Ependymal tumors with sarcomatous change ("ependymosarcoma"): a clinicopathologic and molecular cytogenetic study

Gliosarcomas are uncommon primary tumors of the central nervous system defined as exhibiting both glial and sarcomatous components. Sarcomatous change occurring in ependymal tumors is rare. We identified 11 such examples. There were 6 female and 5 male patients (median age, 18 y; range, 2 to 63). The tumors were located in the parieto-occipital (n=2), temporal (n=1), parietal (n=1), frontal (n=1), and occipital lobes (n=1), as well as the lateral ventricles (n=2), insula (n=1), cerebellopontine angle (n=1), and fourth ventricle/cerebellopontine angle (n=1). At presentation, the sarcomatous component was noted in 6 (of 10) cases and the ependymal element was grade III in 7 and grade II in 3 tumors, respectively. The sarcomatous component consisted of a reticulin rich, glial fibrillary acidic protein-negative fibrosarcoma (n=5) or pleomorphic spindle cell sarcoma (n=3), and 2 examples with heterologous elements: osseous and cartilaginous (n=1) and osseous only (n=1). The single case involving the fourth ventricle/left cerebellopontine angle consisted of subependymoma and fibrosarcoma components in roughly equal proportions at presentation. Fluorescence in situ hybridization studies performed with probes targeting the NF2 gene and other members of the protein 4.1 gene family demonstrated similar alterations in the ependymal and sarcomatous components in the cases tested, including polysomies/polyploidy (n=3), gains of 1q (n=3), deletions of 22q (n=2) and 6q (n=1), and monosomy 18 (n=1). There was no evidence of MDM2 or CCND1 amplification in any of the cases tested. On follow-up, 5 patients expired 4 months to 18 years after initial resection and 4 to 11 months after development of the sarcomatous component (mean, 7.6 mo); 1 patient is alive at 5 years with recurrent disease, and 1 is alive without recurrence 12 years after initial gross total resection followed by radiation therapy. Although rare, ependymal neoplasms must be included among the gliomas prone to undergo sarcomatous change and we propose the term "ependymosarcoma" for these tumors.