April 2022 – Bone and Soft Tissue & Cytopathology

Conventional chordoma.

Fine needle aspiration of the sacral mass demonstrates cellular smears with loosely cohesive groups and singly scattered epithelioid cells. These cells have a low nuclear to cytoplasmic ratio, abundant pale cytoplasm with vacuolations, mild nuclear size variation, conspicuous nucleoli. Binucleation and occasional large hyperchromatic cells were noted. Background showed mucinous/myxoid stromal material. Corresponding histological sections show nests and cords of polygonal cells with bland nuclei, pale eosinophilic cytoplasm with frequent cytoplasmic vacuolization (so-called physaliferous cells) infiltrating bone trabeculae. This morphology, in correlation with the strong positivity for pankeratin and brachyury and the imaging findings of a destructive sacral mass is characteristic of conventional chordoma.

There are several important differential diagnosis which should be excluded on the basis of morphology and immunophenotype. The groups of epithelioid cells with intracytoplasmic vacuolations and background myxoid stroma can mimic metastatic adenocarcinoma. In addition, the cells are positive for cytokeratins. However, brachyury positivity and radiological correlation will help in this distinction. The cytology, myxoid matrix and focal S100 positivity brings chondrosarcoma in the differential diagnosis. However, chondrosarcoma lacks cytokeratin and brachyury immunoreactivity and harbor IDH1/IDH2 mutations. In addition, imaging would show chondroid matrix in the mass lesion.

Lastly ecchordosis physaliphora (EP), represents a variant of a benign notochordal tumor that arises from the embryonic notochordal remnants. These lesions are usually small (less than 3 cm), and are incidental findings. These lesions are more common in clivus. Morphologically, they can look similar and will be brachyury positive. Therefore, distinction requires clinical and radiographic correlation.

Conventional chordoma is a malignant lytic, destructive lesion which arises in the bones of the axial skeleton (94 %), with a distribution of 32% at the skull-base, 32.8% in the mobile spine and 29.2% in the sacrum and coccyx. Extra-axial chordomas account for 6% of cases, occurring in other bones and soft tissue sites. Chordoma most commonly occur in the fifth to seventh decade of life. In the pediatric age group, speno- occipital region and cervical spine are commonly involved. As discussed above imaging findings show a lytic lesion with cortical destruction and a large soft tissue mass. The histological findings are characteristic of an infiltrating neoplasm with lobules of neoplastic cells separated by fibrous septi. The neoplastic cells are arranged in cords and nests in a pale myxoid background. The neoplastic cells have round nuclei with central nucleoli and eosinophilic to clear cytoplasm with prominent intracytoplasmic vacuolization (physaliphorous cells). By Immunohistochemistry, the neoplastic cells are diffusely positive for cytokeratin and variable positivity for S100. This malignant tumor recapitulates a notochordal phenotype of which it originates and has a hallmark expression of brachyury (encoded by TBXT gene), which shows nuclear immunoreactivity by IHC, as seen in this case. Recurrent mutations involving CDKN2A, LYST and TBXT (encodes brachyury) and mutations in epigenetic regulators and PI3K signaling such as PTEN have been identified. IDH1/IDH2 mutations are not present. The conventional chordomas are chemo resistant and are treated with wide surgical resection, with or without radiation therapy.

References

1. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973-1995. Cancer Causes Control. 2001 Jan;12(1):1-11.
2. Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006 Jun;209(2):157-65.
3. WHO Classification of Tumors Editorial Board. Soft tissue and bone tumors. Lyon (France): International Agency for Research on Cancer; 2020. ( WHO classification of tumors series, 5^th ed.; vol. 3).