Child's Nervous System

, Volume 31, Issue 10, pp 1773–1780 | Cite as

Biopsy in a series of 130 pediatric diffuse intrinsic Pontine gliomas

  • Stephanie Puget
  • Kevin Beccaria
  • Thomas Blauwblomme
  • Thomas Roujeau
  • Syril James
  • Jacques Grill
  • Michel Zerah
  • Pascale Varlet
  • Christian Sainte-Rose
Special Annual Issue

Abstract

Purpose

Diffuse intrinsic pontine glioma (DIPG) is the most severe pediatric solid tumor, with no significant improvement in the past 50 years. Possible reasons for failure to make therapeutic progress include poor understanding of the underlying molecular biology due to lack of tumor material.

Methods

We performed a prospective analysis of children with typical appearance of DIPG who had a stereotactic biopsy in our unit since 2002. Technical approach, complications, histopathological results, and samples processing are exposed. The literature on this subject is discussed.

Results

Reviewing our own 130 cases of DIPG biopsies and previous published data, these procedures appear to have a diagnostic yield and morbidity rates similar to those reported for other brain locations (3.9 % of transient morbidity in our series). In addition, the quality and the quantity of the material obtained allow to (1) confirm the diagnosis, (2) reveal that WHO grading was useless to predict outcome, and (3) perform an extended molecular screen, including biomarkers study and the development of preclinical models. Recent studies reveal that DIPG may comprise more than one biological entity and a unique oncogenesis involving mutations never described in other types of cancers, i.e., histones H3 K27M and activin receptor ACVR1.

Conclusion

Stereotactic biopsies of DIPG can be considered as a safe procedure in well-trained neurosurgical teams and could be incorporated in protocols. It is a unique opportunity to integrate DIPG biopsies in clinical practice and use the biology at diagnosis to drive the introduction of innovative targeted therapies, in combination with radiotherapy.

