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Tumors II: Glial and Glioneuronal Tumors

Last updated on Monday, April 20 2009 by gliageek

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A. Neurons

1. As differentiated neurons do not normally divide, tumors derived from such cells (ganglion cell tumors) are rare, and when they occur are usually benign.

2. As the external granular cell neurons of the cerebellum are actively replicating and migrating well into post-natal life, tumors derived from these primitive neurons (medulloblastomas) are the most common childhood brain tumor. Their primitive phenotype gives rise to rapidly dividing poorly differentiated discohesive cells with a high propensity for leptomeningeal dissemination. These growth characteristics also, however, render the neoplastic cells highly susceptible to therapy.

B. Glia

1. Astrocytes are the main replicating cell type within the brain and therefore astrocytomas are the most common tumors of the CNS. Perhaps as a result of this, they are the only CNS tumor for which a grading system of malignancy has been well established. While the term “low-grade” is used to describe the least malignant of these tumors (WHO grade II), this should not be mistaken for benign (WHO grade I), as virtually all patients with these tumors eventually die from them (median survival = 5 years, though some survive for a decade or more). The most malignant form of astrocytic tumor (WHO Grade IV) has retained the somewhat antiquated appellation "glioblastoma multiforme" and is the most common primary CNS tumor of adults, with a median survival of about a year. It is characterized by rapid growth resulting in necrosis, as well as vascular endothelial proliferation, a rather specific stromal response related to production of PDGF-A by the neoplastic astrocytes.

Astrocytomas may occur anywhere within the central nervous system, but usually involve the cerebral white matter. With increasing age comes increased tumor grade, with glioblastomas predominating in the older adult population. Most astrocytomas occur sporadically, but they may be also seen in a variety of syndromes including neurofibromatosis, Li-Fraumeni, and Turcot syndromes. Glioblastomas may develop by progression from lower grade glial tumors or de novo. The former are referred to as secondary glioblastomas, tend to occur in slightly younger patients (average age = 45), and nearly always contain mutations in the p53 gene. Glioblastomas arising de novo are called primary glioblastoms, occur in slightly older individuals (mean age = 55), and nearly always have normal p53 genes but overexpress the epidermal growth factor receptor. As of this writing (June 2002), these molecular profiles have no definite prognostic or therapeutic relevance, but are being built into clinical trials for this terribly malignant and recalcitrant tumor.

While adult astrocytic tumors are distributed within the brain based on relative mass, childhood astrocytic tumors primarily involve the later developing posterior fossa, especially the cerebellum. Luckily, however, the Bergmann glia providing the scaffolding of granular neuron migration are biologically different from other astrocytes and give rise to pilocytic astrocytomas (WHO grade I), which are well circumscribed, benign, usually easily resected tumors with excellent long term survivals.

2.Oligodendrocytes and their precursors do not replicate very much and consequently comprise a relatively small proportion of CNS tumors (about 10-20% of glial neoplasms). While these tumors look a lot like astrocytomas (both share a common precursor cell), they tend to behave in a significantly more benign fashion (median survival = 10-15 years for grade II oligodendrogliomas), and are uniquely susceptible to chemotherapy if they demonstrate classic1p deletions. Unfortunately, there are no specific histopathologic or immunohistochemical markers for this tumor. All tumors suspected of belonging to this family should be evaluated for 1p deletions, as preliminary evidence suggests that this chromosomal abnormality may be the first to trump histology as a predictor of chemoresponsiveness and perhaps even survival.

3. Ependymal cells also don’t replicate much once brain development is completed, and therefore are predominantly tumors of the childhood posterior fossa.