HISTOPATHOLOGY, CLASSIFICATION, AND GRADING OF GLIOMAS

Neoplastic transformation occurs in all glial cell types of the human nervous system, producing a wide variety of clinico-pathological entit ies and morphological variants. Astrocytomas are most common and span an unusually wide spectrum, ranging from the slowly growing juvenile p ilocytic astrocytoma to the highly malignant glioblastoma multiforme. Diffusely infiltrating astrocytomas of the cerebral hemispheres show a n inherent tendency for progression towards a more malignant phenotype . This change is morphologically categorized in histologic grading sch emes (e.g., WHO Grade II to TV) and is associated with the sequential acquisition of genetic alterations, including mutations in the p53 and homozygous deletions of the p16 tumor suppressor genes. Loss of heter ozygosity on chromosomes 10 and 19q as well as amplification of the EG F receptor are largely restricted to malignant gliomas and thus consid ered late events in astrocytoma progression. Gliomas often show phenot ypic expression of different glial cell lineages (e.g., oligoastrocyto ma). Recent studies suggest that the occurrence of mixed gliomas is no t indicative of a polyclonal origin but rather reflects altered gene e xpression, leading to a change in the balance of growth factors influe ncing glioma differentiation. (C) 1995 Wiley-Liss, Inc.