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.

Keywords: bevacizumab; glial fibrillary acidic protein; glioblastoma; metastasis; temozolomide.

Figure 1.

Case 1: Contrast-enhanced magnetic resonance imaging (A) axial, (B) sagittal and (C) coronal sequences shows primary intracranial glioblastoma. Chest (D) X-ray and (E) contrast-enhanced computed tomography reveal metastatic glioblastoma to the lungs.

Figure 2.

Case 1: Needle biopsy of the lung demonstrated effacement of alveolar spaces by tumor on (A) hematoxylin and eosin (H&E) staining (magnification, x100) and (B) nests of metastatic glioma separated by alveolar septae on immunohistochemical staining for glial fibrillary acidic protein (GFAP) (magnification, x400). Case 2: Needle biopsy of the neck mass demonstrates tumor cells resembling the patient's original malignant glioma on (C) H&E staining (magnification, x200) and (D) glial differentiation within the tumor on GFAP immunohistochemical staining (magnification, x200). Case 3: Permanent surgical section of the intradural lumbosacral mass confirmed histopathological characteristics of glioblastoma on (E) H&E staining (magnification, x400) and (F) strong diffuse immunoreactivity for GFAP on GFAP immunohistochemical staining (magnification, x100), where the negatively stained areas consist of blood vessels exhibiting exuberant microvascular proliferation.

Figure 3.

Case 3: Contrast-enhanced magnetic resonance imaging (MRI) of the (A) lumbar spine sagittal and (B) axial sequences reveal intradural spinal metastasis of glioblastoma to the L5-S1 region. Contrast-enhanced MRI of the (C) brain axial, (D) sagittal and (E) coronal sequences show the primary intracranial glioblastoma that was discovered subsequent to the metastatic intradural lumbar spinal lesion.