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Child's Nervous System

, Volume 31, Issue 10, pp 1661–1676 | Cite as

Posterior fossa tumors in children: developmental anatomy and diagnostic imaging

  • Charles RaybaudEmail author
  • Vijay Ramaswamy
  • Michael D. Taylor
  • Suzanne Laughlin
Special Annual Issue

Abstract

Introduction

Modern understanding of the relation between the mutated cancer stem cell and its site of origin and of its interaction with the tissue environment is enhancing the importance of developmental anatomy in the diagnostic assessment of posterior fossa tumors in children. The aim of this review is to show how MR imaging can improve on the exact identification of the tumors in the brainstem and in the vicinity of the fourth ventricle in children, using both structural imaging data and a precise topographical assessment guided by the developmental anatomy.

Results

The development of the hindbrain results from complex processes of brainstem segmentation, ventro-dorsal patterning, multiple germinative zones, and diverse migration pathways of the neural progenitors. Depending on their origin in the brainstem, gliomas may be infiltrative or not, as well as overwhelmingly malignant (pons), or mostly benign (cervicomedullary, medullo-pontine tegmental, gliomas of the cerebellar peduncles). In the vicinity of the fourth ventricles, the prognosis of the medulloblastomas (MB) correlates the molecular subtyping as well as the site of origin: WNT MB develop from the Wnt-expressing lower rhombic lip and have a good prognosis; SHH MB develop from the Shh-modulated cerebellar cortex with an intermediate prognosis (dependent on age); recurrences are local mostly. The poor prognosis group 3 MB is radiologically heterogeneous: some tumors present classic features but are juxtaventricular (rather than intraventricular); others have highly malignant features with a small principal tumor and an early dissemination. Group 4 MB has classic features, but characteristically usually does not enhance; dissemination is common. Although there is as yet no clear molecular subgrouping of the ependymomas, their sites of origin and their development can be clearly categorized, as most develop in an exophytic way from the ventricular surface of the medulla in clearly specific locations: the obex region with expansion in the cistern magna, or the lateral recess region with expansion in the CPA and prepontine cisterns (cerebellar ependymomas, and still more intra-brainstem ependymomas are rare). Finally, almost all cerebellar gliomas are pilocytic astrocytomas.

Conclusions

A developmental and anatomic approach to the posterior fossa tumors in children (together with diffusion imaging data) provides a reliable pre-surgical identification of the tumor and of its aggressiveness.

Keywords

Posterior fossa tumors MR imaging Brainstem glioma DIPG Medulloblastoma Ependymoma 

Notes

Conflict of interest

We have no conflict of interest.

