Poorly Differentiated Smarcb1/Ini1-Negative Chordomas

Aims: To analyze the clinicopathological characteristics of poorly differentiated chordomas (PDCs) with SMARCB1/INT1 loss in children. Materials: Four cases of PDCs were included in the study. Methods: Immunohistochemistry was performed with respect to brachyury, Glut-1, keratin 18, keratin 19, INI1 vimentin, S-100, CK, EMA, GFAP, etc. Fluorescence in situ hybridization (FISH) was performed for SMARCB1/INI1 from 3 patients. Results: Histologically, contrary to typical histologic features for conventional chordomas, 4 tumors were composed of ovoid or atypical fusiform cells. Sporadic physaliphorous cells were evident. Tumor cells had large vacuoles in the cytoplasm that were even remarkable on the imprint cytology slide. By immunohistochemistry, each case revealed loss of SMARCB1/INI1 expression and nuclear expression of brachyury. Glut-1, keratin 18. keratin 19, CK, EMA, and vimentin were positive in these PDCs. Except for 1 patient who had not yet completed FISH, the other 3 cases demonstrated the loss of SMARCB1/ INI1 gene by fluorescence in situ hybridization. Conclusion: Poorly differentiated SMARCB1/INI1-negative chordoma is a unique subset of chordoma representing a clinically, histopathologically, and molecularly distinct entity with rapid progression and poor prognosis which should not be confused with conventional chordomas. Sporadic physaliphorous cells (tumor cells with large vacuoles in the cytoplasm) provided important diagnostic clues of PDCs. Combination use of characteristic markers of notochord cells (brachyury, Glut-1, keratin 18, and keratin 19) along with INI1 were effective diagnostic tools.