Advertisement

Current Oncology Reports

, 20:69 | Cite as

Molecular Classification and Management of Rare Pediatric Embryonal Brain Tumors

  • Patrick Sin-Chan
  • Bryan K. Li
  • Ben Ho
  • Adriana Fonseca
  • Annie Huang
Pediatric Oncology (G Tian, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Pediatric Oncology

Abstract

Purpose of Review

Malignant embryonal brain tumors (EBTs) of childhood span a wide clinical spectrum but can share remarkably similar morphologic features. This overlap presents significant diagnostic challenges, particularly for tumor entities that are rarely encountered in clinical practice and for which diagnostic criteria were poorly defined. This review will provide an update on the evolving characterization and treatment of rare EBTs.

Recent Findings

Rapid advances in genomic tools have led to the discovery of robust molecular markers, and identification of novel tumor types and subtypes for almost all major categories of pediatric brain tumors. These developments have had significant impact on improving the diagnostic classification of the rare EBTs, particularly for tumors with newly recognized C19MC alterations, central nervous system primitive neuroectodermal tumors (CNS-PNET), and pineoblastoma (PB).

Summary

These important developments in the clinical and molecular understanding of rare EBTs are paving the way for novel therapeutic strategies and improved clinical management.

Keywords

Brain tumor Cancer CNS-PNET PNET C19MC ETMR ETANTR Ependymoblastoma Medulloepithelioma Pineoblastoma Pediatrics Therapeutics 

Notes

Compliance with Ethical Standards

Conflict of Interest

Patrick Sin-Chan was an employee of Regeneron Pharmaceuticals at the time this article was written.

Bryan K. Li declares that he has no conflict of interest.

Ben Ho declares that he has no conflict of interest.

Adriana Fonseca declares that she has no conflict of interest.

Annie Huang declares that she has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major Importance

