This paper was presented in abstract format at the International Society for Pediatric Neuro-oncology (06/12/2016, Liverpool, UK).
Michael J. Yang and Ros Whelan share equal contribution and authorship.
Ewing sarcoma typically arises in bone and is unrelated to intraparenchymal small blue cell embryonal central nervous system (CNS) tumors previously designated primitive neuroectodermal tumors (PNETs). When the CNS is impacted, it is usually secondary to local extension from either the epidural space, skull, or intracranial or spinal metastases. Primary examples within the cranial vault are rare, usually dural-based, and are largely case reports in the literature. We detail four pediatric patients with solitary, primary intracranial Ewing sarcoma, all manifesting the archetypal EWRS1 gene rearrangement that confirms diagnosis.
Neurosurgical Department records, spanning 21 years (1995–2016), were reviewed to identify patients. Demographics, clinical history, pathological/genetic features, and clinical course were retrieved from the medical record and personal files of the authors.
Four patients, one male and three females, age 5 to 16 years, were identified. One presented in extremis from a large lesion, two with soft tissue masses, and the fourth as an incidental finding after being involved in a motor vehicle collision. Three had clear bony involvement: a 10-year-old girl with a large left temporal lesion had clear origin in the skull, with spiculated calcified striations throughout the mass; a 9-year-old girl presented with a bony left petrous apex mass; and a 16-year-old girl presented with a left temporal mass with extension to the dura and underlying bone erosion. Only the 5-year-old boy had a large left frontoparietal mass traversing the falx with no bony contact. All four tumors manifested the diagnostic EWSR1 mutation and were treated with an Ewing sarcoma regimen. Outcomes were variable, with one patient showing progressive metastatic disease and death 3 years after presentation, one patient with disease-free survival 10.5 years after completion of therapy, and one alive and well at the completion of therapy 1 year after diagnosis. One patient completed therapy recently with post-therapy scans showing no evidence of disease.
Testing for the EWSR1 mutation confirms the diagnosis of Ewing sarcoma and excludes other types of embryonal CNS tumors. Long-term disease-free survival is possible with adherence to the appropriate therapeutic regimen after gross surgical resection.
Theeler BJ, Keylock J, Yoest S, Forouhar M (2009) Ewing’s sarcoma family tumors mimicking primary central nervous system neoplasms. J Neurol Sci 284(1-2):186–189. https://doi.org/10.1016/j.jns.2009.03.031 CrossRefPubMed
Balasubramaniam S, Nadkarni T, Menon R, Goel A, Rajashekaran P (2008) Primary Ewing’s sarcoma of the petroclival bone. J Clin Neurosci 15(6):712–714. https://doi.org/10.1016/j.jocn.2007.04.023 CrossRefPubMed
Cancer Facts & Figures 2016. American Cancer Society
Gurney J, Swensen A, Bulterys M: Malignant bone tumors. In: Cancer incidence and survival among children and adolescents: United States SEER program 1975-1995. NCI, SEER Program, 1999
Abrams MB, Bednarek KT, Bogoch S, Bogoch ES, Dardik HJ, Dowden R, Fox SC, Goins EE, Goodfried G, Herrman RA (1994) Early detection and monitoring of cancer with the anti-malignin antibody test. Cancer Detect Prev 18(1):65–78 PubMed
Harman SM, Gucciardo F, Heward CB et al (2005) Discrimination of breast cancer by anti-malignin antibody serum test in women undergoing biopsy. Cancer Epidemiol Biomark Prev 14(10):2310–2315. https://doi.org/10.1158/1055-9965.EPI-04-0802 CrossRef
Womer RB, West DC, Krailo MD, Dickman PS, Pawel BR, Grier HE, Marcus K, Sailer S, Healey JH, Dormans JP, Weiss AR (2012) Randomized controlled trial of interval-compressed chemotherapy for the treatment of localized Ewing sarcoma: a report from the Children’s oncology group. J Clin Oncol 30(33):4148–4154. https://doi.org/10.1200/JCO.2011.41.5703 CrossRefPubMedPubMedCentral
Steinbok P, Flodmark O, Norman M et al (1986) Primary Ewing’s sarcoma of the base of the skull. Neurosurgery 19(1):104–107. https://doi.org/10.1227/00006123-198607000-00016 CrossRefPubMed
Li Y, Tanaka K, Fan X, et al (2010) Inhibition of the transcriptional function of p53 by EWS-Fli1 chimeric protein in Ewing Family Tumors. Cancer Lett 294(1):57-65. https://doi.org/10.1016/j.canlet.2010.01.022 CrossRef
Janknecht R (2005) EWS-ETS oncoproteins: the linchpins of Ewing tumors. Gene 363:1–14. https://doi.org/10.1016/j.gene.2005.08.007 CrossRefPubMed
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(7):845–853. https://doi.org/10.1016/j.humpath.2006.02.011 CrossRefPubMed
Ahmad R, Mayol BR, Davis M, Rougraff BT (1999) Extraskeletal Ewing’s sarcoma. Cancer 85(3):725–731. https://doi.org/10.1002/(SICI)1097-0142(19990201)85:3<725::AID-CNCR23>3.0.CO;2-2 CrossRefPubMed
Rosen G, Caparros B, Nirenberg A, Marcove RC, Huvos AG, Kosloff C, Lane J, Murphy ML (1981) Ewing’s sarcoma: ten-year experience with adjuvant chemotherapy. Cancer 47(9):2204–2213. https://doi.org/10.1002/1097-0142(19810501)47:9<2204::AID-CNCR2820470916>3.0.CO;2-A CrossRefPubMed
Jain S, Kapoor G (2010) Chemotherapy in Ewing’s sarcoma. Indian J Orthopedics 44:369–377 CrossRef
Ahmed SA, Randall RL, DuBois SG et al (2017) Identification of patients with localized Ewing sarcoma at higher risk for local failure: a report from the Children’s Oncology Group. Int J Radiation Oncology: Biology Physics 99(5):1286–1294. https://doi.org/10.1016/j.ijrobp.2017.08.020 CrossRef
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131(6):803–820. https://doi.org/10.1007/s00401-016-1545-1 CrossRef
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, Łastowska M, Grajkowska W, Scheurlen W, Pietsch T, Hagel C, Gojo J, Lötsch 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, Frühwald MC, Milde T, Hasselblatt M, Wesseling P, Rößler J, Schüller 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(5):1060–1072. https://doi.org/10.1016/j.cell.2016.01.015 CrossRefPubMedPubMedCentral
- Intracranial Ewing sarcoma: four pediatric examples
Michael J. Yang
Jean M. Mulcahy Levy
B. K. Kleinschmidt-DeMasters
Todd C. Hankinson
Nicholas K. Foreman
Michael H. Handler
- Springer Berlin Heidelberg
Neu im Fachgebiet Chirurgie
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