinically important to distinguish ES/pPNET and central PNET as the treatment protocols and prognosis differ.[5] ES/pPNET has a long‑term disease‑free survival, which is uncommon in central PNET. These are relatively well‑circumscribed tumors, allowing gross total resection and their sensitivity to chemotherapy probably contributes for the better prognosis.[3] Awareness of this entity and differentiating it from the more common central PNET is important for the pathologist to help in guiding treatment.
References 1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of tumours of the central nervous system. Vol. 4. Lyon, France: IARC; 2007. p. 141‑6. 2. Amita RN, Sandhyamani S, Balasubramoniam KR. Primary primitive neuroectodermal tumor of lung: A case report. Indian J Pathol Microbiol 2013;56:479‑80. 3. Dedeurwaerdere F, Giannini C, Sciot R, Rubin BP, Perilongo G, Borghi L, et al. Primary peripheral PNET/Ewing’ sarcoma of the dura: A clinicopathologic entity distinct from central PNET. Mod Pathol 2002;15;673‑8. 4. Pekala JS, Gururangan S, Provenzale JM, Mukundan S Jr. Central nervous system extraosseous Ewing sarcoma: Radiologic manifestations of this newly defined pathological entity. AJNR Am J Neuroradiol 2006;27:580‑3. 5. Bano S, Yadav SN, Garga UC. Case Report: Intracranial peripheral primitive neuroectodermal tumor – Ewing’s sarcoma of dura with transcalvarial–subgaleal extension: An unusual radiological presentation. Indian J Radiol Imaging 2009;19:305‑7. How to cite this article: Amita R, Sandhyamani S, Nair S, Kapilamoorthy TR. Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor. Neurol India 2014;62:426-7. Source of Support: Nill, Conflict of Interest: None declared.
427
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
Case Report
Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor R. Amita, S. Sandhyamani, Suresh Nair1, T. R. Kapilamoorthy2 Departments of Pathology, 1Neurosurgery, 2Imaging Sciences and Interventional Radiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India
Abstract
Address for correspondence: Dr. S. Sandhyamani, Department of Pathology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram ‑ 695 011, Kerala, India. E‑mail: [email protected] Received : 19‑05‑2014 Review completed : 26-06‑2014 Accepted : 10‑08‑2014
Central nervous system primitive neuroectodermal tumours (CNS PNET) are aggressive embryonal tumours composed of undifferentiated or poorly differentiated neuroepithelial cells seen in the pediatric age group. This is rare and only a handful of cases of ES/pPNET in CNS are reported. We report such a case in a 3 year old child. Reporting of more such cases is needed to better define these rare tumours of the dura.
Key words: Dura, Ewings Sarcoma, intracranial, primitive neuroectodermal tumors
Introduction Central nervous system primitive neuroectodermal tumors (CNS PNET) are aggressive pediatric embryonal tumors composed of undifferentiated or poorly differentiated neuroepithelial cells. This group includes CNS PNET NOS, neuroblastoma, ganglioneuroblastoma, medulloepithelioma, ependymoblastoma, and embryonal tumor with abundant neurophils and true rosette (ETANTR). [1] Ewings Sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) has been recently recognized to involve the CNS as well.
Case Report We report such a case in a 3‑year‑old child who presented with a single episode of generalized tonic clonic seizure of two‑minute duration. The patient was evaluated outside and started on anti‑tubercular treatment. One month later, the child developed sudden bifrontal headache, Access this article online Quick Response Code:
Website: www.neurologyindia.com PMID: *** DOI: 10.4103/0028-3886.141300
426
which was relieved with vomiting. On examination, the Glasgow coma scale was 15/15, with no neurologic deficits. There was bilateral papilledema. Magnetic resonance imaging (MRI) brain showed a well defined, significantly enhancing area of altered signal intensity in the frontal region of right cerebral hemisphere, with mass effect and adjoining meningeal enhancement [Figure 1a]. The patient underwent right frontotemporal craniotomy and gross total decompression of the lesion. Postoperative period was uneventful. Microscopic examination of the dura with an attached predominantly circumscribed neoplasm with areas of invasion into adjacent brain parenchyma was done. The neoplasm was predominantly composed of small round cells in sheets, with scanty cytoplasm and vesicular mildly pleomorphic nuclei with low mitotic activity [Figure 1b]. Focal areas of increased cellularity containing plump spindle‑shaped cells with brisk mitotic activity were seen [Figure 1c]. With a differential diagnosis between a PNET and gliosarcoma, immunohistochemistry was done to characterize the neoplasm. Tumor cells were negative for synaptophysin, chromogranin, glial fibrillary acidic protein (GFAP), cytokeratin, leucocyte common antigen (LCA), epithelial membrane antigen (EMA), and desmin while showing diffuse strong positivity for vimentin and S‑100. Tumour cells showed strong membranous immunoreactivity for CD 99 antigen (using Dako Monoclonal Mouse Anti‑Human MIC‑2, clone Neurology India | Jul-Aug 2014 | Vol 62 | Issue 4
[Downloaded free from http://www.neurologyindia.com on Thursday, September 25, 2014, IP: 202.177.173.189] || Click here to download free Android application fo this journal Amita, et al.: Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor
a
b
c Figure 1: (a) MRI brain shows a well-defined enhancing lesion in right frontal region with mass effect and adjoining meningeal enhancement, (b) Microscopy shows a small round cells neoplasm, and (b) Cellular areas with brisk mitotic activity. (b and c H and E, x100)
12E7 with identical reactivity as monoclonal antibodies HBA‑71 and RFB‑1). Reticulin stain showed a pericellular pattern. Most tumor cells showed periodic acid‑Schiff– positive, diastase‑sensitive material consistent with glycogen in the cytoplasm [Figure 2]. With a diagnosis of ES/pPNET involving dura and frontal lobe, WHO grade IV, the patient was started on chemotherapy with ifosfamide, adriamycin, and etoptoside and is doing well after four cycles.
