Genetics and Molecular Biology of Intramedullary Spinal Cord Tumors John H. Chi, MD, MPH * , Kristine Cachola, BA, Andrew T. Parsa, MD, PhD Department of Neurological Surgery, University of California, San Francisco, M779, PO Box 0112, 505 Parnassus Avenue, San Francisco, CA 94143, USA Intramedullary spinal cord tumors (IMSCTs) comprise 5% to 6%% of all central nervous system (CNS) tumors. Among intradural spinal tumors, intramedullary neoplasms account for only 8% to 10%, whereas extramedullary tumors, such as schwannoma and meningioma, predomi- nate [1]. The most common intramedullary lesions are spinal ependymoma (60%) and spinal astrocy- toma (10%–20%), but others include hemangio- blastoma (3%–8%), cavernous malformation, metastases, and lipoma [1]. Although these tumor types exist in the brain, patients with spinal cord tumors tend to be younger and the spinal cord tu- mors do not seem to occur in connection with pri- mary brain tumors. Spinal astrocytoma seems to occur in childhood or young adulthood, whereas ependymoma can occur throughout life but most commonly in the early to middle adult years. Much less attention seems to be paid to spinal cord tumors because of their overall rarity. Certain genetic syndromes are associated with IMSCTs and provide a special opportunity to study their genetics and molecular biology. His- torically, ependymoma and astrocytoma of the spinal cord have been little distinguished from their cerebral counterparts. More and more evi- dence suggests that distinct differences in genetics and molecular biology exist between primary tu- mors in the brain and spinal cord with similar his- tology, however. Genetic mutations associated with spinal ependymoma Ependymomas are neuroectodermal tumors that occur in the brain and spinal cord. They are thought to arise from the ependymal lining of the ventricles and spinal canal. Most ependymomas are sporadic, but they are also associated with patients with neurofibromatosis. Intramedullary ependymoma is particularly amenable to surgical resection because of a defined tumor and cord interface, which is usually preserved and used to separate tumor from cord. A diagnosis of epen- dymoma on pathologic examination should prompt a full attempt at gross total resection without risking permanent spinal cord injury. Three general types exist and include myxopa- pillary (World Health Organization [WHO] grade I), benign ependymoma (WHO grade II), and anaplastic ependymoma (WHO grade III). Myx- opapillary ependymomas are a unique type of tumor because they are almost exclusively found at the conus and filum terminale and are therefore considered intradural extramedullary. Interest- ingly, myxopapillary ependymoma has been shown to exhibit a much higher propensity for aneuploidy or polyploidy, especially of chromosome 7, com- pared with other ependymomas based on chromo- genic in situ hybridization (CISH) [2,3]. This unique genetic trait may explain its unique localization within the spinal cord. Anaplastic This article is adapted, in part, from: Parsa AT, Chi JH, et al. Intramedullary spinal cord tumors: molecular insights and surgical innovations. Clinical Neurosurgery 2005;52:76–84; with permission. * Corresponding author. E-mail address: chijo@neurosurg.ucsf.edu (J.H. Chi). 1042-3680/06/$ - see front matter Ó 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.nec.2005.10.002 neurosurgery.theclinics.com Neurosurg Clin N Am 17 (2006) 1–5