title: Extraneural metastases in glioblastoma patients: two cases with YKL-40-positive glioblastomas and a meta-analysis of the literature.
abstract: 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.
authors.forename: Elena
authors.initials: E
authors.lastname: Anghileri
authors.affiliation: Unit of Neurology VIII-Molecular Neuro-Oncology, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy. anghileri.e@istituto-besta.it.
authors.forename: Anghileri
authors.initials: A
authors.lastname: Elena
authors.forename: Melina
authors.initials: M
authors.lastname: Castiglione
authors.affiliation: Neurosurgery Unit, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Castiglione
authors.initials: C
authors.lastname: Melina
authors.forename: Raffaele
authors.initials: R
authors.lastname: Nunziata
authors.affiliation: Pathological Unit, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Nunziata
authors.initials: N
authors.lastname: Raffaele
authors.forename: Carlo
authors.initials: C
authors.lastname: Boffano
authors.affiliation: Neuro-radiological Unit, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Boffano
authors.initials: B
authors.lastname: Carlo
authors.forename: Vittoria
authors.initials: V
authors.lastname: Nazzi
authors.affiliation: Neurosurgery Unit, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Nazzi
authors.initials: N
authors.lastname: Vittoria
authors.forename: Francesco
authors.initials: F
authors.lastname: Acerbi
authors.affiliation: Neurosurgery Unit, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Acerbi
authors.initials: A
authors.lastname: Francesco
authors.forename: Gaetano
authors.initials: G
authors.lastname: Finocchiaro
authors.affiliation: Unit of Neurology VIII-Molecular Neuro-Oncology, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Finocchiaro
authors.initials: F
authors.lastname: Gaetano
authors.forename: Marica
authors.initials: M
authors.lastname: Eoli
authors.affiliation: Unit of Neurology VIII-Molecular Neuro-Oncology, Foundation I.R.C.C.S., Neurological National Institute C. Besta, Milan, Italy.
authors.forename: Eoli
authors.initials: E
authors.lastname: Marica
mesh_terms: D054392:Adipokines / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000556:secondary* / Q000601:surgery; D000071451:Chitinase-3-Like Protein 1; D003131:Combined Modality Therapy; D017809:Fatal Outcome; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D006801:Humans; D037102:Lectins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D019635:Neurosurgical Procedures; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D037102:Lectins
keywords: Bevacizumab; Glioblastoma (GBM); Long-term survival; Metastases; YKL-40