Keywords

Biopsy Pediatric DIPG Targeted therapy Brain stem tumor 

References

  1. 1.
    Jansen MH, van Vuurden DG, Vandertop WP, Kaspers GJ (2012) Diffuse intrinsic pontine gliomas: a systematic update on clinical trials and biology. Cancer Treat Rev 38:27–35. doi:10.1016/j.ctrv.2011.06.007 CrossRefPubMedGoogle Scholar
  2. 2.
    Warren KE, Killian K, Suuriniemi M, et al. (2012) Genomic aberrations in pediatric diffuse intrinsic pontine gliomas. Neuro-Oncology 14:326–332. doi:10.1093/neuonc/nor190 PubMedCentralCrossRefPubMedGoogle Scholar
  3. 3.
    Epstein F, Wisoff JH (1988) Intrinsic brainstem tumors in childhood: surgical indications. J Neuro-Oncol 6:309–317CrossRefGoogle Scholar
  4. 4.
    Bax DA, Mackay A, Little SE, et al. (2010) A distinct spectrum of copy number aberrations in pediatric high-grade gliomas. Clin Cancer Res 16:3368–3377. doi:10.1158/1078-0432.CCR-10-0438 PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Paugh BS, Broniscer A, Qu C, et al. (2011) Genome-wide analyses identify recurrent amplifications of receptor tyrosine kinases and cell-cycle regulatory genes in diffuse intrinsic pontine glioma. J Clin Oncol 29:3999–4006. doi:10.1200/JCO.2011.35.5677 PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Qu HQ, Jacob K, Fatet S, et al. (2010) Genome-wide profiling using single-nucleotide polymorphism arrays identifies novel chromosomal imbalances in pediatric glioblastomas. Neuro-Oncology 12:153–163. doi:10.1093/neuonc/nop001 PubMedCentralCrossRefPubMedGoogle Scholar
  7. 7.
    Zarghooni M, Bartels U, Lee E, et al. (2010) Whole-genome profiling of pediatric diffuse intrinsic pontine gliomas highlights platelet-derived growth factor receptor alpha and poly (ADP-ribose) polymerase as potential therapeutic targets. J Clin Oncol 28:1337–1344. doi:10.1200/JCO.2009.25.5463 CrossRefPubMedGoogle Scholar
  8. 8.
    Roujeau T, Machado G, Garnett MR, et al. (2007) Stereotactic biopsy of diffuse pontine lesions in children. J Neurosurg 107:1–4. doi:10.3171/PED-07/07/001 CrossRefPubMedGoogle Scholar
  9. 9.
    Robison NJ, Kieran MW (2014) Diffuse intrinsic pontine glioma: a reassessment. J Neurooncol 119:7–15. doi:10.1007/s11060-014-1448-8 CrossRefPubMedGoogle Scholar
  10. 10.
    Puget S, Philippe C, Bax DA, et al. (2012) Mesenchymal transition and PDGFRA amplification/mutation are key distinct oncogenic events in pediatric diffuse intrinsic pontine gliomas. PLoS One 7:e30313. doi: 10.1371/journal.pone.0030313
  11. 11.
    Kieran MW (2015) Time to rethink the unthinkable: upfront biopsy of children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Pediatr Blood Cancer 62:3–4. doi:10.1002/pbc.25266 CrossRefPubMedGoogle Scholar
  12. 12.
    Gleason CA, Wise BL, Feinstein B (1978) Stereotactic localization (with computerized tomographic scanning), biopsy, and radiofrequency treatment of deep brain lesions. Neurosurgery 2:217–222CrossRefPubMedGoogle Scholar
  13. 13.
    Epstein F, McCleary EL (1986) Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg 64:11–15. doi:10.3171/jns.1986.64.1.0011 CrossRefPubMedGoogle Scholar
  14. 14.
    Stroink AR, Hoffman HJ, Hendrick EB, Humphreys RP (1986) Diagnosis and management of pediatric brain-stem gliomas. J Neurosurg 65:745–750. doi:10.3171/jns.1986.65.6.0745 CrossRefPubMedGoogle Scholar
  15. 15.
    Albright AL, Packer RJ, Zimmerman R, et al. (1993) Magnetic resonance scans should replace biopsies for the diagnosis of diffuse brain stem gliomas: a report from the Children’s Cancer Group. Neurosurgery 33:1026–1029 discussion 1029–30CrossRefPubMedGoogle Scholar
  16. 16.
    Chico-Ponce de Leon F, Perezpena-Diazconti M, Castro-Sierra E, et al. (2003) Stereotactically-guided biopsies of brainstem tumors. Childs Nerv Syst 19:305–310. doi:10.1007/s00381-003-0737-x CrossRefPubMedGoogle Scholar
  17. 17.