  1. 1.
    Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–20.  https://doi.org/10.1007/s00401-016-1545-1.CrossRefPubMedGoogle Scholar
  2. 2.
    SEER*Stat Database: Incidence - SEER 18 Regs Research Data + Hurricane Katrina impacted Louisiana cases, Nov 2016 Sub (1973–2014 varying) - linked to county attributes—total U.S., 1969–2015 counties, National Cancer Institute, DCCPS, Surveillance Research Program [database on the Internet]2017. Available from: www.seer.cancer.gov. Accessed:
  3. 3.
    Rorke LB, Packer RJ, Biegel JA. Central nervous system atypical teratoid/rhabdoid tumors of infancy and childhood: definition of an entity. J Neurosurg. 1996;85(1):56–65.  https://doi.org/10.3171/jns.1996.85.1.0056.CrossRefPubMedGoogle Scholar
  4. 4.
    Biegel JA, Zhou JY, Rorke LB, Stenstrom C, Wainwright LM, Fogelgren B. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res. 1999;59(1):74–9.PubMedGoogle Scholar
  5. 5.
    Pomeroy SL, Tamayo P, Gaasenbeek M, Sturla LM, Angelo M, McLaughlin ME, et al. Prediction of central nervous system embryonal tumour outcome based on gene expression. Nature. 2002;415(6870):436–42.  https://doi.org/10.1038/415436a.CrossRefPubMedGoogle Scholar
  6. 6.
    Li M, Lee KF, Lu Y, Clarke I, Shih D, Eberhart C, et al. Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors. Cancer Cell. 2009;16(6):533–46.  https://doi.org/10.1016/j.ccr.2009.10.025.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Picard D, Miller S, Hawkins CE, Bouffet E, Rogers HA, Chan TS, et al. Markers of survival and metastatic potential in childhood CNS primitive neuro-ectodermal brain tumours: an integrative genomic analysis. Lancet Oncol. 2012;13(8):838–48.  https://doi.org/10.1016/S1470-2045(12)70257-7.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    •• Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DT, Capper D, et al. New brain tumor entities emerge from molecular classification of CNS-PNETs. Cell. 2016;164(5):1060–72.  https://doi.org/10.1016/j.cell.2016.01.015. Identified new CNS-PNET molecular entities. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Eberhart CG, Brat DJ, Cohen KJ, Burger PC. Pediatric neuroblastic brain tumors containing abundant neuropil and true rosettes. Pediatr Dev Pathol. 2000;3(4):346–52.CrossRefPubMedGoogle Scholar
  10. 10.
    Pfister S, Remke M, Castoldi M, Bai AH, Muckenthaler MU, Kulozik A, et al. Novel genomic amplification targeting the microRNA cluster at 19q13.42 in a pediatric embryonal tumor with abundant neuropil and true rosettes. Acta Neuropathol. 2009;117(4):457–64.  https://doi.org/10.1007/s00401-008-0467-y.CrossRefPubMedGoogle Scholar
  11. 11.
    •• Spence T, Sin-Chan P, Picard D, Barszczyk M, Hoss K, Lu M, et al. CNS-PNETs with C19MC amplification and/or LIN28 expression comprise a distinct histogenetic diagnostic and therapeutic entity. Acta Neuropathol. 2014;128(2):291–303.  https://doi.org/10.1007/s00401-014-1291-1. Identified DNMT and HDAC inhibitors as rational therapeutics in ETMR. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Korshunov A, Sturm D, Ryzhova M, Hovestadt V, Gessi M, Jones DT, et al. Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity. Acta Neuropathol. 2014;128(2):279–89.  https://doi.org/10.1007/s00401-013-1228-0.CrossRefPubMedGoogle Scholar
  13. 13.
    Korshunov A, Jakobiec FA, Eberhart CG, Hovestadt V, Capper D, Jones DT, et al. Comparative integrated molecular analysis of intraocular medulloepitheliomas and central nervous system embryonal tumors with multilayered rosettes confirms that they are distinct nosologic entities. Neuropathology. 2015;35:538–44.  https://doi.org/10.1111/neup.12227.CrossRefPubMedGoogle Scholar
