Utility of Brachyury in Distinction of Chordoma from Cytomorphologic Mimics in Fine Needle Aspiration and Core Needle Biopsy
Vickie Y Jo, Jason L Hornick, Xiaohua Qian. Brigham and Women's Hospital & Harvard Medical School, Boston, MA
Background: Chordoma is a neoplasm of notochordal differentiation that most often occurs in the axial skeleton. Separation from mimics such as chondrosarcoma and metastatic mucinous adenocarcinoma (ACA) is therapeutically important but diagnostically challenging, especially in limited biopsies. Immunohistochemistry (IHC) for T or brachyury, a nuclear transcription factor expressed in chordoma, has recently proven diagnostically useful in whole-tissue sections. Our aim is to compare brachyury with conventional markers (S-100, EMA, keratin) in distinguishing chordoma from mimics in fine needle aspiration (FNA) and core needle biopsy (CNB) samples.
Design: In total, 20 chordoma cases (8 FNAs and 12 CNBs), 10 FNAs of chondrosarcoma, and 12 FNAs of metastatic mucinous ACA were evaluated. IHC was performed on cell blocks and CNBs using a rabbit polyclonal antibody to brachyury (Santa Cruz). Nuclear staining in at least 5% of tumor cells was recorded as a positive result. IHC (S-100, EMA, pan-keratin, AE1/AE3) performed at the time of diagnosis was also reviewed.
Results: Of the 20 chordoma cases, 15 were axial skeleton primary tumors and 5 were metastases (spine, pelvis, lung). Brachyury was positive in 17 (85%) chordoma cases; 14 had multifocal nuclear staining of moderate to strong intensity and 3 had weak focal staining. There were 5 sets of concurrent FNA and CNB; 4 pairs were brachyury-positive in both samples, and 1 pair was brachyury-positive in the CNB and negative in the cell block. S-100, EMA, and keratin stains were available for 13 cases: 9 (69%) cases (including the 3 brachyury-negative cases) were positive for S-100 and keratin or EMA, and 4 cases were keratin-positive but S-100-negative. No nuclear brachyury staining was seen in chondrosarcoma or metastatic mucinous ACA, though 2 ACA cases showed cytoplasmic staining.
Conclusions: Brachyury separates chordoma from cytomorphologic mimics with high sensitivity and specificity in limited biopsies. As a single test, brachyury has higher sensitivity (85%) than a combined panel of S-100 and epithelial markers (69%). When added to the conventional panel, brachyury increases sensitivity to 100% without sacrificing specificity. Cytoplasmic staining in mucinous ACA is a potential pitfall when interpreting brachyury in samples with scant cellularity.
Tuesday, March 20, 2012 11:15 AM
Platform Session: Section F, Tuesday Morning