The conventional wisdom is that primary brain tumors do not metastasize to distant sites. However, in fact, since 1928 there have been continuous reports of distant metastasis of primary brain tumors, the vast majority of which are gliomas. In recent years, metastasis of gliomas has attracted the attention of some scholars. This article reviews the reports and research status of distant metastasis of gliomas in recent years. I. Characteristics of distant metastasis of cerebral gliomas In 1926, Bailey and Cushing pointed out that primary brain tumors do not metastasize to distant places outside the neuraxis. However, in 1928, Davis reported for the first time a case of glioblastoma multiforme metastasizing to both lungs and soft tissues after craniotomy. Subsequently, distant metastases of gliomas were reported, but all occurred after surgery, and in 1959, Rubinstein reported the first case of medulloblastoma with distant metastases without previous surgery, and in 1967, Rubinstein reported a case of astrocytoma with distant metastases without previous surgery. By 1981, 12 cases of distant metastases from oligodendrogliomas had been reported, and in 1995, Rawat reviewed 79 cases of extracranial metastases from benign meningiomas.In 1995, Huang reviewed 247 cases of glioblastoma multiforme with extracranial metastases. It has been reported that the most frequent distant metastases among CNS tumors are: glioblastoma multiforme, meningioma, and medulloblastoma, in that order. Data show that with the advancement of therapeutic methods and techniques, improvement of efficacy, and prolongation of patient survival, reports of distant metastasis of primary brain tumors, the vast majority of which are gliomas, have gradually increased [1-9]. In 1955, Weiss proposed the diagnostic criteria for primary brain tumor metastasis outside the central nervous system, including: ① the histological characteristics of the metastatic foci are consistent with central nervous system tumors; ② the first symptoms are caused by central nervous system tumors; ③ biopsy excludes primary tumors from other parts of the body; and ④ the morphological characteristics of the primary foci and the metastatic foci must be completely compatible. However, in 1974, Dolman reported a case of glioblastoma with lymph node metastasis as the first clinical manifestation, since then ② in Weiss diagnostic criteria was rejected, and ①, ③, ④ as the diagnostic criteria of primary brain tumor metastasis to the off-axis of the neuraxis has been widely accepted. The incidence of distant metastasis of gliomas varies from report to report, ranging from 0.4% to 2.3%. The interval between initial detection of glioma and the development of distant metastases has been reported to be as long as 17 years and as short as a few days, with an average of 22.1 months [1,2]. The majority of glioma metastases occur after craniotomy or cerebrospinal fluid shunt. Literature shows that 96% of extracranial distant metastases are related to surgery, and distant metastases occurring without previous surgery account for only 8.5%-11% of all cases of distant metastases from primary brain tumors, ranging from 4%-6% in children to about 11% in adults [1,2,6,7].Rickert reported that 27.3% of the 245 cases were directly related to the shunt surgery [2], and the following are commonly seen germ cell tumors (33.3% of cases and 22.7% of germ cell tumors alone), glioblastomas (10.6%), yolk sac tumors (7.6%), and hairy cell astrocytomas (6.1%). Medulloblastoma, on the other hand, was most often seen as a metastasis unrelated to shunt surgery (69.4%). Extracranial metastases occur in 0%-4.3% of glioblastomas treated with interstitial radiotherapy [11].Dawson states that the more surgery a patient with a glioma undergoes, the greater the likelihood of distant metastases. Some scholars believe that craniotomy destroys the natural protective system of the brain, making it easy for tumor cells to enter the meninges and vertebral venous system, and subsequently enter the abdominal cavity and portal venous system and its accompanying lymphatic system. It has been suggested that both surgery and radiation therapy can promote glioma metastasis. There is controversy about whether cerebrospinal fluid shunt surgery increases the chance of glioma metastasis. Although several cases of gliomas metastasizing to abdominal organs after ventriculo-peritoneal shunt surgery have been reported, there have also been reports of patients with medulloblastoma who underwent preoperative ventriculo-peritoneal shunts developing metastases to other sites postoperatively without involvement of the peritoneum. Shunt surgery, undergoing multiple craniotomies, and long survival have been cited as predisposing factors for the development of extracranial distant metastases from gliomas. The route of extracranial distant metastasis of gliomas to the cerebrospinal tract is currently unknown. Although the incidence of cerebrospinal fluid (CSF) dissemination of primary brain tumors is only 5-9%, CSF is still considered to be the main route of metastasis for gliomas, especially for medulloblastomas and oligodendrocytomas. However, some scholars believe that medulloblastoma is mainly hematogenous metastasis. There are many claims about the reasons for the low incidence of extracranial metastasis of gliomas, such as the lack of lymphatic system within the skull; blood-brain barrier and blood-cerebrospinal fluid barrier; intracranial veins or venous sinuses are prone to collapse or occlusion due to intracranial high pressure or tumor compression; neuroglial cells are only adapted to intracranial survival; special metabolic needs of the tumor cells; glioma patients with a