References

  1. 1.
    Boydston WR, Sanford RA, Muhlbauer MS, et al. (1991-1992) Glioma of the tectum and periaqueductal region of the mesencephalon. Pediatr Neurosurg 17:234–238Google Scholar
  2. 2.
    Broniscer A, Laningham FH, Kocak M, et al. (2006) Intratumoral hemorrhage among children with newly diagnosed, diffuse brainstem glioma. Cancer 106:1364–1371CrossRefPubMedGoogle Scholar
  3. 3.
    Cambronero F, Puelles L (2000) Posterocaudal nuclear relationships in the avian medulla oblongata: a fate map with quail chick chimeras. J Comp Neurol 427:522–545CrossRefPubMedGoogle Scholar
  4. 4.
    Conway AE, Reddick WE, Yuan Y, et al. (2014) “Occult” post-contrast signal enhancement in pediatric diffuse intrinsic pontine glioma is the MRI marker of angiogenesis? Neuroradiology 56(5):405–412PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Curless RC, Bowen BC, Pattany PM, et al. (2002) Magnetic resonance spectroscopy in childhood brainstem tumors. Pediatr Neurol 26:374–378CrossRefPubMedGoogle Scholar
  6. 6.
    Dağlioğlu E, Çataltepe O, Akalan N (2003) Tectal gliomas in children: the implications for natural history and management strategy. Pediatr Neurosurg 38:223–231CrossRefPubMedGoogle Scholar
  7. 7.
    Epstein F, Wisoff J (1987) Intraaxial tumors of the cervicomedullary junction. J Neurosurg 67:483–487CrossRefPubMedGoogle Scholar
  8. 8.
    Epstein FJ, Farmer JP (1993) Brain-stem glioma growth patterns. J Neurosurg 78:408–412CrossRefPubMedGoogle Scholar
  9. 9.
    Gibson P, Tong Y, Robinson G, et al. (2010) Subtypes of medulloblastoma have distinct developmental origins. Nature 468:1095–1099PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Gilbertson RJ, Gutmann DH (2007) Tumorigenesis in the brain: location, location, location. Cancer Res 67(12):5579–5582CrossRefPubMedGoogle Scholar
  11. 11.
    Godfraind C, Kaczmarska J, Kocak M, et al. (2012) Distinct disease-risk groups in pediatric supratentorial and posterior fossa ependymomas. Acta Neuropathol 124(2):247–257PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Ikezaki K, Matsushima T, Inoue T, et al. (1993) Correlation of microanatomical localization with postoperative survival in posterior fossa ependymomas. Neurosurgery 32(1):38–44CrossRefPubMedGoogle Scholar
  13. 13.
    Jandial R, U H, Levy ML, Snyder EY (2008) Brain tumor stem cells and the tumor microenvironment. Neurosurg Focus 24(3-4):E27CrossRefPubMedGoogle Scholar
  14. 14.
    Konno H, Yamamoto T, Iwasaki Y, et al. (1985) A case of quadrigeminal hamartoma. Acta Neuropathol 68:155–159CrossRefPubMedGoogle Scholar
  15. 15.
    Kool M, Korshunov A, Remke M, et al. (2012) Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data on WNT, SHH, Group 3, and Group 4 medulloblastomas. Acta Neuropathol 123:473–484PubMedCentralCrossRefPubMedGoogle Scholar
  16. 16.
    Koral K, Mathis D, Gimi B, et al. (2013) Common pediatric cerebellar tumors: correlation between cell density and apparent diffusion coefficient metrics. Radiology 268(2):532–537CrossRefPubMedGoogle Scholar
  17. 17.
    Krieger MD, Blüml S, McComb JG (2003) Magnetic resonance spectroscopy of atypical diffuse pontine masses. Neurosurg Focus 15(1):E5CrossRefPubMedGoogle Scholar
  18. 18.
    Laprie A, Pirzkall A, Haas-Kogan DA, et al. (2005) Longitudinal multivoxel MR spectroscopy study of pediatric diffuse brainstem glioma treated with radiotherapy. Int J Radiat Oncol Biol Phys 62:20–31CrossRefPubMedGoogle Scholar
  19. 19.
    Löbel U, Sedlacik J, Sabin ND, et al. (2010) Three-dimensional susceptibility-weighted imaging and two-dimensional T2*-weighted gradient-echo imaging of intratumoral hemorrhages in pediatric diffuse intrinsic pontine glioma. Neuroradiology 52:1167–1177PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Löbel U, Sedlacik J, Reddick WE, et al. (2010) Quantitative diffusion-weighted and dynamic susceptibility-weighted contrast-enhanced perfusion MR imaging analysis of T2 hypointense lesion components in pediatric diffuse intrinsic pontine glioma. AJNR Am J Neuroradiol 32(2):315–322PubMedCentralCrossRefPubMedGoogle Scholar
