Brachyury Expression in Extra-axial Skeletal and Soft Tissue Chordomas: A Marker that Distinguishes Chordoma From Mixed Tumor/Myoepithelioma/Parachordoma in Soft Tissue

Abstract

Axial chordoma represents approximately 1% of malignant bone tumors. This tumor expresses cytokeratins, specifically cytokeratin 19, and commonly S100. More recently brachyury, a transcription factor important in mesodermal differentiation, including notochord development, has been detected by immunohistochemistry in axial chordomas and hemangioblastomas but not chondrosarcomas or other neoplasms. In this report, we describe 10 cases (6 men, 4 women: age 18 to 68 y; mean 44.6) of extra-axial tumors, 8 in bone and 2 in soft tissue, with morphologic and immunohistochemical features identical to those of axial chordoma. Imaging excluded metastases from axial chordoma. Three tumors occurred in the tibia, the others in the rib, metatarsal, ulna, femur, pubis: 2 intracortical, 6 intramedullary. Both soft tissue brachyury-positive tumors, one involving the thumb the other the wrist, were sited in the juxta-articular region. Seven of the tumors were widely excised and these patients are disease-free but of the 3 tumors that recurred, 1 was curetted, 1 was marginally excised, and 1 had a pathologic fracture on presentation. Metastases have not occurred in any of the patients. We also confirm the expression of brachyury in hemangioblastomas, and for the first time demonstrates its expression in spermatogonia and testicular germ cell tumors by immunohistochemistry. Brachyury was not detected in a wide range of tumors including carcinomas, lymphomas, and sarcomas. In conclusion, we describe the first series of extra-axial skeletal chordomas bringing the total number of such cases reported in the literature to 11, and present the first report of 2 soft tissue chordomas as defined by brachyury expression.

Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases

“…[5][6][7] Although the morphological overlap between chordoma and clear cell renal cell carcinoma is well known, we have also encountered cases in which the distinction from central nervous system germ cell tumors such as seminoma and yolk sac tumor was considered, especially in the evaluation of poorly differentiated (anaplastic) chordomas. Within the spectrum of genitourinary neoplasia, rare brachyury immunoreactivity has been reported in testicular germ cell tumors (2/14 cases; most unspecified as to subtype), including focally within non-neoplastic testis.…”

“…5,7 A study presented in abstract form has also reported focal brachyury staining in four out of six seminomas, 3 whereas a very recent study reported no staining in six additional testicular germ cell tumors (four seminomas and two mixed germ cell tumors). 7 The current study was undertaken because of the potential morphological overlap of chordoma with these genitourinary tumors, the emerging recognition of true primary peripheral chordomas in unusual sites, 5,8,12,13 and the lack of a large comprehensive series of cases examined for brachyury expression.…”

“…5,7 A study presented in abstract form has also reported focal brachyury staining in four out of six seminomas, 3 whereas a very recent study reported no staining in six additional testicular germ cell tumors (four seminomas and two mixed germ cell tumors). 7 The current study was undertaken because of the potential morphological overlap of chordoma with these genitourinary tumors, the emerging recognition of true primary peripheral chordomas in unusual sites, 5,8,12,13 and the lack of a large comprehensive series of cases examined for brachyury expression.In this study, brachyury expression was not identified in any of the 111 germ cell tumors or 30 non-germ cell tumor testicular tissues investigated, including a lack of staining in the surrounding non-neoplastic testis of 10 whole-section seminomas. Although this finding contrasts with other reports of brachyury immunoreactivity in germ cell tumors (both seminoma 3 and unspecified subtypes 5 ) and non-neoplastic testis (spermatogonia), 5,7 it should be noted that both studies describe and/or depict immunoreactivity that is very focal in nature.…”

“…Although expression of the novel antigen brachyury has come to be considered a defining diagnostic feature of chordoma, [1][2][3][4][5][6] few studies have thoroughly addressed specificity of the antibody. Chondrosarcoma, the most recognized differential diagnostic consideration for chordoma, has been thoroughly evaluated in previous studies and does not express brachyury.…”

“…Chondrosarcoma, the most recognized differential diagnostic consideration for chordoma, has been thoroughly evaluated in previous studies and does not express brachyury. 2,[5][6][7][8][9] However, within the spectrum of genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell carcinomas may also be close morphological mimics of chordoma, particularly on a small biopsy sample. Immunoreactivity with the brachyury antibody has been reported in a few germ cell tumors, either in cases without reported subtype 5 or in seminomas; 3 however, a full characterization of staining by tumor subtype has not been evaluated in a large series.…”