short survival period die before metastasis occurs; and intracranial environment is stable and Relatively little chance of being subjected to compression and trauma. Among them, short survival is considered by most scholars as one of the main reasons why distant metastasis of glioma is rare. In fact, with the advancement of glioma treatment and prolonged survival of patients, reports of distant metastasis of gliomas are indeed on the rise. In addition, the role of the blood-brain barrier has been emphasized by some scholars. In addition, it is interesting to note that Wiendl reported the first case of “ectopic” ventricular meningioma originating in the liver in 2003 [10], suggesting: can gliomas occur independently in other extracranial organs? Are gliomas unique to the central nervous system? Subclinical metastasis of gliomas Based on the understanding that primary brain tumors do not metastasize to extracranial areas and the shortage of transplant donors, patients with primary brain tumors have been included in the scope of organ transplant donors in the past. However, in recent years, there have been reports of transplant recipients who have been found to have the same type of glioma growth in the transplanted organ (kidney, liver, heart, etc.) after transplantation of organs from patients with glioma, and the possibility of patients with primary brain tumors being used as donors for organ transplantation has become a subject of controversy. In 1994, a lung transplant recipient died of glioblastoma multiforme after the discovery of glioblastoma multiforme in the mediastinal lymph nodes following transplantation of lungs from a patient with glioblastoma multiforme.In 1999, it was reported that after transplantation of organs from patients with primary brain tumors in 54 organ transplant recipients, tumors of the same nature as the primary brain tumors were found in the transplanted organs in 9 cases, and these tumors did not regrow. In 2001, Schiff reported that 6 transplant recipients with gliomas had the same type of gliomas, 5 of which were glioblastoma multiforme and 1 of which was oligodendroglioma, in their transplanted organs. In 2003, Buell et al. reported 12 cases of organ transplant recipients who, after transplantation of organs from patients with primary brain tumors, were found to have the same type of tumor growth within the transplanted organs, including 8 cases of glioblastoma multiforme, 1 case of astrocytoma, and 3 cases of medulloblastoma.Buell classified the high degree of malignancy, history of surgery, radiation therapy, and systemic chemotherapy as the presence of brain gliomas accompanying the transplanted organs from the Buell listed high malignancy, history of surgery, radiation therapy, and systemic chemotherapy as four risk factors for gliomas to metastasize from the donor to the recipient and to grow in the transplanted organ. The chance of tumor metastasis in those without risk factors was 7%, and the chance of tumor metastasis with the transplanted organ in those who possessed one or more of these risk factors was 53%. From 1987 to 2003, there have been 31 cases in which organ transplant recipients who were transplanted with organs from patients with gliomas were found to have the same type of glioma growth in the transplanted organs, and these tumors did not re-disseminate into the recipient’s brain parenchyma [12-14]. Therefore, it has been suggested that micrometastases of gliomas in other organs within the patient’s body may be more common than clinically estimated and that subclinical metastases of gliomas may be underestimated! Third, the prognosis of distant metastasis of glioma Although the incidence of metastasis of glioma is low, it seriously affects the survival and prognosis of patients.In 1976, Roberta and German reported that the median survival of 50 patients with oligodendrogliomas without distant metastasis was 8.5 years, while the median survival of those with distant metastasis was only 32 months.In 1980, Pasquier reviewed 72 cases of In 1980, Pasquier reviewed 72 cases of glioma patients with distant metastasis, and the mortality rate within 2 years was 82.8%. 2003, Buell reported that the mortality rate of 12 recipients with glioma metastasis in the transplanted organs after organ transplantation was 75%. Experimental studies on distant metastasis of gliomas Experimental studies on distant metastasis of gliomas have rarely been reported. 1996, Chen Sangu et al. injected glioma cell suspension into the peritoneal cavity of nude mice to form metastatic foci of gliomas in the lungs. 2003, Bohm et al. reported that PCR was used to detect GFAP mRNA in blood in order to find out whether there were tumor cells in the blood of patients with gliomas and the results showed that 10 cases of astrocytes were detected and the results showed that there were no tumor cells in the blood of patients with astrocytomas. GFAPmRNA was not detected in the peripheral venous blood of the 10 astrocytoma and 10 glioblastoma patients tested, so it was proposed that subclinical metastasis of gliomas is extremely rare and may be limited to certain specific types of gliomas [15]. However, this study has the following shortcomings: the sample size is too small; peripheral venous blood was taken only during surgery, with a single time point, lack of dynamic monitoring, and greater chance; and GFAP-negative glioma cells could not be detected. Therefore, the conclusions of this study are not yet convincing enough.In 2004, WangM et al. studied a case of oligodendroglioma with multiple bone metastases and found that heterozygous deletion of 1p19q was helpful in the diagnosis of extracranial metastasis of oligodendroglioma [16].