Pathology Considerations

Gliomas are classified into tumors of astrocytic, oligoden-droglial, ependymal, and mixed lineage. Diffuse astrocytic tumors are divided into three different grades by the World Health Organization (WHO) system:2 grade 2 (or astrocytomas [A]), grade 3 (or anaplastic astrocytomas [AA]), and grade 4 (or glioblastoma multiforme [GBM]). These tumors occur predominantly in adults. Diffuse astrocytic tumors can be subclassified into several histological types, including fibrillary, gemistocytic, small cell, and giant cell subtypes. Several of these histological types can be found within a single diffuse astrocytic tumor. Pilocytic astrocy-tomas are nondiffuse and localized. These tumors are often grade 1 and predominantly occur in children and young adults. GBM can be subclassified into two groups based on the duration of symptoms.3 Primary GBM presents de novo with a short duration of symptoms (often less than 3 months). Secondary GBM presents with a longer duration of symptoms or with a preceding grade 2 or 3 glioma.

Primary and secondary GBM usually present in patients greater than 60 and less than 40 years of age, respectively.

Oligodendrogliomas are divided into two grades: grade 2 (oligodendroglioma) and grade 3 (anaplastic oligodendroglioma). Some neuropathologists have described a grade 4 oligodendroglioma.4 Ependymomas are also classified as low and high grade.

One of the problems with the neuropathologic diagnosis of gliomas is their histologic heterogeneity. AA exhibits increased cellularity, nuclear atypia, and mitotic activity. Endothelial proliferation and necrosis are additional features of GBM. Depending on the extent of surgical sampling, some of the histologic elements that distinguish AA and GBM may not be present in the specimen submitted for pathological diagnosis, and some gliomas may be undergraded. Thus, molecular markers that assist in tumor grading are clinically useful.

In addition to histologic heterogeneity, diffuse gliomas often exhibit cell type heterogeneity. Both astrocytic and oligodendroglial elements are present in most diffuse gliomas, especially those of grades 2 and 3. When both of these elements comprise a significant proportion of the tumor, the glioma may be classified as a mixed oligoastro-cytoma (MOA). However, the assessment of the appropriate proportions is subjective, with a continuum from "pure" astrocytomas, through mixed astrocytomas, to "pure" oligodendrogliomas. In a comparison of corresponding grade tumors, patients with oligodendrogliomas have a better survival than patients with astrocytic tumors (the survival of patients with MOA is intermediate). Thus, molecular tools that assist with morphological classification are clinically useful.

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