Metastatic glioblastoma

Last revised by Anthony Liu on 7 Jan 2023

Metastatic glioblastoma is a rare progression of glioblastoma, with an incidence of 0.4-0.5% of all glioblastoma cases. The locations can be extraneural, such as leptomeninges and dural venous sinuses, or both extraneural and extracranial, such as solid organs and lymph nodes.

In a recent case series in the United States, the top five regions of metastases in order of frequencies are bone, lymph node (thoracic and cervical), lung, leptomeninges, and soft tissue 1.

The median time from diagnosis of the primary glioblastoma to metastasis and from detection of metastasis to death was 8.5 months and 1.5 months, respectively. Patients with lung metastases carry the worst prognosis 2.

Male gender, young age, and proximity to the ventricular system are identified as risk factors for metastasis 3.

Clinical presentation usually depends on the site of metastasis. These include pathological fractures or spinal cord compression for bone or vertebral metastases, dyspnea or hemoptysis for lung metastases, and transaminitis for hepatic metastases.

Diagnosis is confirmed by histology when the microscopic features and immunohistochemistry are typical of a glioblastoma. However, this is sometimes difficult in tumors that are poorly differentiated and thus do not express glial markers.

Given the lack of lymphatic system in the brain, glioblastoma cells seed either haematologically, or through surgical procedures that introduces malignant cells into the abdomen (ventriculoperitoneal shunts) or dural or scalp lymphatics 1. The lack of lymphatic system may also contribute to the rarity of metastatic glioblastoma, as well as other factors such as the presence of the blood-brain barrier and short overall survival 4.

Most of the patients described in the literature have IDH-wildtype glioblastoma (primary glioblastoma), but a small pool of younger patients have metastatic secondary glioblastoma, suggested by the presence of IDH1/2 or RB1 alternations 1.

Radiographic features of metastatic glioblastoma to other body systems (bone, vertebral, pulmonary, hepatic) are similar to other primary tumors.

Osteolytic changes are often seen in the spine and pelvis, sometimes with associated pathological fracture and loss of vertebral height.

Singular or multifocal soft tissue nodules in the lungs, with occasional thoracic lymphadenopathy 1.

Majority of the literature describes a low number of metastatic foci in the liver. These lesions are usually hypodense to the liver parenchyma. However, one case report described miliary metastases of glioblastoma in the liver 4.

MRI is more sensitive in detecting metastases, and helps in characterizing vertebral and hepatic lesions. It can also demonstrate spinal cord compression when it is suspected.

Interestingly, survival in metastatic glioblastoma is not significantly worse than non-metastatic glioblastoma 2. However, diagnosis of metastatic glioblastoma is often made in the last months of life with limited treatment options available. The only therapy that may have survival benefit is systemic chemotherapy (e.g., temozolomide or bevacizumab), however the efficacy data is scarce due to the rarity of the tumor.

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Cases and figures

  • Metastatic extraneural glioblastoma
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  • Metastatic extraneural glioblastoma
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