  21. 21.
    Louis DN, Ohgaki H, Wiestler OD, et al. (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114(2):97–109PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Mack SC, Witt H, Piro RM, et al. (2014) Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Nature 506:445–450PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Marcorelles P, Fallet-Bianco C, Oury JF, et al. (2005) Fetal aqueductal glioneuronal hamartoma: a clinicopathological and physiopathological study of three cases. Clin Neuropathol 24:155–162PubMedGoogle Scholar
  24. 24.
    Martinez S, Audreu A, Mecklenburg N, Echevarria D (2013) Cellular and molecular basis of cerebellar development. Front Neuroanat 7:18PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Nakamura H, Watanabe Y (2005) Isthmus organizer and regionalization of the mesencephalon and metencephalon. Int J Dev Biol 49:231–235CrossRefPubMedGoogle Scholar
  26. 26.
    Northcott PA, Korshunov A, Witt H, et al. (2011) Medulloblastoma comprises four distinct molecular variants. J Clin Oncol 29(11):1408–1414CrossRefPubMedGoogle Scholar
  27. 27.
    Northcott PA, Korshunov A, Pfister SM, Taylor MD (2012) The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 8:340–351CrossRefPubMedGoogle Scholar
  28. 28.
    Panigrahy A, Nelson Jr MD, Finlay JL, et al. (2008) Metabolism of diffuse intrinsic brainstem gliomas in children. Neuro-Oncology 10(1):32–44PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Panigrahy A, Nelson Jr MD, Blüml S (2010) Magnetic resonance spectroscopy in pediatric neuroradiology: clinical and research applications. Pediatr Radiol 40(1):3–30CrossRefPubMedGoogle Scholar
  30. 30.
    Pajtler K, Witt H, Sill M et al. The ependymoma classification. Cancer Cell 2015 (accepted).Google Scholar
  31. 31.
    Perreault S, Ramaswamy V, Achrol AS, et al. (2014) MRI surrogates for molecular subgroups of medulloblastoma. AJNR Am J Neuroradiol 35:1263–1269CrossRefPubMedGoogle Scholar
  32. 32.
    Raghunathan A, Wani K, Armstrong TS, et al. (2013) Histological predictors of outcome in ependymoma are dependent on anatomic site within the central nervous system. Brain Pathol 23:584–594CrossRefPubMedGoogle Scholar
  33. 33.
    Ramaswamy V, Remke M, Bouffet E, et al. (2013) Recurrence patterns across medulloblastoma subgroups: an integrated clinical and molecular analysis. Lancet Oncol 14(12):1200–1207PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Ramaswamy V, Remke M, Shih D, et al. (2014) Duration of the pre-diagnostic interval in medulloblastoma is subgroup dependent. Pediatr Blood Cancer 61(7):1190–1194CrossRefPubMedGoogle Scholar
  35. 35.
    Ramaswamy V, Remke M, Adamski J et al. Medulloblastoma subgroup-specific outcomes in irradiated children: who are the true high-risk patients? Neuro-Oncology 2015. [Epub ahead of print]
  36. 36.
    Rauscher A, Sedlacik J, Barth M, et al. (2005) Noninvasive assessment of vascular architecture and function during modulated blood oxygenation using susceptibility-weighted magnetic resonance imaging. Magn Reson Med 54:87–95CrossRefPubMedGoogle Scholar
  37. 37.
    Robertson PL, Murazko KM, Brunberg JA, et al. (1995) Pediatric midbrain tumors: a benign subgroup of brainstem gliomas. Pediatr Neurosurg 22:65–73CrossRefPubMedGoogle Scholar
  38. 38.
    Rodriguez Gutierrez D, Awwad A, Meijer L, et al. (2014) Metrics and textural features of MRI diffusion to improve classification of pediatric posterior fossa tumors. AJNR Am J Neuroradiol 35:1009–1015CrossRefPubMedGoogle Scholar
  39. 39.
    Roussel MF, Hatten ME (2011) Cerebellum: development and medulloblastoma. Curr Top Dev Biol 94:235–282PubMedCentralCrossRefPubMedGoogle Scholar
  40. 40.
