Neurosurgical Review

, Volume 39, Issue 1, pp 37–46 | Cite as

Extraneural metastases in glioblastoma patients: two cases with YKL-40-positive glioblastomas and a meta-analysis of the literature

  • Anghileri ElenaEmail author
  • Castiglione Melina
  • Nunziata Raffaele
  • Boffano Carlo
  • Nazzi Vittoria
  • Acerbi Francesco
  • Finocchiaro Gaetano
  • Eoli Marica


Glioblastoma (GBM) are high-grade gliomas that severely impact on overall survival (OS). GBM cell motility and the breakdown of the blood–brain barrier could favor GBM cell communication with the systemic circulation. In spite of this, extracranial GBM metastases are rare. Here, we describe two YKL-40-positive GBM patients with extra-CNS (central nervous system) metastases, and we present a meta-analysis of 94 cases. The analysis concluded that extra-CNS metastases occurred 8.5 months after first GBM diagnosis and OS was 12 months; surgical GBM excision was associated at a longer interval to extra-CNS metastasis than biopsy only, and even longer if followed by radiotherapy and chemotherapy. Both our case reports were adult males who developed extra-CNS, YKL-40-positive metastases at lymph nodes, lung and subcutaneous sites, after 86 and 24 months from initial diagnosis of GBM. At first GBM local recurrence, they were treated with bevacizumab (BV), an anti-vascular endothelial growth factor antibody. They died after 4 and 1 month from the occurrence of metastases. Both cases expressed YKL-40 and lacked EGFR amplification, suggesting a mesenchymal phenotype, and maintained such profile at extra-CNS recurrence; they did not show MGMT promoter methylation, IDH1/2 mutations, or c-Met upregulation. Our two cases and the meta-analysis support the idea that prolonged survival of GBM patients increases the probability of GBM cells shedding to lymphatic and hematic system. Interestingly, the present two cases showed the features of mesenchymal profile, usually related with worst prognosis that was maintained in extracranial metastases.


Metastases Glioblastoma (GBM) Long-term survival YKL-40 Bevacizumab 



We would like to thank Dr. Chiara Calatozzolo for the immunohistochemistry evaluation and Dr. Rosina Paterra for EGFR amplification.

Conflict of interests

The authors declare that they have no competing interests.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Anghileri Elena
    • 1
    Email author
  • Castiglione Melina
    • 2
  • Nunziata Raffaele
    • 3
  • Boffano Carlo
    • 4
  • Nazzi Vittoria
    • 2
  • Acerbi Francesco
    • 2
  • Finocchiaro Gaetano
    • 1
  • Eoli Marica
    • 1
  1. 1.Unit of Neurology VIII-Molecular Neuro-OncologyFoundation I.R.C.C.S., Neurological National Institute C. BestaMilanItaly
  2. 2.Neurosurgery UnitFoundation I.R.C.C.S., Neurological National Institute C. BestaMilanItaly
  3. 3.Pathological UnitFoundation I.R.C.C.S., Neurological National Institute C. BestaMilanItaly
  4. 4.Neuro-radiological UnitFoundation I.R.C.C.S., Neurological National Institute C. BestaMilanItaly

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