    Dellaretti M, Touzet G, Reyns N, et al. (2011) Correlation among magnetic resonance imaging findings, prognostic factors for survival, and histological diagnosis of intrinsic brainstem lesions in children. J Neurosurg Pediatr 8:539–543. doi:10.3171/2011.9.PEDS1167 CrossRefPubMedGoogle Scholar
  18. 18.
    Leach PA, Estlin EJ, Coope DJ, et al. (2008) Diffuse brainstem gliomas in children: should we or shouldn’t we biopsy? Br J Neurosurg 22:619–624. doi:10.1080/02688690802366198 CrossRefPubMedGoogle Scholar
  19. 19.
    Pincus DW, Richter EO, Yachnis AT, et al. (2006) Brainstem stereotactic biopsy sampling in children. J Neurosurg 104:108–114. doi:10.3171/ped.2006.104.2.108 PubMedGoogle Scholar
  20. 20.
    Rajshekhar V, Moorthy RK (2010) Status of stereotactic biopsy in children with brain stem masses: insights from a series of 106 patients. Stereotact Funct Neurosurg 88:360–366. doi:10.1159/000319044 CrossRefPubMedGoogle Scholar
  21. 21.
    St George EJ, Walsh AR, Sgouros S (2004) Stereotactic biopsy of brain tumours in the paediatric population. Childs Nerv Syst 20:163–167. doi:10.1007/s00381-003-0897-8 CrossRefPubMedGoogle Scholar
  22. 22.
    Valdes-Gorcia J, Espinoza-Diaz DM, Paredes-Diaz E (1998) Stereotactic biopsy of brain stem and posterior fossa lesions in children. Acta Neurochir 140:899–903CrossRefPubMedGoogle Scholar
  23. 23.
    Puget S, Blauwblomme T, Grill J (2012) Is biopsy safe in children with newly diagnosed diffuse intrinsic pontine glioma? Am Soc Clin Oncol Educ Book 629–633. doi: 10.14694/EdBook_AM.2012.32.629
  24. 24.
    Hankinson TC, Campagna EJ, Foreman NK, Handler MH (2011) Interpretation of magnetic resonance images in diffuse intrinsic pontine glioma: a survey of pediatric neurosurgeons. J Neurosurg Pediatr 8:97–102. doi:10.3171/2011.4.PEDS1180 CrossRefPubMedGoogle Scholar
  25. 25.
    Sufit A, Donson AM, Birks DK, et al. (2012) Diffuse intrinsic pontine tumors: a study of primitive neuroectodermal tumors versus the more common diffuse intrinsic pontine gliomas. J Neurosurg Pediatr 10:81–88. doi:10.3171/2012.3.PEDS11316 CrossRefPubMedGoogle Scholar
  26. 26.
    Samadani U, Judy KD (2003) Stereotactic brainstem biopsy is indicated for the diagnosis of a vast array of brainstem pathology. Stereotact Funct Neurosurg 81:5–9. doi:10.1159/000075097 CrossRefPubMedGoogle Scholar
  27. 27.
    Wang ZJ, Rao L, Bhambhani K, et al. (2015) Diffuse intrinsic pontine glioma biopsy: a single institution experience. Pediatr Blood Cancer 62:163–165. doi:10.1002/pbc.25224 CrossRefPubMedGoogle Scholar
  28. 28.
    McGirt MJ, Woodworth GF, Coon AL, et al. (2005) Independent predictors of morbidity after image-guided stereotactic brain biopsy: a risk assessment of 270 cases. J Neurosurg 102:897–901. doi:10.3171/jns.2005.102.5.0897 CrossRefPubMedGoogle Scholar
  29. 29.
    Geoerger B, Hargrave D, Thomas F, et al. (2011) Innovative therapies for children with cancer pediatric phase I study of erlotinib in brainstem glioma and relapsing/refractory brain tumors. Neuro-Oncology 13:109–118. doi:10.1093/neuonc/noq141 PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Buczkowicz P, Hoeman C, Rakopoulos P, et al. (2014) Genomic analysis of diffuse intrinsic pontine gliomas identifies three molecular subgroups and recurrent activating ACVR1 mutations. Nat Genet 46:451–456. doi:10.1038/ng.2936 PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Grill J, Puget S, Andreiuolo F, et al. (2012) Critical oncogenic mutations in newly diagnosed pediatric diffuse intrinsic pontine glioma. Pediatr Blood Cancer 58:489–491. doi:10.1002/pbc.24060 CrossRefPubMedGoogle Scholar
  32. 32.
    Backlund EO (1971) A new instrument for stereotaxic brain tumour biopsy. Technical note. Acta Chir Scand 137:825–827PubMedGoogle Scholar
  33. 33.
    Dellaretti M, Reyns N, Touzet G, et al. (2012) Stereotactic biopsy for brainstem tumors: comparison of transcerebellar with transfrontal approach. Stereotact Funct Neurosurg 90:79–83. doi:10.1159/000335502 CrossRefPubMedGoogle Scholar
