Chordoma is a relatively rare tumor that grows slowly and aggressively and can occur on the slope of the skull base, in the saddle area, or in the sacrococcygeal region of the spine. The notochordal structures appear during the fourth week of human embryonic development, and as the embryo develops, the notochord gradually degenerates, but some of the notochordal tissue located in the pterygo-occipital region of the skull base and the sacrococcygeal region of the spine remains incompletely degenerated. Current authors believe that this residual tissue is affected by certain conditions, such as stimulation, trauma or increased hormone levels (e.g., human I? chorionic gonadotropin, etc.) may induce tumorigenic proliferation and the formation of chordoma. Epidemiology Chordomas can occur at any age and can range from 1 1/2 to over 80 years of age, but most tumors occur around the age of 40, with our own data showing that they occur primarily between 30 and 40 years of age. Chordoma of the skull base is rare, accounting for only 0.1% to 0.2% of intracranial tumors. Etiology and pathology Most tumors derived from embryonic remnants often occur in adolescents, and the age at which chordomas tend to occur is difficult to explain by the embryonic remnant theory alone. In recent years, many new insights into the development of chordoma have been proposed, including the tumor stem cell theory by Miettinen et al. who suggested that some cells in the chordal tissue have changed their differentiation pathway or that new malignant cell populations appear locally in the tumorigenesis. The karyotype analysis of tumor cells showed abnormal cytosolic chromosome structure. In a cytogenetic study of chordoma, Scheil et al. observed the chromosomal profile of this tumor cell using in situ hybridization and found that loss of chromosome lp and 3p loci was associated with the development of chordoma and concluded that highly specific genetic studies are a useful tool to further explain the oncogenetics and molecular genetics of chordogenesis. The tumor is grayish-brown in color, uneven in texture, either brittle or soft, translucent and jelly-like, with abundant mucus and blood supply, and some of the tumor tissue is mixed with bony components and multiple bony compartments are visible. Some tumors have irregular margins and adhere to surrounding tissues, and some cranial nerves are wrapped by tumors. The tumor is of different sizes and grows chronically and aggressively, and can have extracranial distant metastases. Chordomas that occur in childhood grow faster and are more likely to metastasize because they are less differentiated and have a more malignant histology than those that occur in adults. Histopathologic examination shows the morphologic features of benign or low-grade malignant tumors, such as a general uniformity of cell size, abundant cytoplasm, relatively regular nuclei, and rare nuclear fission images. The histopathology of chordoma is divided into three subtypes under light microscopy: normal chordoma, chondroid chordoma, and hypofractionated chordoma. The common type of chordoma is slow growing, soft, and rich in blood supply with localized hemorrhage; the hypodifferentiated chordoma is a bifurcated tumor with rapid growth and typical chordoma structures as well as sarcoma-like structures in the tumor tissue. Under light microscopy, the chordoma cells are in the form of clusters or cords, and there are three types of cell morphology: (1) most tumor cells are large, round or polygonal in shape, characteristic of epithelial cells, with abundant cytoplasm, mucus and a large number of vacuoles, regular nuclei, often with abundant chromatin, and a large amount of mucus scattered in the interstitium. ②Cells are island-shaped distribution of chondrocyte-like cell components. (iii) The cells are astrocytic or long spindle-shaped, with tightly arranged cells, few or no intracytoplasmic vacuoles, mildly heterogeneous nuclei, mildly increased heterochromatin in the nucleus, less interstitial mucus, sarcomatoid changes, and chronic inflammatory cell infiltration. Most chordomas present with a predominance of vacuolated cells. It is generally accepted that more mucus in the interstitium of chordoma indicates better differentiation of the tumor, while less mucus in the interstitium and tougher tumor tissue indicates a relatively high degree of malignancy. According to the origin and development of the tumor, chordoma of the skull base is divided into saddle type, middle cranial fossa type, slope – posterior cranial fossa type, nasopharyngeal type and mixed type. Clinical manifestations The clinical symptoms of patients are complex, mainly manifested by headache and visual disturbance. Persistent dull headache is associated with prolonged infiltration and destruction of the skull base bone by the tumor. Other symptoms such as dysphagia, choking and coughing, slurred speech, poor diction, blurred