    Sanford RA, Bebin J, Smith WR (1982) Pencil glioma of the aqueduct of Sylvius. J Neurosurg 57:690–696CrossRefPubMedGoogle Scholar
  41. 41.
    Sehgal V, Delproposto Z, Haacke EM, et al. (2005) Clinical applications of neuroimaging with susceptibility-weighted imaging. J Magn Reson Imaging 22:439–450CrossRefPubMedGoogle Scholar
  42. 42.
    Sehgal V, Delproposto Z, Haddar D, et al. (2006) Susceptibility-weighted imaging to visualize blood products and improve tumor contrast in the study of brain masses. J Magn Reson Imaging 24:41–51CrossRefPubMedGoogle Scholar
  43. 43.
    Sgaier SK, Millet S, Villanueva MP, et al. (2005) Morphogenetic and cellular movements that shape the mouse cerebellum; insights from genetic fate mapping. Neuron 45(1):27–40PubMedGoogle Scholar
  44. 44.
    Sun B, Wang CC, Wang G (1999) MRI characteristics of midbrain tumors. Neuroradiology 41:158–162CrossRefPubMedGoogle Scholar
  45. 45.
    Taylor MD, Poppleton H, Fuller C, et al. (2005) Radial glia cells are candidate stem cells of ependymoma. Cancer Cell 8:323–335CrossRefPubMedGoogle Scholar
  46. 46.
    Taylor MD, Northcott PA, Korshunov A, et al. (2012) Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 123:465–472PubMedCentralCrossRefPubMedGoogle Scholar
  47. 47.
    ten Donkelaar HJ, Lammens M, Cruysberg JRM, Cremers CWJR (2006) Development and developmental disorders of the cranial nerves. In: ten Donkelaar HJ, Lammens M, Hori A (eds) Clinical Neuroembryology. Springer-Verlag, Berlin Heidelberg, pp. 274–279CrossRefGoogle Scholar
  48. 48.
    Ternier J, Wray A, Puget S, et al. (2006) Tectal plate lesions in children. J Neurosurg 104(6 Suppl Pediatrics):369–373PubMedGoogle Scholar
  49. 49.
    Tihan T, Zhou T, Holmes E, et al. (2008) The prognostic value of histological grading of posterior fossa ependymomas in children: a children’s oncology group study and a review of prognostic factors. Mod Pathol 21:165–177PubMedGoogle Scholar
  50. 50.
    Tümpel S, Wiedemann KR (2009) Hox genes and segmentation of the vertebrate hindbrain. Curr Top Dev Biol 88:103–137CrossRefPubMedGoogle Scholar
  51. 51.
    U-King-Im JM, Taylor MD, Raybaud C (2010) Posterior fossa ependymomas: new radiological classification with surgical correlation. Childs Nerv Syst 26:1765–1772CrossRefPubMedGoogle Scholar
  52. 52.
    Vandertop WP, Hoffman HJ, Drake JM, et al. (1992) Focal midbrain tumors in children. Neurosurgery 31:186–194CrossRefPubMedGoogle Scholar
  53. 53.
    Witt H, Mack SC, Ryzhova M, et al. (2011) Delineation of two clinically and molecularly distinct subgroups of posterior fossa ependymoma. Cancer Cell 20:143–157PubMedCentralCrossRefPubMedGoogle Scholar
  54. 54.
    Witt H, Korshunov A, Pfister SM, Milde T (2012) Molecular approaches to ependymoma: the next step(s). Curr Opin Neurol 25(6):745–750CrossRefPubMedGoogle Scholar
  55. 55.
    Wullimann MF, Mueller T, Distel M, et al. (2011) The long adventurous journey of rhombic lip cells in jawed vertebrate: a comparative development analysis. Front Neuroanat 5:27PubMedCentralCrossRefPubMedGoogle Scholar
  56. 56.
    Xu Q, Wilkinson DG (2013) Boundary formation in the development of the vertebrate hindbrain. WIREs Dev Biol 2:735–745CrossRefGoogle Scholar
  57. 57.
    Yeom KW, Mobley BC, Lober MR, et al. (2013) Distinctive MRI features of pediatric medulloblastoma subtypes. AJNR Am J Neuroradiol 200:895–903Google Scholar
  58. 58.
    Zhukova N, Ramaswamy V, Remke M, et al. (2013) Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. Clin Oncol 31(23):2927–2935CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Charles Raybaud
    • 1
    Email author
  • Vijay Ramaswamy
    • 2
  • Michael D. Taylor
    • 3
  • Suzanne Laughlin
    • 1
  1. 1.Pediatric NeuroradiologyHospital for Sick ChildrenTorontoCanada
  2. 2.NeurooncologyHospital for Sick ChildrenTorontoCanada
  3. 3.NeurosurgeryHospital for Sick ChildrenTorontoCanada

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