The distinction between
chondrosarcoma and
chordoma of the skull base/head and neck is prognostically important; however, both have sufficient morphologic overlap to make delineation difficult. As a result of gene expression studies, additional candidate markers have been proposed to help in separating those entities. We sought to evaluate the performance of new markers:
brachyury, SOX-9, and podoplanin alongside the more traditional markers
glial fibrillary acid protein,
carcinoembryonic antigen, CD24, and
epithelial membrane antigen.
Paraffin blocks from 103 skull base/head and neck chondroid
tumors from 70 patients were retrieved (1969-2007). Diagnoses were made based on morphology and/or whole-section immunohistochemistry for
cytokeratin and
S100 protein yielding 79
chordomas (comprising 45 chondroid
chordomas and 34 conventional
chordomas), and 24
chondrosarcomas. A tissue microarray containing 0.6 mm cores of each
tumor in triplicate was constructed using a manual array (
MTA-1; Beecher Instruments). For visualization of staining, the ImmPRESS detection system (Vector Laboratories) with 2-diaminobenzidine substrate was used. Sensitivities and specificities were calculated for each marker. Core loss from the microarray ranged from 25 to 29% yielding 66-78 viable cases per
stain. The classic marker,
cytokeratin, still has the best performance characteristics. When combined with
brachyury, accuracy improves slightly (sensitivity and specificity for detection of
chordoma 98 and 100%, respectively). Positivity for both
epithelial membrane antigen and AE1/AE3 had a sensitivity of 90% and a specificity of 100% for detecting
chordoma in this study. SOX-9 is apparently common to both notochordal and cartilaginous differentiation, and is not useful in the
chordoma-
chondrosarcoma differential diagnosis.
Glial fibrillary acid protein,
carcinoembryonic antigen, CD24, and
epithelial membrane antigen did not outperform other markers, and are less useful in the diagnosis of
chordoma vs
chondrosarcoma. Podoplanin still remains the only positive marker for
chondrosarcoma, though its accuracy is less than previously reported.