  14. 14.
    • Kleinman CL, Gerges N, Papillon-Cavanagh S, Sin-Chan P, Pramatarova A, Quang DA, et al. Fusion of TTYH1 with the C19MC microRNA cluster drives expression of a brain-specific DNMT3B isoform in the embryonal brain tumor ETMR. Nat Genet. 2014;46(1):39–44.  https://doi.org/10.1038/ng.2849. Demonstrated TTYH1-C19MC fusion drives overexpression of C19MC which inhibit RBL2 to activate an embryonic DNMT3B isoform. CrossRefPubMedGoogle Scholar
  15. 15.
    von Hoff K, Pizer, Barry, Dufour, Christelle, van Vuurden et al. MB-079: prognostic factors in childhood CNS-PNET and pineoblastoma: an international meta-analysis of original clinical data. Neuro-Oncology 2014;Volume 16(Supplemental issue 1):i71–i96.Google Scholar
  16. 16.
    Horwitz M, Dufour C, Leblond P, Bourdeaut F, Faure-Conter C, Bertozzi AI, et al. Embryonal tumors with multilayered rosettes in children: the SFCE experience. Childs Nerv Syst. 2016;32(2):299–305.  https://doi.org/10.1007/s00381-015-2920-2.CrossRefPubMedGoogle Scholar
  17. 17.
    Hansford J, Dodgshun A, Wells O, Huang A, Gottardo NC. PNR-40: embryonal tumor with multilayered rosettes: a unique new clinical entity. Neuro-Oncology. 2016;18(Supplement_3):iii15.2–ii15.CrossRefGoogle Scholar
  18. 18.
    Schmidt C, Schubert NA, Brabetz S, Mack N, Schwalm B, Chan JA, et al. Pre-clinical drug screen reveals topotecan, actinomycin D and volasertib as potential new therapeutic candidates for ETMR brain tumor patients. Neuro-Oncology. 2017;19:1607–17.  https://doi.org/10.1093/neuonc/nox093.CrossRefPubMedGoogle Scholar
  19. 19.
    Spence T, Perotti C, Sin-Chan P, Picard D, Wu W, Singh A, et al. A novel C19MC amplified cell line links Lin28/let-7 to mTOR signaling in embryonal tumor with multilayered rosettes. Neuro-Oncology. 2014;16(1):62–71.  https://doi.org/10.1093/neuonc/not162.CrossRefPubMedGoogle Scholar
  20. 20.
    Sin-Chan P, Huang A. DNMTs as potential therapeutic targets in high-risk pediatric embryonal brain tumors. Expert Opin Ther Targets. 2014;18(10):1103–7.  https://doi.org/10.1517/14728222.2014.938052.CrossRefPubMedGoogle Scholar
  21. 21.
    Neumann JE, Wefers AK, Lambo S, Bianchi E, Bockstaller M, Dorostkar MM, et al. A mouse model for embryonal tumors with multilayered rosettes uncovers the therapeutic potential of Sonic-hedgehog inhibitors. Nat Med. 2017;23(10):1191–202.  https://doi.org/10.1038/nm.4402.CrossRefPubMedGoogle Scholar
  22. 22.
    Timmermann B, Kortmann RD, Kuhl J, Meisner C, Dieckmann K, Pietsch T, et al. Role of radiotherapy in the treatment of supratentorial primitive neuroectodermal tumors in childhood: results of the prospective German brain tumor trials HIT 88/89 and 91. J Clin Oncol : Off J Am Soc Clin Oncol. 2002;20(3):842–9.CrossRefGoogle Scholar
  23. 23.
    Timmermann B, Kortmann RD, Kuhl J, Rutkowski S, Meisner C, Pietsch T, et al. Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials. J Clin Oncol : Off J Am Soc Clin Oncol. 2006;24(10):1554–60.  https://doi.org/10.1200/JCO.2005.04.8074.CrossRefGoogle Scholar
  24. 24.
    Jakacki RI. Pineal and nonpineal supratentorial primitive neuroectodermal tumors. Childs Nerv Syst. 1999;15(10):586–91.  https://doi.org/10.1007/s003810050547.CrossRefPubMedGoogle Scholar
  25. 25.
    Burger PC. Supratentorial primitive neuroectodermal tumor (sPNET). Brain Pathol. 2006;16(1):86.CrossRefPubMedGoogle Scholar
  26. 26.
