Poorly Differentiated Chordoma

Staging is according to bone sarcoma protocols.

In most cases, cytogenetic studies have identified deletions involving SMARCB1; these may be heterozygous or homozygous and of variable size, and they can be detected by DNA sequencing. There is no evidence to date of single-nucleotide variants accounting for loss of SMARCB1 protein. A subset of cases also shows heterozygous co-deletion of the EWSR1 locus, which lies in close proximity to SMARCB1. A minority of cases appear to have intact SMARCB1 and loss of SMARCB1 expression, but the mechanism by which this is brought about is presently unclear. Unsupervised clustering analysis of DNA promoter methylation profiles indicates that the presence of SMARCB1 deletions in these tumors readily distinguishes them from conventional chordoma, as well as the atypical teratoid/rhabdoid tumor.

The size of tumors generally ranges from 2.0 cm to >10 cm, although most are about 5.0 cm at presentation. Descriptions of the cut surface are, to date, lacking; poorly differentiated chordomas are destructive and may be well demarcated and multilobulated.

Poorly differentiated chordoma is composed of cohesive sheets or nests of epithelioid cells, often with a focal rhabdoid morphology. There is relatively abundant eosinophilic cytoplasm and scattered cytoplasmic vacuoles reminiscent of signet-ring cells. The nuclei are round to ovoid, with vesicular chromatin, and they reveal mild to moderate pleomorphism; mitotic activity is increased. The physaliphorous cells typical of chordoma with classic features are absent. Similarly, extracellular myxoid stroma, if present, is generally no more than focal. Geographical necrosis is often conspicuous.

Immunohistochemistry
The tumors are immunoreactive for cytokeratin and brachyury (encoded by TBXT), with variable positivity for S100. A diagnostic feature is the loss of SMARCB1 (INI1) expression.

Differential diagnosis
The differential diagnosis includes malignant rhabdoid tumor and rhabdoid meningioma.

Not clinically relevant

Treatment consists of a combination of surgery, radiation therapy, and chemotherapy. Fewer than 60 cases have been reported in the literature, but this subtype of chordoma is associated with a poor prognosis – worse than that of conventional chordoma.

FISH can be used to identify deletions in SMARCB1, and these may be associated with a co-deletion of the EWSR1 locus. FISH for EWSR1 in such tumors may exhibit a complex pattern that is generally unlike the typical EWSR1 rearrangements and must be interpreted with caution.

Essential: bone tumor with compatible imaging; poorly differentiated malignant neoplasm arising in the axial skeleton; positive immunohistochemical staining for keratin and brachyury; loss of SMARCB1 (INI1) expression.