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.