    McCabe MG, Ichimura K, Liu L, Plant K, Backlund LM, Pearson DM, et al. High-resolution array-based comparative genomic hybridization of medulloblastomas and supratentorial primitive neuroectodermal tumors. J Neuropathol Exp Neurol. 2006;65(6):549–61.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Pfister S, Remke M, Toedt G, Werft W, Benner A, Mendrzyk F, et al. Supratentorial primitive neuroectodermal tumors of the central nervous system frequently harbor deletions of the CDKN2A locus and other genomic aberrations distinct from medulloblastomas. Genes, Chromosomes & Cancer. 2007;46(9):839–51.  https://doi.org/10.1002/gcc.20471.CrossRefGoogle Scholar
  28. 28.
    Li MH, Bouffet E, Hawkins CE, Squire JA, Huang A. Molecular genetics of supratentorial primitive neuroectodermal tumors and pineoblastoma. Neurosurg Focus. 2005;19(5):E3.CrossRefPubMedGoogle Scholar
  29. 29.
    Miller S, Rogers HA, Lyon P, Rand V, Adamowicz-Brice M, Clifford SC, et al. Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro-Oncology. 2011;13(8):866–79.  https://doi.org/10.1093/neuonc/nor070.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Inda MM, Perot C, Guillaud-Bataille M, Danglot G, Rey JA, Bello MJ, et al. Genetic heterogeneity in supratentorial and infratentorial primitive neuroectodermal tumours of the central nervous system. Histopathology. 2005;47(6):631–7.  https://doi.org/10.1111/j.1365-2559.2005.02304.x.CrossRefPubMedGoogle Scholar
  31. 31.
    Modzelewska K, Boer EF, Mosbruger TL, Picard D, Anderson D, Miles RR, et al. MEK inhibitors reverse growth of embryonal brain tumors derived from oligoneural precursor cells. Cell Rep. 2016;17(5):1255–64.  https://doi.org/10.1016/j.celrep.2016.09.081.CrossRefPubMedGoogle Scholar
  32. 32.
    Ho B, Huang A. Unpublished work. 2018.Google Scholar
  33. 33.
    Ueno-Yokohata H, Okita H, Nakasato K, Akimoto S, Hata J, Koshinaga T, et al. Consistent in-frame internal tandem duplications of BCOR characterize clear cell sarcoma of the kidney. Nat Genet. 2015;47(8):861–3.  https://doi.org/10.1038/ng.3338.CrossRefPubMedGoogle Scholar
  34. 34.
    Roy A, Kumar V, Zorman B, Fang E, Haines KM, Doddapaneni H, et al. Recurrent internal tandem duplications of BCOR in clear cell sarcoma of the kidney. Nat Commun. 2015;6:8891.  https://doi.org/10.1038/ncomms9891.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Haidar A, Arekapudi S, DeMattia F, Abu-Isa E, Kraut M. High-grade undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: emerging entities of soft tissue tumors with unique histopathologic features--a case report and literature review. Am J Case Rep. 2015;16:87–94.  https://doi.org/10.12659/AJCR.892551.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Graham C, Chilton-MacNeill S, Zielenska M, Somers GR. The CIC-DUX4 fusion transcript is present in a subgroup of pediatric primitive round cell sarcomas. Hum Pathol. 2012;43(2):180–9.  https://doi.org/10.1016/j.humpath.2011.04.023.CrossRefPubMedGoogle Scholar
  37. 37.
    Hirose T, Nobusawa S, Sugiyama K, Amatya VJ, Fujimoto N, Sasaki A, et al. Astroblastoma: a distinct tumor entity characterized by alterations of the X chromosome and MN1 rearrangement. Brain Pathol. 2017;  https://doi.org/10.1111/bpa.12565.
  38. 38.
    Wood MD, Tihan T, Perry A, Chacko G, Turner C, Pu C, et al. Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities. Brain Pathol. 2017;28:192–202.  https://doi.org/10.1111/bpa.12561.CrossRefPubMedGoogle Scholar
  39. 39.
    Jakacki RI, Burger PC, Kocak M, Boyett JM, Goldwein J, Mehta M, et al. Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: a report from the Children’s Oncology Group. Pediatr Blood Cancer. 2015;62(5):776–83.  https://doi.org/10.1002/pbc.25405.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Dirks PB, Harris L, Hoffman HJ, Humphreys RP, Drake JM, Rutka JT. Supratentorial primitive neuroectodermal tumors in children. J Neuro-Oncol. 1996;29(1):75–84.CrossRefGoogle Scholar
  41. 41.