  34. 34.
    Khatua S, Moore KR, Vats TS, Kestle JR (2011) Diffuse intrinsic pontine glioma—current status and future strategies. Childs Nerv Syst 27:1391–1397. doi:10.1007/s00381-011-1468-z CrossRefPubMedGoogle Scholar
  35. 35.
    Wilkinson R, Harris J (2008) Moral and legal reasons for altruism in the case of brainstem biopsy in diffuse glioma. Br J Neurosurg 22:617–618. doi:10.1080/02688690802482896 CrossRefPubMedGoogle Scholar
  36. 36.
    Thirant C, Bessette B, Varlet P, et al. (2011) Clinical relevance of tumor cells with stem-like properties in pediatric brain tumors. PLoS One 6:e16375. doi: 10.1371/journal.pone.0016375
  37. 37.
    Taylor KR, Mackay A, Truffaux N, et al. (2014) Recurrent activating ACVR1 mutations in diffuse intrinsic pontine glioma. Nat Genet 46:457–461. doi:10.1038/ng.2925 PubMedCentralCrossRefPubMedGoogle Scholar
  38. 38.
    Wu G, Broniscer A, McEachron TA, et al. (2012) Somatic histone H3 alterations in pediatric diffuse intrinsic pontine gliomas and non-brainstem glioblastomas. Nat Genet 44:251–253. doi:10.1038/ng.1102 PubMedCentralCrossRefPubMedGoogle Scholar
  39. 39.
    Bender S, Tang Y, Lindroth AM, et al. (2013) Reduced H3K27me3 and DNA hypomethylation are major drivers of gene expression in K27M mutant pediatric high-grade gliomas. Cancer Cell 24:660–672. doi:10.1016/j.ccr.2013.10.006 CrossRefPubMedGoogle Scholar
  40. 40.
    Fontebasso AM, Papillon-Cavanagh S, Schwartzentruber J, et al. (2014) Recurrent somatic mutations in ACVR1 in pediatric midline high-grade astrocytoma. Nat Genet 46:462–466. doi:10.1038/ng.2950 PubMedCentralCrossRefPubMedGoogle Scholar
  41. 41.
    Paugh BS, Zhu X, Qu C, et al. (2013) Novel oncogenic PDGFRA mutations in pediatric high-grade gliomas. Cancer Res 73:6219–6229. doi:10.1158/0008-5472.CAN-13-1491 PubMedCentralCrossRefPubMedGoogle Scholar
  42. 42.
    Wu G, Diaz AK, Paugh BS, et al. (2014) The genomic landscape of diffuse intrinsic pontine glioma and pediatric non-brainstem high-grade glioma. Nat Genet 46:444–450. doi:10.1038/ng.2938 PubMedCentralCrossRefPubMedGoogle Scholar
  43. 43.
    Khuong-Quang DA, Buczkowicz P, Rakopoulos P, et al. (2012) K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas. Acta Neuropathol 124:439–447. doi:10.1007/s00401-012-0998-0 PubMedCentralCrossRefPubMedGoogle Scholar
  44. 44.
    Monje M, Mitra SS, Freret ME, et al. Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma. Proc Natl Acad Sci U S A 108:4453–4458. doi: 10.1073/pnas.1101657108
  45. 45.
    Veringa SJ, Biesmans D, van Vuurden DG, et al. (2013) In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma. PLoS One 8:e61512. doi: 10.1371/journal.pone.0061512
  46. 46.
    Bartels U, Hawkins C, Vezina G, et al. (2011) Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank: advancing basic and translational research and cooperation in DIPG. J Neurooncol 105:119–125. doi:10.1007/s11060-011-0704-4 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Stephanie Puget
    • 1
    • 2
    • 5
  • Kevin Beccaria
    • 1
    • 2
  • Thomas Blauwblomme
    • 1
    • 2
  • Thomas Roujeau
    • 1
    • 2
  • Syril James
    • 1
    • 2
  • Jacques Grill
    • 3
  • Michel Zerah
    • 1
    • 2
  • Pascale Varlet
    • 4
  • Christian Sainte-Rose
    • 1
    • 2
  1. 1.Department of Pediatric NeurosurgeryNecker Enfants Malades HospitalParisFrance
  2. 2.Sorbonne Paris CitéUniversité Paris DescartesParisFrance
  3. 3.Department of Pediatric and Adolescent Oncology and CNRS UMR 8203 “Vectorology and Anticancer Therapeutics”, Gustave Roussy Cancer InstituteUniversite Paris SudVillejuifFrance
  4. 4.Department of NeuropathologySainte-Anne HospitalParisFrance
  5. 5.UMR CNRS 8203 “Vectorologie et Thérapeutiques Anticancéreuses”, Département de Cancérologie de l’Enfant et de l’AdolescentInstitut de Cancérologie Gustave RoussyVillejuif cedexFrance

Personalised recommendations