DefinitionPrimary, malignant bone neoplasm showing notochordal differentiation; it comprises conventional, poorly differentiated and dedifferentiated types.ICD-O Codes9372/3 Conventional chordoma9370/3 Poorly differentiated chordoma9372/3 Dedifferentiated chordomaICD-11 Codes2B5K & XH9GH0 unspecified malignant soft tissue tumours or sarcomas of bone or articular cartilage of other or unspecified sites & Chordoma NOS2B5K & XH17D8 unspecified malignant soft tissue tumours or sarcomas of bone or articular cartilage of other or unspecified sites & Chondroid chordoma2B5Z & XH7303 malignant mesenchymal neoplasm of unspecified type & Dedifferentiated chordomaRelated TermsNoneSubtypesConventional; Chondroid; Dedifferentiated; Poorly differentiatedLocationSkull base chordomas typically arise from the clivus. Parasellar or extending upwards towards the sella is common. Complete intrasellar involvement is rare. Co-existence of chordoma and pituitary PitNET / adenoma is exceptional.Clinical FeaturesIntrasellar chordomas present with cranial nerve dysfunction (88.1%), visual disturbances and endocrine abnormalities (52.8%), including hyperprolactinemia and/or pituitary insufficiency. Headaches are rare.Imaging: Chordomas appear as destructive midline lesions. On MRI, T1 sequences are typically low signal (lower than clivus fat), T2 sequences are high signal with variable enhancement.EpidemiologyIncidence is 0.088/1,000,000 individuals, accounting for 0.5% of primary central nervous system tumors. Chordomas account for 0.5% of sellar region lesions. The skull base is the primary site in approximately 38% of patients. Both children and adults are affected. Adults with intrasellar chordomas are older than those with non-intrasellar skull base chordomas (mean: 55.5 years vs 43.3 years). There is a higher incidence in females (sex ratio 1.16).EtiologyMost chordomas are sporadic. Familial cases have been reported with germline TBXT gene duplication. Associated with tuberous sclerosis.PathologyChordomas likely derive from notochordal remnants that persist after development in a subset of individuals. The molecular mechanisms of notochordal remnant transformation are unclear. Germline TBXT gene duplication (27% of cases) and PIK3CA signaling mutations (16%) have been described. A novel LYST inactivating mutation (10%) has also been reported. In skull base chordomas, alterations in SWI/SNF complex members PBRM1/SETD2 and homozygous deletion of CDKN2A (16%) are the most common events. Loss of INI1 expression due to homozygous SMARCB1 gene deletion occurs in poorly differentiated chordomas.Gross AppearanceChordomas present as lobulated solid tumors with a gelatinous appearance typically invading the bone and extending into the surrounding tissue.HistopathologyConventional chordomas show lobular architecture, with lobules separated by fibrous septa. Tumor cells form trabecular or cord-like structures in a myxoid stroma. Cells are large, with clear cytoplasm and eosinophilic. When the cytoplasm is vacuolated or bubbly, they are defined as physaliphorous cells. Multinucleation and nuclear inclusions can be observed. Nucleoli are prominent, with rare mitotic figures and apoptotic bodies.Subtypes: Chondroid chordoma mainly consists of hyaline cartilage-like extracellular matrix.Dedifferentiated chordoma is a biphasic tumor, composed of conventional chordoma juxtaposed to high-grade sarcoma. In the conventional component, Brachyury and cytokeratin expression is preserved while sarcomatous areas can lose them.Poorly differentiated chordoma consists of epithelioid or rhabdoid cells, lacking myxoid areas and physaliphorous cells. Retained Brachyury expression is noted. Loss of INI1 expression.Immunohistochemistry: Brachyury expression serves as a diagnostic marker.Differential Diagnosis: Includes benign and atypical chordomas. Chondroid chordomas should be distinguished from low-grade chondrosarcomas.Cyto-pathologySquash or imprint preparations show clusters or dispersed uniform cells in myxoid and/or fibrillary matrix, with weakly eosinophilic or clear, vacuolated cytoplasm (physaliphorous cells).Molecular Pathology DiagnosisNo diagnostic molecular markers for conventional chordoma have been reported. Homozygous SMARCB1 deletion supports the diagnosis of poorly differentiated chordoma.Essential and Desirable Diagnostic CriteriaEssential CriteriaConventional chordoma: epithelioid and physaliphorous cells in a myxoid to chondroid matrix and Brachyury expression.Dedifferentiated chordoma: additional sarcomatous component.Poorly differentiated chordoma: aggregates of atypical epithelioid to rhabdoid cells; loss of INI1 expression and retained Brachyury.StagingChordomas are staged according to the bone sarcoma protocols.Prognosis and Predictive FactorsChordomas are slow-growing but locally aggressive tumors. Incomplete resection is the main factor affecting prognosis. Patients with intrasellar chordomas have a worse prognosis than those with skull base chordomas, possibly due to incomplete resection and postoperative endocrine sequelae. Dedifferentiated and poorly differentiated chordomas are highly aggressive tumors.
