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.

Keywords: brachyury; chordoma; fine-needle aspiration; immunohistochemistry.