    Cohen BH, Zeltzer PM, Boyett JM, Geyer JR, Allen JC, Finlay JL, et al. Prognostic factors and treatment results for supratentorial primitive neuroectodermal tumors in children using radiation and chemotherapy: a Childrens Cancer Group randomized trial. J Clin Oncol : Off J Am Soc Clin Oncol. 1995;13(7):1687–96.CrossRefGoogle Scholar
  42. 42.
    Johnston DL, Keene DL, Lafay-Cousin L, Steinbok P, Sung L, Carret AS, et al. Supratentorial primitive neuroectodermal tumors: a Canadian pediatric brain tumor consortium report. J Neuro-Oncol. 2008;86(1):101–8.  https://doi.org/10.1007/s11060-007-9440-1.CrossRefGoogle Scholar
  43. 43.
    Albright AL, Wisoff JH, Zeltzer P, Boyett J, Rorke LB, Stanley P, et al. Prognostic factors in children with supratentorial (nonpineal) primitive neuroectodermal tumors. A neurosurgical perspective from the Children's Cancer Group. Pediatr Neurosurg. 1995;22(1):1–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Pizer BL, Weston CL, Robinson KJ, Ellison DW, Ironside J, Saran F, et al. Analysis of patients with supratentorial primitive neuro-ectodermal tumours entered into the SIOP/UKCCSG PNET 3 study. Eur J Cancer. 2006;42(8):1120–8.  https://doi.org/10.1016/j.ejca.2006.01.039.CrossRefPubMedGoogle Scholar
  45. 45.
    Chintagumpala M, Hassall T, Palmer S, Ashley D, Wallace D, Kasow K, et al. A pilot study of risk-adapted radiotherapy and chemotherapy in patients with supratentorial PNET. Neuro-Oncology. 2009;11(1):33–40.  https://doi.org/10.1215/15228517-2008-079.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Geyer JR, Sposto R, Jennings M, Boyett JM, Axtell RA, Breiger D, et al. Multiagent chemotherapy and deferred radiotherapy in infants with malignant brain tumors: a report from the Children’s Cancer Group. J Clin Oncol : Off J Am Soc Clin Oncol. 2005;23(30):7621–31.  https://doi.org/10.1200/JCO.2005.09.095.CrossRefGoogle Scholar
  47. 47.
    Strother DR, Lafay-Cousin L, Boyett JM, Burger P, Aronin P, Constine L, et al. Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34. Neuro-Oncology. 2014;16(3):457–65.  https://doi.org/10.1093/neuonc/not163.CrossRefPubMedGoogle Scholar
  48. 48.
    Hwang E, Kool M, Burger P, Capper D, Chavez L, Brabetz S, et al. Molecular diagnostics reveal 60% higher survival for molecularly-verified versus histopathologically-diagnosed pediatric supratentorial central nervous system embryonal tumors and pineoblastomas; a report from the Children’s Oncology Group ACNS0332 trial. Neuro-Oncology. 2017;19:vi184–5.CrossRefGoogle Scholar
  49. 49.
    Cohen BH, Geyer JR, Miller DC, Curran JG, Zhou T, Holmes E, et al. Pilot study of intensive chemotherapy with peripheral hematopoietic cell support for children less than 3 years of age with malignant brain tumors, the CCG-99703 phase I/II study. A report from the Children’s Oncology Group. Pediatr Neurol. 2015;53(1):31–46.  https://doi.org/10.1016/j.pediatrneurol.2015.03.019.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Jouvet A, Vasiljevic A, Nakazato Y, Tanaka S. Tumours of the pineal region. In: Louis D, editor. WHO classification of tumours of the central nervous system. 4 ed.: International Agency for Research on Cancer; 2016. p. 170–82.Google Scholar
  51. 51.
    Russo C, Pellarin M, Tingby O, Bollen AW, Lamborn KR, Mohapatra G, et al. Comparative genomic hybridization in patients with supratentorial and infratentorial primitive neuroectodermal tumors. Cancer. 1999;86(2):331–9.CrossRefPubMedGoogle Scholar
  52. 52.
    Tate M, Sughrue ME, Rutkowski MJ, Kane AJ, Aranda D, McClinton L, et al. The long-term postsurgical prognosis of patients with pineoblastoma. Cancer. 2012;118(1):173–9.  https://doi.org/10.1002/cncr.26300.CrossRefPubMedGoogle Scholar
