Skip to main content
Top
Published in: Child's Nervous System 3/2019

01-03-2019 | Case Report

Intracranial Ewing sarcoma with whole genome study

Authors: Jeemin Yim, Woo Seung Lee, Seung Ki Kim, Hyoung Jin Kang, Jeongmo Bae, Sung-Hye Park

Published in: Child's Nervous System | Issue 3/2019

Login to get access

Abstract

Introduction

Ewing sarcoma (ES) as a primary intracranial tumor is very rare. Recently, CNS embryonal tumors with ES-like genomic change have been reported. Patients and methods We report a case of intracranial Ewing sarcoma in a 13-year-old girl who complained of headache and migraine. The tumor had developed in the right middle cranial fossa with a mass effect on the brain with impending transuncal herniation.

Results

Undifferentiated small round cell morphology with completely negative results for friend leukemia integration 1 transcription factor (Fli-1) and a nonspecific cytoplasmic CD99-positive staining pattern mislead the diagnosis as central nervous system (CNS) embryonal tumor, NOS. However, whole genome sequencing (WGS) revealed Ewing sarcoma (EWS)-Fli-1 gene fusion, which was confirmed by fluorescence in situ hybridization study and the diagnosis was revised to ES.

Conclusions

This case is a true intracranial but extra-axial ES confirmed by WGS. We report this case of intracranial ES to demonstrate the importance of marker gene studies using FISH or NGS.
Literature
1.
go back to reference Maire G, Brown CW, Bayani J, Pereira C, Gravel DH, Bell JC, Zielenska M, Squire JA (2008) Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversion-insertion mechanism of EWS-ERG fusion gene formation: a case analysis and literature review. Cancer Genet Cytogenet 181:81–92CrossRefPubMed Maire G, Brown CW, Bayani J, Pereira C, Gravel DH, Bell JC, Zielenska M, Squire JA (2008) Complex rearrangement of chromosomes 19, 21, and 22 in Ewing sarcoma involving a novel reciprocal inversion-insertion mechanism of EWS-ERG fusion gene formation: a case analysis and literature review. Cancer Genet Cytogenet 181:81–92CrossRefPubMed
2.
go back to reference Charville GW, Wang WL, Ingram DR, Roy A, Thomas D, Patel RM, Hornick JL, van de Rijn M, Lazar AJ (2017) EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma. Mod Pathol 30:1312–1320CrossRefPubMed Charville GW, Wang WL, Ingram DR, Roy A, Thomas D, Patel RM, Hornick JL, van de Rijn M, Lazar AJ (2017) EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma. Mod Pathol 30:1312–1320CrossRefPubMed
3.
go back to reference Smith SC, Palanisamy N, Martin E, Almenara J, McHugh JB, Choi EK, Lucas DR, Betz BL, Thomas D, Patel RM (2017) The utility of ETV1, ETV4 and ETV5 RNA in-situ hybridization in the diagnosis of CIC-DUX sarcomas. Histopathology 70:657–663CrossRefPubMed Smith SC, Palanisamy N, Martin E, Almenara J, McHugh JB, Choi EK, Lucas DR, Betz BL, Thomas D, Patel RM (2017) The utility of ETV1, ETV4 and ETV5 RNA in-situ hybridization in the diagnosis of CIC-DUX sarcomas. Histopathology 70:657–663CrossRefPubMed
4.
go back to reference Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Lastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lotsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Fruhwald MC, Milde T, Hasselblatt M, Wesseling P, Rossler J, Schuller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072CrossRefPubMedPubMedCentral Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DTW, Capper D, Sill M, Buchhalter I, Northcott PA, Leis I, Ryzhova M, Koelsche C, Pfaff E, Allen SJ, Balasubramanian G, Worst BC, Pajtler KW, Brabetz S, Johann PD, Sahm F, Reimand J, Mackay A, Carvalho DM, Remke M, Phillips JJ, Perry A, Cowdrey C, Drissi R, Fouladi M, Giangaspero F, Lastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lotsch D, Berger W, Slavc I, Haberler C, Jouvet A, Holm S, Hofer S, Prinz M, Keohane C, Fried I, Mawrin C, Scheie D, Mobley BC, Schniederjan MJ, Santi M, Buccoliero AM, Dahiya S, Kramm CM, von Bueren AO, von Hoff K, Rutkowski S, Herold-Mende C, Fruhwald MC, Milde T, Hasselblatt M, Wesseling P, Rossler J, Schuller U, Ebinger M, Schittenhelm J, Frank S, Grobholz R, Vajtai I, Hans V, Schneppenheim R, Zitterbart K, Collins VP, Aronica E, Varlet P, Puget S, Dufour C, Grill J, Figarella-Branger D, Wolter M, Schuhmann MU, Shalaby T, Grotzer M, van Meter T, Monoranu CM, Felsberg J, Reifenberger G, Snuderl M, Forrester LA, Koster J, Versteeg R, Volckmann R, van Sluis P, Wolf S, Mikkelsen T, Gajjar A, Aldape K, Moore AS, Taylor MD, Jones C, Jabado N, Karajannis MA, Eils R, Schlesner M, Lichter P, von Deimling A, Pfister SM, Ellison DW, Korshunov A, Kool M (2016) New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell 164:1060–1072CrossRefPubMedPubMedCentral
5.
