I. Overview
Brain metastasis is the most serious complication of tumors in all systems and is also a common brain tumor in adults.
Epidemiology
(1) According to different sites, they can be divided into cranial, dural, soft meningeal and intracerebral parenchymal metastases, with the latter two accounting for more than 80%.
(2) Most brain metastases come from lung cancer (about 50%), melanoma, kidney cancer, rectal cancer, soft tissue sarcoma, breast cancer and non-Hodgkin’s lymphoma.
(3) The metastatic sites are brain, cerebellum and brainstem in order, with multiple cases accounting for more than 50%.
(4) The peak incidence is between the ages of less than 10 and 55-59.
(5) Typical metastases are 6 months to 2 years after the diagnosis of the primary tumor.
III. Pathophysiology
(1) Metastases are mainly disseminated via blood stream, and a few are disseminated from intra-spinal or orbital tumors via subarachnoid space; metastases can synthesize and secrete pro-angiogenic substances, which cause neovascularization within the tumor and form an open blood-brain barrier locally; renal parenchymal tumors often metastasize to the choroid plexus of the lateral ventricle, and thyroid and breast cancers tend to metastasize cranially.
(2) There are two ways for tumors to spread to the skull via blood flow: most of them spread via arterial circulation, very few pelvic or gastrointestinal tumors can enter the skull through Batson’s plexus, so the emboli that enter the skull via arteries mainly originate from primary lung cancer or metastatic lung cancer; single cancer cells can enter the arterial blood flow through pulmonary capillaries to form metastases, and large tumor emboli can enter the arterial blood flow through the oval foramen in the left and right chambers of the heart directly Large tumor emboli can enter the arterial circulation through the ostium of the left and right chambers of the heart and metastasize to the skull.
(3) The basic process of metastasis is the shedding of tumor cells from the primary foci as the first link to form metastasis, followed by the migration and invasion of shed cells, entering the blood circulation, “capture” of tumor cells by target organs, and the formation of metastases.
Pathology
(1) Most brain metastases appear as well-defined spherical or nodular lesions, mostly located at the gray-white matter junction, with uneven texture, often with intratumoral necrosis, cystic changes and hemorrhage, and blood supply is usually not abundant.
(2) A few are diffuse, often coexisting with nodular lesions, and may involve the dura, arachnoid, and soft meninges, with extensive dural thickening and multiple, scattered punctate lesions on the brain surface, with extensive tumor cell infiltration seen microscopically.
(3) It can cause cerebral infarction due to arterial embolism, and it can cause intracranial infection due to bacteria carried by those who originate from lung cancer.
V. Clinical manifestations
The clinical manifestations vary according to the size, number and location of tumor. Generally, the course of the disease is short and progresses rapidly; the symptoms of cranial hypertension caused by intracranial occupancy or edema are the most common; the cerebrospinal fluid circulation obstruction caused by metastasis in the posterior cranial fossa is common in subacute or acute onset.
VI. Diagnosis and auxiliary examinations
(1) Osteolytic destruction in the form of phagocytosis can be seen on cranial X-ray plain film.
(2) CT scan shows hypodensity or isodensity (high density for metastatic lymphoma), and there may be cystic lesions surrounded by obvious finger-like distribution of hypodense edema bands; after enhancement, it shows irregular thick-walled, annular enhancement with nodules or regular, uniform thin-walled enhancement, with intracranial metastases of choriocapillary epithelial cell carcinoma, melanoma, thyroid cancer deteriorating adrenal cancer enhancing most obviously.
(3) MRI scan is long T1 and long T2 signal on flat scan, similar to gray matter; the T2 signal of edema is significantly higher than that of tumor; it can show intra-tumor hemorrhage not contemporaneously.
(4) PET helps to distinguish the malignancy of the tumor, identify recurrent tumors from post-radiation or post-chemotherapy necrosis and postoperative changes.
(5) Laboratory examination of cerebrospinal fluid exfoliation cytology helps to clarify whether there is soft meningeal involvement, and tumor marker examination helps to determine the source of metastasis.
VII. Differential diagnosis
(1) Primary tumor glioma mostly occurs in the white matter of the brain, rarely multiple, with mild peritumor edema and no history of other tumors; meningioma is located outside the brain, closely related to the dura or ventricles, uniformly enhanced, and necrosis is rare.
(2) Brain abscesses mostly have obvious history of infection or heart disease, without history of tumor.
(3) Cerebral hemorrhage and cerebral infarction infarct foci are often distributed along the blood flow supply, with light local occupying effect and insignificant enhancement.
VIII. Treatment
(1) symptomatic treatment anti-seizure; mannitol, steroid hormones help to reduce edema, improve the quality of survival and prolong the survival period.
(2) Etiological treatment is mostly local treatment (surgery or radiosurgery) combined with whole brain radiation (WBR).
①Surgical treatment is suitable for those whose primary site is not clear, whose primary site is clear but the nature of intracranial lesion is not clear (e.g. breast cancer combined with meningioma), whose primary tumor has been controlled but there is a single intracranial metastasis, and whose primary tumor is not controlled but the symptoms caused by metastasis are obvious and can be easily removed by surgery.
②Radiation therapy is used for multiple metastases; those with poor general condition, rapid progression of primary tumor and KPS <70 scores are treated with simple wbr; those with more stable condition and kps >70 scores are considered for WBR when recurrence or new lesions appear after surgery or radiosurgery, mostly with 20Gy/5 times, or 30Gy/10 times, or 40Gy/20 times (for those whose expected survival may exceed 1 year); also Stereotactic radiosurgery can be used according to the situation.
(iii) The role of systemic chemotherapy for brain metastases is unclear, but it is effective for some recurrent metastases such as small cell carcinoma, breast cancer, germ cell tumor and non-Hodgkin’s lymphoma.
IX. Prognosis
It is mainly related to the degree of progression of the primary disease, the patient’s KPS score (70), the number and location of metastases, and the patient’s age (60 years). The previous experience of the Department of Neurosurgery of Peking University People’s Hospital is that brain metastases are often the first lesions that endanger patients’ lives regardless of the primary site, and therefore whether brain metastases are actively managed is a key factor in determining patients’ survival.