Utility of brachyury in distinction of chordoma from cytomorphologic mimics in fine‐needle aspiration and core needle biopsy

Abstract

Chordoma is a neoplasm of notochordal differentiation that typically occurs in the axial skeleton. Accurate diagnosis is therapeutically important but can be challenging, especially in fine-needle aspiration (FNA) and core needle biopsy (CNB). Immunohistochemistry for the transcription factor brachyury (T) has recently proven diagnostically useful in whole-tissue sections. Our aim was to compare brachyury performance with conventional markers (S-100, EMA, keratin) and to evaluate its utility in distinguishing chordoma from cytomorphologic mimics. Brachyury immunohistochemistry was performed on chordoma (8 FNA, 12 CNB), chondrosarcoma (10 FNA), and metastatic mucinous adenocarcinoma (12 FNA). Immunohistochemistry performed at the time of diagnosis was also reviewed. Brachyury was positive in 17 (85%) cases of chordoma and typically showed moderate-to-strong nuclear staining. Of five sets of concurrent FNA and CNB, four pairs were positive for brachyury in both samples and one pair was positive for brachyury in the CNB and negative in the cell block. S-100, EMA, and keratin stains were available for 13 chordomas: 9 (69%) cases (including the 3 negative for brachyury) were positive for S-100 and keratin or EMA; 4 cases were keratin positive but S-100 negative. No nuclear brachyury staining was seen in chondrosarcoma or adenocarcinoma, though two adenocarcinomas showed cytoplasmic staining. Brachyury separates chordoma from cytomorphologic mimics with high sensitivity and specificity in small biopsies. As a single test, brachyury has higher sensitivity than a combined panel of S-100 and epithelial markers. When added to the conventional panel, brachyury increases sensitivity to 100% without sacrificing specificity.

Chordomas at High Prevalence in the Captive Population of the Endangered Perdido Key Beach Mouse (Peromyscus polionotus trissyllepsis)

“…Recent research, however, has shown the transcription factor brachyury to be a highly specific and reliably sensitive marker for identification of chordoma in humans, particularly when used in conjunction with cytokeratin. 19,20,38 In the current study, the neoplasms in PKB mice and the positive-control ferret chordoma exhibited strong nuclear immunoreactivity for brachyury and cytoplasmic immunoreactivity for cytokeratin, supporting the diagnosis of chordoma and suggesting that brachyury is a viable marker for chordomas in PKB mice. It was not clear why decalcified primary masses exhibited cytoplasmic immunoreactivity to brachyury.…”

FNA biopsy of secondary nonlymphomatous malignancies in salivary glands: A multi‐institutional study of 184 cases

“…Our case of secondary chordoma demonstrated epithelioid cells with vacuolated cytoplasm and round nuclei with small nucleoli amid a background of chondromyxoid extracellular matrix. Our diagnosis of this secondary chordoma is based on the patient's known history of a clival chordomas, 3.5 years before salivary gland involvement, and positive immunohistochemical staining for brachyury and SOX9 of the tumor cells …”

“…Our diagnosis of this secondary chordoma is based on the patient's known history of a clival chordomas, 3.5 years before salivary gland involvement, and positive immunohistochemical staining for brachyury and SOX9 of the tumor cells. 45,46…”

Recent advances in understanding and managing chordomas

“…The Brachyury gene is also implicated in various human carcinomas and could be responsible for the epithelial-mesenchymal transition allowing tumors to metastasize 22– 25 . In addition, the uniquely high levels of expression of the Brachyury protein in chordomas have allowed scientists and labs to differentiate them from other tumors of the neuroaxis, such as chondrosarcomas, with relatively high sensitivity and specificity 26– 31 . The degree of Brachyury expression, however, has not shown a prognostic indication in chordomas 32 .…”