Conventional Chordoma

Staging is according to bone sarcoma protocols (see TNM staging of tumors of bone).

The hallmark of chordoma is the expression of brachyury (encoded by TBXT). In 27% of cases, this is associated with copy-number gain of TBXT, a transcription factor required for notochordal development. This recapitulates the tandem duplication of TBXT that underlies familial chordoma. The strong association of rs2305089 in TBXT in patients with chordoma suggests this SNP contributes substantially to the development of chordoma. Brachyury has also been shown to act as a master regulator of an elaborate oncogenic transcriptional network encompassing diverse signaling pathways, including components of the cell cycle and extracellular matrix. Growth arrest and senescence upon silencing of TBXT in chordoma cell lines add to the critical role of TBXT in chordoma. Additionally, PI3K signalling mutations have been reported in 16% of cases, and mutations (always inactivating) of LYST have been described in 10% of cases. Phosphorylated and total EGFR (HER1) appears to play an important role in the disease, as it is expressed in 47% and 67% of chordomas, respectively, and EGFR (HER1) inhibitors reduce cell survival.

Chordoma presents as a lobular solid mass with a gelatinous appearance, destroying bone and extending into surrounding soft tissue. Sacrococcygeal tumors tend to be larger than those at other sites, most likely related to a longer symptom-free period.

Conventional chordoma is composed of large epithelioid cells with clear to light eosinophilic cytoplasm, separated into lobules by fibrous septa. The tumor cells may have bubbly cytoplasm (physaliphorous cells). They are arranged as cords and nests embedded within an abundant extracellular myxoid matrix, or as more densely arranged epithelioid packets. Chordomas often show a substantial degree of intratumoral cytological heterogeneity, with features including nuclear atypia and pleomorphism ranging from minimal to severe. In the latter, mitotic figures can be easily detected, and large areas of tumor necrosis may be present. Chondroid chordoma refers to chordoma in which a large area of the matrix mimics hyaline cartilaginous tumors.

Immunohistochemistry
The tumor is diffusely immunoreactive for cytokeratin and EMA and shows variable S100 positivity.

Differential diagnosis
The diagnostic hallmark is the expression of brachyury, which helps to distinguish chordoma from chondrosarcoma, carcinoma, and chordoid meningioma. The differential diagnosis includes metastatic carcinoma, chondrosarcoma, chordoid meningioma, and myoepithelial tumor of bone.

Not clinically relevant.

The overall median survival time is 7 years. As many as 40% of chordomas arising at sites other than the base of the skull metastasize. Metastatic sites include lung, bone, lymph nodes, and subcutaneous tissue. It is unclear whether chondroid chordomas behave differently than conventional chordomas.

No diagnostic molecular markers have been reported.

Essential: bone tumor compatible with imaging; voluminous epithelioid cells exhibiting notochordal differentiation embedded in copious myxoid matrix; brachyury and cytokeratin expression.