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Introduction: Glioblastoma (GBM) is a devastating disease with poor overall survival. Despite the common occurrence of GBM among primary brain tumors, metastatic disease is rare. Our goal was to perform a systematic literature review on GBM with osseous metastases and understand the rate of metastasis to the vertebral column as compared to the remainder of the skeleton, and how this histology would fit into our current paradigm of treatment for bone metastases. Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant literature search was performed using the PubMed database from 1952 to 2021. Search terms included "GBM", "glioblastoma", "high-grade glioma", "bone metastasis", and "bone metastases". Results: Of 659 studies initially identified, 67 articles were included in the current review. From these 67 articles, a total of 92 distinct patient case presentations of metastatic glioblastoma to bone were identified. Of these cases, 58 (63%) involved the vertebral column while the remainder involved lesions within the skull, sternum, rib cage, and appendicular skeleton. Conclusion: Metastatic dissemination of GBM to bone occurs. While the true incidence is unknown, workup for metastatic disease, especially involving the spinal column, is warranted in symptomatic patients. Lastly, management of patients with GBM vertebral column metastases can follow the International Spine Oncology Consortium two-step multidisciplinary algorithm for the management of spinal metastases. [ABSTRACT FROM AUTHOR]

Background: Intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC) often shows extracranial metastasis, and treatment options are very limited. Immune-checkpoint molecules have not been studied well in SFT/HPCs, and their role in intracranial SFT/HPCs remains unclear.Methods: We investigated the expression of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and tumor-infiltrating lymphocytes (TIL) in 16 patients of intracranial SFT/HPC by immunohistochemistry to determine if correlation with prognosis exists.Results: Median overall survival (OS) of 16 patients was 9.2 years, and median follow-up of alive patients was 9.9 years. Recurrence was observed in 13 (81.3%) patients, and extracranial metastasis were observed in 6 (37.5%). PD-L1 expression was observed in all 16 tumors, whereas PD-1 expression was observed in 2. CD3 and CD8 expressions were observed in TILs in 12 and 13 patients respectively. Although the ratio of PD-L1 positive-tumor cells was not associated with OS, progression-free survival, or metastasis-free survival (MFS), diffuse staining of PD-L1 showed a trend toward shorter time to treatment failure (TTF: time to either extracranial metastasis or death) (p = 0.072). Similarly, the intense staining of PD-L1 was associated with shorter MFS (p = 0.0084) and TTF (p = 0.033). CD3 or CD8 expression was not associated with any of the prognostic parameters. In the combined analysis of PD-L1 and CD8, diffuse PD-L1 staining coupled with no or sparse CD8 expression was significantly associated with a shorter TTF (p = 0.005) and showed a trend toward shorter MFS (p = 0.0611).Conclusions: PD-L1 is frequently expressed in intracranial SFT/HPCs, and diffuse or intense PD-L1 expression might be associated with the early occurrence of extracranial metastases. [ABSTRACT FROM AUTHOR]

This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER−, 36 % progesterone receptor (PR)+, 34 % PR−, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2−, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the following: whole brain radiation therapy (52 %), chemotherapy (51 %), stereotactic radiosurgery (20 %), surgical resection (14 %), trastuzumab (39 %) for HER2 positive tumors, and hormonal therapy (34 %) for ER and/or PR positive tumors. Factors that had an impact on prognosis included grade and size of the tumor, multiple metastases, presence of extra-cranial metastasis, triple negative or HER2+ biomarker status, and high Karnovsky score. Novel therapies such as application of agents to reduce tumor angiogenesis or alter permeability of the blood brain barrier are being explored with preliminary results suggesting a potential to improve survival after brain metastasis. Other potential therapies based on genetic alterations in the tumor and the microenvironment in the brain are being investigated; these are briefly discussed. [ABSTRACT FROM AUTHOR]

Extracranial metastasis is a unique but rare manifestation of glioblastoma multiforme. It is thought to arise from glioblastoma cells disseminated into the blood stream. We undertook a comprehensive analysis of 88 cases of extracranial glioblastoma (5 were gliosarcomas) published between 1928 and 2009. Cases included in the analysis were primary or secondary glioblastomas that subsequently invaded organs outside the brain or spinal cord. The median age was 38 years and the median overall survival time was 10.5 months (range 0.0-60.0 months). The median time from symptom onset to diagnosis of primary glioblastoma was 2.5 months, from diagnosis to detection of extracranial metastasis was 8.5 months, and from metastasis to death was 1.5 months. From 1940 to 2009, there has been progressive lengthening of the interval from detection of extracranial metastasis to death, at a rate of 0.7 months per decade (95% confidence interval 0.5-1.0 month). Use of magnetic resonance imaging correlates with an increase in overall survival but not age, gender, or site of primary glioblastoma. Patients treated with surgery + radiation + chemotherapy + cerebrospinal fluid shunting had the longest average survival interval from metastasis to death when compared to those treated with surgery alone, radiation alone, surgery + radiation, and surgery + radiation + chemotherapy. Lung metastasis is a prognostic factor of extremely poor outcomes. We conclude that patients with glioblastoma extracranial metastasis have poor prognosis, but there has been a progressive lengthening of survival in each successive decade from 1940 to 2000. [ABSTRACT FROM AUTHOR]

Extracranial metastases and their frequency by sites have been described as prognostic factors for survival of patients with brain metastasis. However, these factors must be identified and described in more detail for a large series of patients. Using routine data from the largest German health insurance fund, 5,074 patients with brain metastasis who were diagnosed and treated in 2008 were analyzed to identify the frequency and distribution of extracranial metastatic sites concurrent with brain metastasis in relation to age, gender, and tumor type. Brain metastases were observed in males more frequently than in females (56.4 and 43.6% respectively P < 0.001), and were most often from lung (51.2%), breast (12.3%), and unknown (7.5%) primaries. Extracranial metastatic sites were observed in 58.8% of patients; the number of sites was from 1 to 7, with a mean of 1.11. For the 16 most common primary sites the range was from 0.13 to 1.91 . In 11 of these 16 sites, lungs were the most common concurrent metastatic site. Lung cancer, breast cancer, non-Hodgkin's lymphoma, and testicular cancer most commonly metastasized to bone, and bladder cancer to kidneys. Different primary tumors have different frequencies and patterns of extracranial metastatic sites concurrently with brain metastasis. The lung is the most common metastatic site of most primary tumors, bone for a few tumors, and kidneys for bladder cancer. For the unknown primary tumor type, screening for these most common metastatic sites must be intensified, in particular when molecular assessment is not available. [ABSTRACT FROM AUTHOR]

Extracranial metastasis of glioblastoma multiforme (GBM) is very rare, in spite of very aggressive tumor behavior and being documented in only a few patients. In this article we present a 25-year-old man with secondary glioblastoma associated with extracranial progression and distant metastasis. He was diagnosed by magnetic resononce (MR) with an intracranial lesion in the right parietofrontal region, which was subsequently resected. Histology revealed a diffuse astrocytoma (grade II). The tumor recurred 1 year later and the patient received a second craniotomy. A diagnosis of GBM was made. After radiotherapy, he presented with right cervical lymph node metastases. The cytomorphological features supported a diagnosis of metastatic glioblastoma multiforme. The neck dissection was made and histology confirmed the fine needle aspiration diagnosis of glioblastoma multiforme. MR with diffusion-weighted imaging revealed right cervical lymph node metastases and multi-bone metastases (mainly pelvic bone) 3 weeks later. [ABSTRACT FROM AUTHOR]