Discussion The ES family of tumors most commonly involves the bone and soft tissue.[2] Primary intracranial ES/pPNET is a recently recognized entity of CNS PNET. There are less than 15 case reports of this entity in the literature.[3‑5] The diagnosis is based on correlating small round cell tumor histology with cytoplasmic glycogen positivity and immunohistochemistry showing positivity for MIC‑2 antigen and negativity for LCA, EMA, cytokeratin and desmin, and with characteristic translocation. The detection of p30/32 cell surface antigen (also known as the MIC2 gene product, which can be detected by antibodies such as HBA71 and O13) and reciprocal translocation (11;22) (q24;q12) are characteristic of this family of tumors.[2,4] The MIC2 gene product (CD99), present in nearly all ES/pPNET, is also detected in other small blue round cell tumors such as neuroblastoma, lymphoma, and rhabdomyosarcomas, where cells show cytoplasmic positivity. Distinct membrane staining is typical of ES/pPNET. Central PNETs are reported to be negative for CD99 staining.[3] Reports in literature indicate two patterns of meningeal involvement. [3] One characterized by a diffuse involvement of the cranial and spinal leptomeninges in Neurology India | Jul-Aug 2014 | Vol 62 | Issue 4
a
b
c
d
Figure 2: (a) Pericellular reticulin pattern, (b) Cytoplasmic Periodic-acid Schiff positivity, (c) Positive S100 staining and (d) membranous staining with CD99 (MIC-2)
the absence of a primary intraparenchymal or meningeal tumor and the other characterized by a localized dural‑based mass mimicking meningioma, as seen in our case. It is clinically important to distinguish ES/pPNET and central PNET as the treatment protocols and prognosis differ.[5] ES/pPNET has a long‑term disease‑free survival, which is uncommon in central PNET. These are relatively well‑circumscribed tumors, allowing gross total resection and their sensitivity to chemotherapy probably contributes for the better prognosis.[3] Awareness of this entity and differentiating it from the more common central PNET is important for the pathologist to help in guiding treatment.
References 1. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO Classification of tumours of the central nervous system. Vol. 4. Lyon, France: IARC; 2007. p. 141‑6. 2. Amita RN, Sandhyamani S, Balasubramoniam KR. Primary primitive neuroectodermal tumor of lung: A case report. Indian J Pathol Microbiol 2013;56:479‑80. 3. Dedeurwaerdere F, Giannini C, Sciot R, Rubin BP, Perilongo G, Borghi L, et al. Primary peripheral PNET/Ewing’ sarcoma of the dura: A clinicopathologic entity distinct from central PNET. Mod Pathol 2002;15;673‑8. 4. Pekala JS, Gururangan S, Provenzale JM, Mukundan S Jr. Central nervous system extraosseous Ewing sarcoma: Radiologic manifestations of this newly defined pathological entity. AJNR Am J Neuroradiol 2006;27:580‑3. 5. Bano S, Yadav SN, Garga UC. Case Report: Intracranial peripheral primitive neuroectodermal tumor – Ewing’s sarcoma of dura with transcalvarial–subgaleal extension: An unusual radiological presentation. Indian J Radiol Imaging 2009;19:305‑7. How to cite this article: Amita R, Sandhyamani S, Nair S, Kapilamoorthy TR. Intracranial Ewings Sarcoma/peripheral primitive neuroectodermal tumor. Neurol India 2014;62:426-7. Source of Support: Nill, Conflict of Interest: None declared.
427
Copyright of Neurology India is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