go back to reference Tanboon J, Sitthinamsuwan B, Paruang T, Marrano P, Thorner PS (2012) Primary intracranial Ewing sarcoma with an unusually aggressive course: a case report and review of the literature. Neuropathology 32:293–300CrossRefPubMed Tanboon J, Sitthinamsuwan B, Paruang T, Marrano P, Thorner PS (2012) Primary intracranial Ewing sarcoma with an unusually aggressive course: a case report and review of the literature. Neuropathology 32:293–300CrossRefPubMed
6.
go back to reference Chebib I, Jo VY (2016) Round cell sarcoma with CIC-DUX4 gene fusion: discussion of the distinctive cytomorphologic, immunohistochemical, and molecular features in the differential diagnosis of round cell tumors. Cancer Cytopathol 124:350–361CrossRefPubMed Chebib I, Jo VY (2016) Round cell sarcoma with CIC-DUX4 gene fusion: discussion of the distinctive cytomorphologic, immunohistochemical, and molecular features in the differential diagnosis of round cell tumors. Cancer Cytopathol 124:350–361CrossRefPubMed
7.
go back to reference Picarsic J, Reyes-Mugica M (2015) Phenotype and immunophenotype of the most common pediatric tumors. Appl Immunohistochem Mol Morphol 23:313–326CrossRefPubMed Picarsic J, Reyes-Mugica M (2015) Phenotype and immunophenotype of the most common pediatric tumors. Appl Immunohistochem Mol Morphol 23:313–326CrossRefPubMed
8.
go back to reference Antonelli M, Caltabiano R, Chiappetta C, Oliva MA, Giangaspero F, Lanzafame S (2011) Primary peripheral PNET/Ewing’s sarcoma arising in the meninges, confirmed by the presence of the rare translocation t(21;22) (q22;q12). Neuropathology 31:549–555CrossRefPubMed Antonelli M, Caltabiano R, Chiappetta C, Oliva MA, Giangaspero F, Lanzafame S (2011) Primary peripheral PNET/Ewing’s sarcoma arising in the meninges, confirmed by the presence of the rare translocation t(21;22) (q22;q12). Neuropathology 31:549–555CrossRefPubMed
9.
go back to reference Kleinschmidt-DeMasters BK, Lovell MA, Donson AM, Wilkinson CC, Madden JR, Addo-Yobo SO, Lillehei KO, Foreman NK (2007) Molecular array analyses of 51 pediatric tumors shows overlap between malignant intracranial ectomesenchymoma and MPNST but not medulloblastoma or atypical teratoid rhabdoid tumor. Acta Neuropathol 113:695–703CrossRefPubMed Kleinschmidt-DeMasters BK, Lovell MA, Donson AM, Wilkinson CC, Madden JR, Addo-Yobo SO, Lillehei KO, Foreman NK (2007) Molecular array analyses of 51 pediatric tumors shows overlap between malignant intracranial ectomesenchymoma and MPNST but not medulloblastoma or atypical teratoid rhabdoid tumor. Acta Neuropathol 113:695–703CrossRefPubMed
10.
go back to reference Mobley BC, Roulston D, Shah GV, Bijwaard KE, McKeever PE (2006) Peripheral primitive neuroectodermal tumor/Ewing’s sarcoma of the craniospinal vault: case reports and review. Hum Pathol 37:845–853CrossRefPubMed Mobley BC, Roulston D, Shah GV, Bijwaard KE, McKeever PE (2006) Peripheral primitive neuroectodermal tumor/Ewing’s sarcoma of the craniospinal vault: case reports and review. Hum Pathol 37:845–853CrossRefPubMed
11.
go back to reference Mazur MA, Gururangan S, Bridge JA, Cummings TJ, Mukundan S, Fuchs H, Larrier N, Halperin EC (2005) Intracranial Ewing sarcoma. Pediatr Blood Cancer 45:850–856CrossRefPubMed Mazur MA, Gururangan S, Bridge JA, Cummings TJ, Mukundan S, Fuchs H, Larrier N, Halperin EC (2005) Intracranial Ewing sarcoma. Pediatr Blood Cancer 45:850–856CrossRefPubMed
12.
go back to reference Tison V, Cerasoli S, Morigi F, Ladanyi M, Gerald WL, Rosai J (1996) Intracranial desmoplastic small-cell tumor. Report of a case. Am J Surg Pathol 20:112–117CrossRefPubMed Tison V, Cerasoli S, Morigi F, Ladanyi M, Gerald WL, Rosai J (1996) Intracranial desmoplastic small-cell tumor. Report of a case. Am J Surg Pathol 20:112–117CrossRefPubMed
13.
go back to reference Cherif El Asri A, Benzagmout M, Chakour K, Chaoui MF, Laaguili J, Chahdi H, Gazzaz M, El Mostarchid B (2018) Primary intracranial pPNET/Ewing sarcoma: diagnosis, management, and prognostic factors dilemma-a systematic review of the literature. World Neurosurg 115:346–356CrossRefPubMed Cherif El Asri A, Benzagmout M, Chakour K, Chaoui MF, Laaguili J, Chahdi H, Gazzaz M, El Mostarchid B (2018) Primary intracranial pPNET/Ewing sarcoma: diagnosis, management, and prognostic factors dilemma-a systematic review of the literature. World Neurosurg 115:346–356CrossRefPubMed
14.
go back to reference Torchia EC, Jaishankar S, Baker SJ (2003) Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells. Cancer Res 63:3464–3468PubMed Torchia EC, Jaishankar S, Baker SJ (2003) Ewing tumor fusion proteins block the differentiation of pluripotent marrow stromal cells. Cancer Res 63:3464–3468PubMed
Metadata
Title
Intracranial Ewing sarcoma with whole genome study
Authors
Jeemin Yim
Woo Seung Lee
Seung Ki Kim
Hyoung Jin Kang
Jeongmo Bae
Sung-Hye Park
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Child's Nervous System / Issue 3/2019
Print ISSN: 0256-7040
Electronic ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-018-3997-1

Other articles of this Issue 3/2019

Child's Nervous System 3/2019 Go to the issue