Skip to main content
SpringerLink
Log in

Increasing value of autopsies in patients with brain tumors in the molecular era

  • Clinical Study
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background

Pediatric brain tumors are associated with high morbidity and mortality, in part due to insufficient understanding of tumor biology. With limited tissue allocation for research from surgical specimens, a key barrier to improving biological understanding, brain tumor autopsies have become an increasingly valuable resource. This study reviews the brain tumor autopsy practice at our institution and describes specific emerging research utilization patterns beyond the clinical autopsy report.

Methods

We performed a retrospective analysis of brain tumor autopsies at Boston Children’s Hospital (BCH) between 2007 and 2017 and reviewed their consents, neuropathology reports and final diagnoses. We reviewed the method of tissue triaging for research consented autopsies (bioregistry, frozen and fresh tissue) and documented their specific uses.

Results

Ninety-six deaths at BCH were due to brain tumors; 56 autopsies were performed (58.3%), of which 49 (87.5%) were consented for research. Tumor mapping was performed on all cases and tissue was allocated for DNA- and RNA-based sequencing studies (published and ongoing). Three tissue allocations with a postmortem interval of 8 h or less resulted in successful cell lines. Tissue from 14 autopsies was contributed to the National DIPG Registry.

Conclusion

Our institutional pediatric brain tumor autopsy clinical experience demonstrates the increased utility and wide utilization of autopsy-derived tissue for multiple types of research. These results support the increased efforts to obtain research consent for brain tumor autopsy and active collection of unfixed autopsy material in the molecular era.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Curtin SC, Minino AM, Anderson RN (2016) Declines in cancer death rates among children and adolescents in the United States, 1999-2014. NCHS Data Brief 257:1–8

    Google Scholar 

  2. Ostrom QT, Gittleman H, Truitt G, Boscia A, Kruchko C, Barnholtz-Sloan JS (2018) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2011–2015. Neuro-oncology 20:iv1–iv86

    Article  Google Scholar 

  3. Guerreiro Stucklin AS, Ramaswamy V, Daniels C, Taylor MD (2018) Review of molecular classification and treatment implications of pediatric brain tumors. Curr Opin Pediatr 30:3–9

    Article  CAS  Google Scholar 

  4. Nemetz PN, Tanglos E, Sands LP, Fisher WP, Newman WP, Burton EC (2006) Attitudes toward the autopsy—an 8-state survey. MedGenMed 8(3):80

    PubMed  PubMed Central  Google Scholar 

  5. Kumar P, Angst DB, Taxy J, Mangurten HH (2000) Neonatal autopsies: a 10-year experience. Arch Pediatr Adolesc Med 154(1):38–42

    CAS  PubMed  Google Scholar 

  6. Newton D, Coffin CM, Clark EB, Lowichik A (2004) How the pediatric autopsy yields valuable information in a vertically integrated health care system. Arch Pathol Lab Med 128(11):1239–1246

    PubMed  Google Scholar 

  7. Shojania KG, Burton EC (2008) The vanishing nonforensic autopsy. N Engl J Med 358(9):873–875

    Article  CAS  Google Scholar 

  8. Loughrey MB, McCluggage WG, Toner PG (2000) The declining autopsy rate and clinicians' attitudes. Ulster Med J 69(2):83–89

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Lundberg GD (1996) College of American Pathologists Conference XXIX on restructuring autopsy practice for health care reform. Let's make this autopsy conference matter. Arch Pathol Lab Med 120(8):736–738

    CAS  PubMed  Google Scholar 

  10. Sullivan J, Monagle P (2011) Bereaved parents' perceptions of the autopsy examination of their child. Pediatrics 127(4):e1013–e1020

    Article  Google Scholar 

  11. Odendaal HJ, Elliott A, Kinney HC, Human M, Gaspar D, Petersen D et al (2011) Consent for autopsy research for unexpected death in early life. Obstet Gynecol 17(1):167–171

    Article  Google Scholar 

  12. Wiener L, Sweeney C, Baird K, Merchant MS, Warren KE, Corner GW et al (2014) What do parents want to know when considering autopsy for their child with cancer? J Pediatr Hematol Oncol 36(6):464–470

    Article  Google Scholar 

  13. Pentz RD, Cohen CB, Wicclair M, DeVita MA, Flamm AL, Youngner SJ et al (2005) Ethics guidelines for research with the recently dead. Nat Med 11(11):1145–1149

    Article  CAS  Google Scholar 

  14. Kieran MW (2015) Time to rethink the unthinkable: upfront biopsy of children with newly diagnosed diffuse intrinsic pontine glioma (DIPG). Pediatr Blood Cancer 62(1):3–4

    Article  Google Scholar 

  15. Puget S, Beccaria K, Blauwblomme T, Roujeau T, James S, Grill J et al (2015) Biopsy in a series of 130 pediatric diffuse intrinsic Pontine gliomas. Childs Nerv Syst 31(10):1773–1780

