Extracranial metastasis of gliobastoma: Three illustrative cases and current review of the molecular pathology and management strategies

Abstract

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.

Extraneural Glioblastoma Multiforme Vertebral Metastasis

“…1 Historically, GBMs were not believed to metastasize outside of the CNS because of the presence of the blood–brain barrier and overall low median survival; however, several reports of extraneural GBM metastases have been reported. 2,3 With improvements in the standard of care treatment of primary glioblastoma, including surgery, chemotherapy, and radiation, the incidence of extraneural metastases has increased exponentially. Lun et al reviewed 88 cases of extracranial GBM metastases published between 1928 and 2009 and found that the time from diagnosis of GBM to detection of extracranial metastases was 8.5 months and from time of metastasis to mortality was 1.5 months.…”

A Rare Cause of Lung Metastasis - Glioblastoma Multiforme

“…[4] Metastases are usually seen after resection of the primary tumor. [5] In the presently described cases, a mass lesion suggestive of primary pulmonary carcinoma was detected, but the pathological diagnosis was pulmonary metastasis of GBM.…”

“…[7] Craniotomy procedures and intraventricular shunting during the operation are thought to enable tumor cells to reach other regions of the body via lymphatic and hematogenous pathways. [5] In Case 1, lung metastasis was detected preoperatively before resection of the cranial tumor. In Case 2, lung metastasis developed after an initial cure was achieved with adjuvant CT and RT after the operation.…”

Metastatic Glioblastoma: A Case Report and Review of the Literature

“…There is a virtual lack of collagen and fibronectin within the central nervous system and, in general, glioma cells do not express fibronectin [8,9]. This lack of fibronectin expression is thought to inhibit vascular endothelial invasion and subsequent extracranial seeding.…”