Chordoma originates from the embryonic remnants of the notochordal tissue. During the embryonic period, the upper end of the notochord is found in the pterygoid and occipital bones at the base of the skull, partially reaching the intracranial surface and articulating with the dura above the pterygoid saddle, partially reaching below the occipital bone (i.e., the linguopharyngeal surface), and partially between the skull base and the pharyngeal wall. The lower end of the spinal cord is located in the central and paracentral parts of the sacrococcygeal region. Therefore, chordoma is most common in these areas, especially in the pterygo-occipital and sacrococcygeal areas of the skull base, followed by the spinal type. The most common type, also known as the typical type, accounts for 80%-85% of the total number of cases. There is no cartilage or other mesenchymal components in the tumor. It is mostly seen in patients aged 40 to 50 years old, and is rare in those younger than 20 years old. There is no gender difference. Pathologically there can be several growth patterns, but lamellar growth is characteristic, consisting of vacuolated epithelial cells and mucus stroma. Immunostaining for cytokeratin and epithelial membrane antigens is positive, and nucleated grains are seen by electron microscopy. These features help to distinguish this disease from chondrosarcoma, which has negative immunostaining and no nucleoli on electron microscopy. Chondrooid chordoma accounts for 5% to 15% of chordomas. The microscopic features include more or less clear cartilage-like areas in addition to those typically seen above. Although some authors have classified it as a low-grade malignant chondrosarcoma by electron microscopy, numerous immunohistochemical studies have found positive reactions for epithelial marker antigens in chondrooid chordomas. This type has a younger age of onset and was previously thought to have a generally better prognosis than the common type, but both are now considered to have a similar prognosis. Mesenchymal type, also known as atypical type, accounts for 10% of chordoma and contains both common and malignant mesenchymal components, which microscopically appear as actively proliferating tumors with significantly reduced mucus content and nuclear schizophrenia. A small number of tumors may metastasize via the blood stream and disseminate via the subarachnoid space. This type of tumor can be secondary to conventional radiotherapy or malignant. It often dies 6 to 12 months after diagnosis. II. Pathogenesis When the fetus develops to 3 months of age the notochord begins to degenerate and disappear, leaving only the residual in the intervertebral disc, the so-called nucleus pulposus. If the embryonic residue of the spinal cord stays in the above mentioned area until after birth, it may gradually evolve into a tumor. Clinical manifestations Intracranial chordoma is a benign tumor with slow growth and a long course, averaging more than 3 years Headache is the most common symptom, about 70% of patients have headache, sometimes for several years before seeking medical attention. The headache is persistent and dull in nature and does not change significantly throughout the day. Headaches in chordoma are associated with a slow and persistent infiltration of the skull base, and headaches can recur. The clinical manifestations of intracranial chordoma can vary depending on the site of the tumor and the direction of tumor development. 1.Saddle chordoma Hypopituitarism is mainly manifested by impotence, amenorrhea and body fatness. Optic nerve compression produces primary optic nerve atrophy, loss of vision and bilateral temporal hemianopia, etc. 2. Parasympathetic chordoma mainly manifests in III, IV and VI cerebral nerve palsy, among which abduction is more common, probably because of the long stroke of the abduction nerve and the fact that the proximal end of the abduction nerve is often the site of origin of the tumor, resulting in a higher incidence. This may be due to the long stroke of the adductor nerve. Cerebral nerve palsy can be bilateral, but is often unilateral and, incomprehensibly, often on the left side. The main manifestations of chordoma of the slope are brainstem compression symptoms, i.e., walking disorders, cone bundle signs, and VI and VII cerebral nerve disorders, of which bilateral spinal nerve damage is characteristic. The lesion is widespread and extends beyond one of the above types, even to the skull base displacement area, with the clinical symptoms and imaging manifestations of the above related types. 5.Complications As the tumor occurs in the skull base, it may cause traffic hydrocephalus. If the tumor develops to the pontocerebellar horn, hearing impairment, tinnitus and vertigo will occur. Chordoma originates near the nasopharyngeal wall and often protrudes into the nasopharynx or infiltrates one or more paranasal sinuses. It causes nasal inability to ventilate, obstruction, pain, and commonly purulent or bloody nasal discharge, also due to mechanical obstruction, causing difficulty in swallowing. Nasopharyngeal symptoms often appear before nerve involvement, and it must be kept in mind that there is a 13% to 33% chance of seeing a mass in the nasopharyngeal cavity. The diagnosis and differential diagnosis of chordoma should be considered in adult patients with a long history of headache and paralysis of one side of the spinal nerve, but the diagnosis needs to be determined with the help of X-ray, CT and MRI imaging. Chordoma should be differentiated from meningioma. DSA commonly shows thickening of the meningeal blood supply arteries with significant tumor staining. If chordoma grows into the posterior cranial fossa, it should be differentiated from an auditory neuroma in the pontocerebellar horn. MRI is often useful for differential diagnosis. Chordoma in the saddle area needs to be differentiated from pituitary adenoma and craniopharyngioma. The latter two tend not to cause extensive bone destruction at the skull base. Pituitary adenomas generally appear on imaging as enlarged involvement of the pterygoid saddle, deepening of the saddle base, and bone resorption. Craniopharyngioma is usually seen on CT with arcuate or eggshell calcifications in the cyst wall, and usually does not cause adjacent bone destruction. Chordoma that grows downward into the nasopharynx is similar to nasopharyngeal carcinoma that metastasizes to the skull base because of its clinical manifestations and radiographic features, and the differential diagnosis mainly relies on nasopharyngeal puncture biopsy. Immunohistochemical staining is helpful, as chordoma is positive for a variety of tissue markers, such as Cyto-K6/7 EMA7/7, CEA6/7, GFAP0/7, Des0/7, α-AT7/7, Lyso4/7, whereas chondrosarcoma is negative. V. Treatment Surgical treatment The anatomical location of chordoma is deep, which makes surgical exposure difficult, coupled with the insidious onset and long course of the disease, the tumor has already invaded the skull base extensively when the patient comes to the clinic. Because chordoma is insensitive to radiation, conventional radiotherapy is usually only palliative, and the long-term efficacy of radiosurgery remains unclear, therefore, endoscopic surgery of the skull base through the nasal and/or oral approach is still the main treatment for this disease. Radiosurgery treatment includes gamma-knife, proton-knife and X-ray-knife. In particular, proton knife can be treated by high-dose segmentation, combining the advantages of radiosurgery and conventional radiotherapy, showing safety and effectiveness for residual tumors in neurovascularly important areas after surgery. Other treatments Include thermal therapy, 90Y local burial therapy and chemotherapy, but the efficacy is uncertain. Drug therapy Chemotherapeutic drugs have been considered to have no significant therapeutic effect on chordoma: in recent years, targeted drugs have been reported in the foreign literature for the treatment of chordoma. Targeted therapy for chordoma may have good therapeutic prospects. It is histologically benign, but has the following malignant features: deep location, easy to invade the skull and brain and important neurovascular; infiltrative growth, mostly without obvious envelope; occasional metastasis; not easy to completely resect, postoperative recurrence is close to 100%; most patients die several years after diagnosis. Thus, once diagnosed, chordoma of the skull base should be treated as a malignant tumor. The survival rate of skull base chordoma in early reports at home and abroad is generally low, and the 5-year survival rate is maintained at 30%-40%. In recent years, there has been a gradual increase in the number of reports from home and abroad, and the postoperative survival rate of skull base chordoma has improved significantly, maintaining a 5-year survival rate of 60%-70%.