    Article  Google Scholar 

  16. Baugh J, Bartels U, Leach J, Jones B, Chaney B, Warren KE et al (2017) The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease. J Neurooncol 132(2):323–331

    Article  Google Scholar 

  17. Broniscer A, Baker JN, Baker SJ, Chi SN, Geyer JR, Morris EB et al (2010) Prospective collection of tissue samples at autopsy in children with diffuse intrinsic pontine glioma. Cancer 116(19):4632–4637

    Article  Google Scholar 

  18. Lin GL, Monje M (2017) A protocol for rapid post-mortem cell culture of diffuse intrinsic pontine glioma (DIPG). J Vis Exp 121:55360

    Google Scholar 

  19. Grasso CS, Tang Y, Truffaux N, Berlow NE, Liu L, Debily MA et al (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21(6):555–559

    Article  CAS  Google Scholar 

  20. Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Excalante LE, Mathewson ND et al (2018) Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq. Science 360(6386):331–335

    Article  CAS  Google Scholar 

  21. Hulette CM, Welsh-Bohmer KA, Crain B, Szymanski MH, Sinclaire NO, Noses AD (1997) Rapid brain autopsy. The Joseph and Kathleen Bryan Alzheimer's Disease Research Center experience. Arch Pathol Lab Med 121(6):615–618

    CAS  PubMed  Google Scholar 

  22. Kambhampati M, Perez JP, Yadavilli S, Saratsis AM, Hill AD, Ho CY et al (2015) A standardized autopsy procurement allows for the comprehensive study of DIPG biology. Oncotarget 6(14):12740–12747

    Article  Google Scholar 

  23. Ghorpade A, Bruch L, Persidsky Y, Chin B, Brown WH, Borgmann K et al (2005) Development of a rapid autopsy program for studies of brain immunity. J Neuroimmunol 163(1–2):135–144

    Article  CAS  Google Scholar 

  24. Robin MA, Putzi M, Mucci N, Smith DC, Wojno K, Korenchuk S et al (2000) Rapid (“warm”) autopsy study for procurement of metastatic prostate cancer. Clin Cancer Res 6(3):1038–1045

    Google Scholar 

  25. Lindell KO, Erlen JA, Kaminski N (2006) Lessons from our patients: development of a warm autopsy program. PLoS Med 3(7):e234

    Article  Google Scholar 

  26. Bavi P, Siva M, Abi-Saab T, Chadwick D, Dhani N, Butany J et al (2019) DEveloping a pan-cancer research autopsy programme. J Clin Pathol. https://doi.org/10.1136/jclinpath-2019-205874

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pisapia DJ, Salvatore S, Pauli C, Hissong E, Eng K, Prandi D et al (2017) Next-generation rapid autopsies enable tumor evolution tracking and generation of preclinical models. JCO Precis Oncol 1:1–13

    Google Scholar 

  28. Hoffman LM, DeWire M, Ryall S, Buczkowicz P, Leach J, Miles L et al (2016) Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. Acta Neuropathol Commun 4:1

    Article  Google Scholar 

Download references

Acknowledgements

We are grateful for the support we receive from the pathology assistants and autopsy technicians, as well as for the support and collaboration of Boston Children’s Hospital Biorepository. Also, we acknowledge and thank the families that consented to autopsy research.

Funding

No funds were used for this particular manuscript and analysis.

Author information

Author notes

  1. Mark W. Kieran

    Present address: Brystol Meyers Squibb, New York, USA

Authors and Affiliations

  1. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, USA

    Jared T. Ahrendsen

  2. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, USA

    Mariella G. Filbin, Susan N. Chi, Peter E. Manley, Karen D. Wright, Pratiti Bandopadhayay, Jessica R. Clymer, Kee Kiat Yeo, Mark W. Kieran, Robert Jones & Sanda Alexandrescu

  3. Department of Pathology, Brigham and Women’s Hospital, Boston, USA

    Keith L. Ligon

  4. Department of Pathology, Boston Children’s Hospital, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02215, USA

    Hart G. Lidov, Keith L. Ligon & Sanda Alexandrescu

Authors
  1. Jared T. Ahrendsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mariella G. Filbin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Susan N. Chi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peter E. Manley
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Karen D. Wright
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Pratiti Bandopadhayay
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jessica R. Clymer
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kee Kiat Yeo
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Mark W. Kieran
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Robert Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hart G. Lidov
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Keith L. Ligon
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Sanda Alexandrescu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sanda Alexandrescu.

Ethics declarations

Conflict of interest

The authors of this manuscript have no conflict of interest to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Electronic supplementary material 1 (PDF 226 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahrendsen, J.T., Filbin, M.G., Chi, S.N. et al. Increasing value of autopsies in patients with brain tumors in the molecular era. J Neurooncol 145, 349–355 (2019). https://doi.org/10.1007/s11060-019-03302-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-019-03302-z

Keywords

Search

Navigation