  53. 53.
    Jouvet A, Saint-Pierre G, Fauchon F, Privat K, Bouffet E, Ruchoux MM, et al. Pineal parenchymal tumors: a correlation of histological features with prognosis in 66 cases. Brain Pathol. 2000;10(1):49–60.CrossRefPubMedGoogle Scholar
  54. 54.
    Friedrich C, von Bueren AO, von Hoff K, Gerber NU, Ottensmeier H, Deinlein F, et al. Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy. Neuro-Oncology. 2013;15(2):224–34.  https://doi.org/10.1093/neuonc/nos292.CrossRefPubMedGoogle Scholar
  55. 55.
    Fonseca A, Al-Karmi S, Vasiljevic A, Sin Chan P, Lafay Cousin L, Hansford J et al. Rare embryonal brain tumours. In: Gajjar A, editor. Brain tumors in children [in print]. 2017.Google Scholar
  56. 56.
    Lee JY, Wakabayashi T, Yoshida J. Management and survival of pineoblastoma: an analysis of 34 adults from the brain tumor registry of Japan. Neurol Med Chir (Tokyo) 2005;45(3):132–141; discussion 41–2.Google Scholar
  57. 57.
    Cuccia V, Rodríguez F, Palma F, Zuccaro G. Pinealoblastomas in children. Childs Nerv Syst. 2006;22(6):577–85.  https://doi.org/10.1007/s00381-006-0095-6.CrossRefPubMedGoogle Scholar
  58. 58.
    Farnia B, Allen PK, Brown PD, Khatua S, Levine NB, Li J, et al. Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single-institution retrospective review. World Neurosurg. 2014;82(6):1232–41.  https://doi.org/10.1016/j.wneu.2014.07.010.CrossRefPubMedGoogle Scholar
  59. 59.
    Chiechi MV, Smirniotopoulos JG, Mena H. Pineal parenchymal tumors: CT and MR features. J Comput Assist Tomogr. 1995;19(4):509–17.CrossRefPubMedGoogle Scholar
  60. 60.
    Nakamura M, Saeki N, Iwadate Y, Sunami K, Osato K, Yamaura A. Neuroradiological characteristics of pineocytoma and pineoblastoma. Neuroradiology. 2000;42(7):509–14.CrossRefPubMedGoogle Scholar
  61. 61.
    Smith AB, Rushing EJ, Smirniotopoulos JG. From the archives of the AFIP: lesions of the pineal region: radiologic-pathologic correlation. Radiographics. 2010;30(7):2001–20.  https://doi.org/10.1148/rg.307105131.CrossRefPubMedGoogle Scholar
  62. 62.
    Reis F, Faria AV, Zanardi VA, Menezes JR, Cendes F, Queiroz LS. Neuroimaging in pineal tumors. J Neuroimaging. 2006;16(1):52–8.  https://doi.org/10.1177/1051228405001514.CrossRefPubMedGoogle Scholar
  63. 63.
    Tien RD, Barkovich AJ, Edwards MS. MR imaging of pineal tumors. AJR Am J Roentgenol. 1990;155(1):143–51.  https://doi.org/10.2214/ajr.155.1.2162137.CrossRefPubMedGoogle Scholar
  64. 64.
    Parikh KA, Venable GT, Orr BA, Choudhri AF, Boop FA, Gajjar AJ, et al. Pineoblastoma-the experience at St. Jude Children’s Research Hospital. Neurosurgery. 2017;81(1):120–8.  https://doi.org/10.1093/neuros/nyx005.CrossRefPubMedGoogle Scholar
  65. 65.
    Miller S, Ward JH, Rogers HA, Lowe J, Grundy RG. Loss of INI1 protein expression defines a subgroup of aggressive central nervous system primitive neuroectodermal tumors. Brain Pathol. 2013;23(1):19–27.  https://doi.org/10.1111/j.1750-3639.2012.00610.x.CrossRefPubMedGoogle Scholar
  66. 66.
    de Jong MC, Kors WA, de Graaf P, Castelijns JA, Kivelä T, Moll AC. Trilateral retinoblastoma: a systematic review and meta-analysis. Lancet Oncol. 2014;15(10):1157–67.  https://doi.org/10.1016/s1470-2045(14)70336-5.CrossRefPubMedGoogle Scholar
  67. 67.
    de Kock L, Sabbaghian N, Druker H, Weber E, Hamel N, Miller S, et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014;128(4):583–95.  https://doi.org/10.1007/s00401-014-1318-7.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Brown AE, Leibundgut K, Niggli FK, Betts DR. Cytogenetics of pineoblastoma: four new cases and a literature review. Cancer Genet Cytogenet. 2006;170(2):175–9.  https://doi.org/10.1016/j.cancergencyto.2006.06.009.CrossRefPubMedGoogle Scholar