vision, unstable walking, facial nerve palsy, and deafness are related to the damage of adjacent cranial nerves by tumor tissue. On neurological examination, patients may have signs such as blunted gag reflex, hypoesthesia, ptosis, limited eye movements, horizontal nystagmus, proptosis, and lingual tremor. Chordoma in the saddle area often involves the optic pathway and pituitary gland, resulting in visual field loss and hypotony, and some patients have hypopituitarism and some have subthalamic involvement. The main manifestation of cranial fossa tumors is III-VI cranial nerve palsy, especially abducens nerve palsy, which may be related to the long stroke of this nerve and its entry into the cavernous sinus, which is the origin of most chordomas. The cavernous sinus syndrome may occur when the tumor compresses or invades the cavernous sinus. Slope-posterior cranial fossa tumors often have bilateral cone bundle signs, nystagmus, ataxia, and cranial nerve palsy. Those that progress to the pontocerebellar horn of the cerebellum present with V-VIII cranial nerve symptoms. If the jugular foramen area is involved, posterior group cranial nerve palsy is present. Nasal (oropharyngeal) tumors often cause symptoms such as nasal congestion, nasal maggots, hypopharyngeal and ventilation difficulties, and swelling may be seen on examination of the nasal (oropharyngeal) cavity. Mixed type tumors are huge and involve a wide range of areas, and may show corresponding symptoms and signs depending on the involved areas. The tumor may be irregular, lobulated or nodular in shape, with eggshell-like calcification at the edge of the tumor and different degrees of bone destruction around the lesion on CT scan. Diagnosis and differential diagnosis Based on the clinical manifestations such as slow onset, long course, multiple cranial nerve damage, combined with the location of the tumor, obvious bone destruction and CT, MRI and other imaging findings, the diagnosis of chordoma is mostly not difficult. Although it is sometimes necessary to differentiate it from pituitary tumor, meningioma and nerve sheath tumor, these tumors rarely cause extensive bone destruction in the sloping saddle area like chordoma, except for aggressive pituitary tumor. What is more difficult is to differentiate them from nasopharyngeal carcinoma, cartilaginous tumors of the skull base, and giant cell tumors. In particular, chondrosarcoma is so similar to chordoma in origin, clinical and imaging presentation, and pathologic features that some scholars consider chondrogenic chordoma to be the same lesion as mucinous chondrosarcoma. Treatment There are different clinical views on the treatment of chordoma, especially for chordomas occurring at the base of the skull, where the tumor is close to the brainstem and difficult to completely remove due to exposure difficulties, so it often recurs after surgery and the patient’s prognosis is poor. Since the tumor cells are not very sensitive to radiation, the effect of radiotherapy is also not satisfactory. Jacques et al. compared the 5-year survival of patients with chordoma who received different treatment regimens. 33% survived with surgery alone, 69% with radiotherapy alone, and 75% with surgery plus radiotherapy. From the statistical results, surgery combined with radiotherapy is an effective means to prolong survival. There is no consensus on the dose of radiation; some recommend a low dose of 30-40 Gy, while Cummings et al. recommend a high dose of 65-80 Gy, and most authors advocate 60-70 Gy. It is generally believed that chemotherapy drugs have no significant therapeutic effect on chordoma. The treatment of chordoma is primarily surgical, with radiation therapy as a supplement. Chordoma often extends to the nasopharynx, oropharynx, septal sinus, pterygoid sinus, pterygoid consternation, and subglottic fossa. Therefore, it is advisable for otorhinolaryngology and head and neck surgery to cooperate with neurosurgery to choose the best surgical approach, with the aid of nasal endoscopy, to remove the lesion as completely as possible and reduce complications Prognosis It is technically impossible to completely remove chordoma. Because: (1) the tumor is located at the base of skull, the site is deep and the structure is complicated, no matter what approach is adopted, it is difficult to achieve the ideal exposure and the field of view is limited; (2) the tumor is often closely connected with important nerves (such as optic, facial and vagus nerves), blood vessels (such as internal carotid and basilar arteries), brain and brain stem, which brings difficulties and risks to the operation. It is difficult and risky to do so. The tumor has no envelope, the tumor tissue is soft like jelly, the tumor is easy to remain or implant, and has a high recurrence rate of 85%, often eroding the paravertebral space, vertebral space, dura mater and spinal canal, etc., and is difficult to be completely removed.