It is important to remark that CNS tumors do not currently have TNM designations [4]. Attempts at developing a TNM-based classification and staging system for CNS tumors have been disappointing. There are multiple reasons for this. (1) Tumor size is significantly less relevant than tumor histology and tumor grading (Table 9.2). Thus, the location of the tumor, so the T classification, is less pertinent than the biologic nature of the tumor itself. (2) Since the brain and spinal cord have no lymphatics, the N classification does not apply. (3) An M classification is not pertinent to the majority of CNS tumors, because they have tendency to recur locally rather than disseminating at distance.

Neuroepithelial tissue tumors are by far the most common form of brain tumors. They are commonly referred to as gliomas. There are three types of gliomas, namely astrocytomas, oligodendrogliomas, and ependymomas. Gliomas are by far the most common and more ominous brain tumor type. Tumors deriving from the meninges, i.e., meningiomas, are another common form of CNS tumors. Less frequent ­histotypes include embryonal tumors, pineal gland tumors, choroids plexus tumors, ependymal tumors, and tumors of the cranial and paraspinal nerves.

On the basis of histological features, CNS tumors are divided into low-grade and high-grade tumors. Grading is based on the degree of nuclear atypia, mitosis, microvascular proliferation, and necrosis. Grading is clinically important because prognosis worsens as tumor grading increases. Tumor grade is determined by multiple histological sampling of tumor tissue. Low-grade gliomas are grade I and II, while high-grade gliomas are grade III and IV. Since histological features may vary within different areas of the same tumors, the most malignant region determines the grade of the tumor. Oligodendrogliomas, ependymomas, and astrocytomas can be either grade II or grade III, depending on the histological features. Grade III astrocytomas are commonly referred to as anaplastic astrocytomas. Glioblastoma, a grade IV glioma, is the most malignant as well as the most common form of gliomas, accounting for about 50% of all gliomas [5]. Glioblastomas are exceptionally aggressive tumors that are generally resistant to treatment. Average survival is less than 1 year from diagnosis. Glioblastomas are characterized by hypercellular anaplastic glioma cells with marked mitotic activity as well as necrosis and endothelial proliferation. Neoplastic cells frequently reveal pleomorphism showing different histological features such as small homogeneous cells with scant cytoplasm, fibrillary-shaped cells, multinucleated giant cells, and cells with pleomorphic nuclei and cytoplasm [6]. Because of such cellular pleomorphism, the tumor is often referred to as glioblastoma multiforme (GBM) [6]. Histological features in glioblastomas are associated with specific genetic alterations and with clinical outcome: the presence of necrosis is associated with poor survival, while the presence of oligodendroglial components is predictive of longer survival [7]. Amplification of the epithelial growth factor receptor (EGFR) is associated with necrosis and worse outcome [6].

Recurrence of disease is frequent in brain tumors. Recurrent gliomas are termed secondary gliomas. Clinical observations and biological studies differentiate primary and secondary gliomas. Primary gliomas develop without clinical or histological evidence of a less malignant precursor lesion. They represent the majority of cases (>90%) and they affect mainly elderly patients. Primary gliomas are genetically well characterized. The most common genetic alteration is PTEN (phosphatases and tensin homology) gene, which encodes a central domain that is important in the function of phosphatases. Secondary glioblastomas develop through progression from a low-grade diffuse astrocytoma to anaplastic astrocytoma and present in younger patients. Evolution of a recurrent high-grade glioblastoma is more rapid than a primary high-grade glioblastoma. In the ­pathway to secondary high-grade glioblastoma, TP53 ­mutations are the most frequent and earliest detectable genetic ­alteration, already present in 60% of precursor ­low-grade astrocytomas [8].