  69. 69.
    Rickert CH, Simon R, Bergmann M, Dockhorn-Dworniczak B, Paulus W. Comparative genomic hybridization in pineal parenchymal tumors. Genes, Chromosomes Cancer. 2001;30(1):99–104.CrossRefPubMedGoogle Scholar
  70. 70.
    Tsumanuma I, Sato M, Okazaki H, Tanaka R, Washiyama K, Kawasaki T, et al. The analysis of p53 tumor suppressor gene in pineal parenchymal tumors. Noshuyo Byori. 1995;12(1):39–43.PubMedGoogle Scholar
  71. 71.
    Tsumanuma I, Tanaka R, Abe S, Kawasaki T, Washiyama K, Kumanishi T. Infrequent mutation of Waf1/p21 gene, a CDK inhibitor gene, in brain tumors. Neurol Med Chir (Tokyo). 1997;37(2):150–6. discussion 6-7CrossRefGoogle Scholar
  72. 72.
    Fèvre-Montange M, Champier J, Szathmari A, Wierinckx A, Mottolese C, Guyotat J, et al. Microarray analysis reveals differential gene expression patterns in tumors of the pineal region. J Neuropathol Exp Neurol. 2006;65(7):675–84.  https://doi.org/10.1097/01.jnen.0000225907.90052.e3.CrossRefPubMedGoogle Scholar
  73. 73.
    Tate MC, Rutkowski MJ, Parsa AT. Contemporary management of pineoblastoma. Neurosurg Clin N Am. 2011;22(3):409–12, ix.  https://doi.org/10.1016/j.nec.2011.05.001.CrossRefPubMedGoogle Scholar
  74. 74.
    Fauchon F, Jouvet A, Paquis P, Saint-Pierre G, Mottolese C, Ben Hassel M, et al. Parenchymal pineal tumors: a clinicopathological study of 76 cases. Int J Radiat Oncol Biol Phys. 2000;46(4):959–68.CrossRefPubMedGoogle Scholar
  75. 75.
    Lutterbach J, Fauchon F, Schild SE, Chang SM, Pagenstecher A, Volk B, Ostertag C, Momm F, Jouvet A Malignant pineal parenchymal tumors in adult patients: patterns of care and prognostic factors. Neurosurgery 2002;51(1):44–55; discussion −6, 56.Google Scholar
  76. 76.
    Yamamoto I. Pineal region tumor: surgical anatomy and approach. J Neuro-Oncol. 2001;54(3):263–75.CrossRefGoogle Scholar
  77. 77.
    Duffner PK, Cohen ME, Sanford RA, Horowitz ME, Krischer JP, Burger PC, et al. Lack of efficacy of postoperative chemotherapy and delayed radiation in very young children with pineoblastoma. Pediatr Oncol Group Med Pediatric Oncol. 1995;25(1):38–44.CrossRefGoogle Scholar
  78. 78.
    Jakacki RI, Zeltzer PM, Boyett JM, Albright AL, Allen JC, Geyer JR, et al. Survival and prognostic factors following radiation and/or chemotherapy for primitive neuroectodermal tumors of the pineal region in infants and children: a report of the Childrens Cancer Group. J Clin Oncol. 1995;13(6):1377–83.CrossRefPubMedGoogle Scholar
  79. 79.
    Fangusaro JR, Jubran RF, Allen J, Gardner S, Dunkel IJ, Rosenblum M, et al. Brainstem primitive neuroectodermal tumors (bstPNET): results of treatment with intensive induction chemotherapy followed by consolidative chemotherapy with autologous hematopoietic cell rescue. Pediatr Blood Cancer. 2008;50(3):715–7.  https://doi.org/10.1002/pbc.21032.CrossRefPubMedGoogle Scholar
  80. 80.
    Gururangan S, McLaughlin C, Quinn J, Rich J, Reardon D, Halperin EC, et al. High-dose chemotherapy with autologous stem-cell rescue in children and adults with newly diagnosed pineoblastomas. J Clin Oncol. 2003;21(11):2187–91.  https://doi.org/10.1200/jco.2003.10.096.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Patrick Sin-Chan
    • 1
  • Bryan K. Li
    • 1
    • 2
  • Ben Ho
    • 1
  • Adriana Fonseca
    • 1
  • Annie Huang
    • 1
    • 2
  1. 1.Arthur and Sonia Labatt Brain Tumour Research Centre, Division of Haematology/OncologyHospital for Sick ChildrenTorontoCanada
  2. 2.Department of Laboratory Medicine and Pathobiology, Faculty of MedicineUniversity of TorontoTorontoCanada

Personalised recommendations