title: Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies.
abstract: Glioblastoma (GBM) is the most common and the most malignant primary brain tumor in adults, accounting for ~12-15% of all intracranial neoplasms. Despite advances in surgical, medical and radiation therapies, the mortality of GBM remains high, with a median survival ranging between 40 and 70 weeks. Similar to other primary brain tumors, the extracranial metastasis of GBM is extremely rare, occurring in <2% of patients. To demonstrate the clinical characteristics of this rare tumor, we herein present three cases of extracranial GBM metastasis: One to the lungs, which represents the longest reported survival of lung metastases from GBM to date; the second to the soft tissue of the posterior neck; and the third to the lumbar intradural space. Unlike tumors elsewhere, there are unique barriers in the brain that prevent the hematogenous and lymphatic spread of intracranial tumors, such as the dura mater and the thickened basement membrane of the blood vessels. In addition, central nervous system tumor cells lack extracellular matrix proteins required to invade surrounding connective tissue, a prerequisite for tumor dissemination. In this study, we aimed to investigate the different possible mechanisms underlying the extracranial metastasis of GBM and determine the biomolecular and genetic characteristics differentiating GBMs that metastasize from those that do not. We also reviewed the role of systemic chemotherapy and bevacizumab in the treatment of disseminated GBMs. Early identification and differentiation of these tumors may enable patients to benefit from surgical resection, radiation and combination chemotherapy prior to developing other comorbidities from metastatic disease, which may translate into prolonged survival with an acceptable quality of life.
authors.affiliation: Brain Tumor and Neuro-Oncology Center and Department of Neurological Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Abhishek
authors.initials: A
authors.lastname: Ray
authors.affiliation: Brain Tumor and Neuro-Oncology Center and Department of Neurological Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Manjila
authors.affiliation: Brain Tumor and Neuro-Oncology Center and Department of Neurological Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Alia M
authors.initials: AM
authors.lastname: Hdeib
authors.affiliation: Department of Oncology, University Hospitals Case Medical Center, Seidman Cancer Center and Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
authors.forename: Archana
authors.initials: A
authors.lastname: Radhakrishnan
authors.affiliation: Department of Oncology, University Hospitals Case Medical Center, Seidman Cancer Center and Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Nock
authors.affiliation: Department of Pathology, University Hospitals Case Medical Center, Seidman Cancer Center and Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Cohen
authors.affiliation: Brain Tumor and Neuro-Oncology Center and Department of Neurological Surgery, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA ; Department of Pathology, University Hospitals Case Medical Center, Seidman Cancer Center and Case Comprehensive Cancer Center, Cleveland, OH 44106, USA.
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Sloan
keywords: bevacizumab; glial fibrillary acidic protein; glioblastoma; metastasis; temozolomide