Cerebral granular cell astrocytomas: a Mib-1, bcl-2, and telomerase study

Granular cell (GC) astrocytoma is an uncommon variant of glioma that shares the cytologic features and high cytoplasmic lysosomal content with granular cell tumors elsewhere in the body. While the histogenesis and behavior of these neoplasms was originally in dispute because most were reported as single cases, the accumulated literature on approximately three dozen such lesions has now verified their usual astrocytic lineage and poor prognosis. Although the GC cell is thought to represent a degenerative process, little is known in these tumors about cell cycle regulation, as measured by Mib-1 and bcl-2 immunolabeling, or expression of other biomarkers of malignancy, such as telomerase. In our study, GC astrocytomas were similar to gemistocytic astrocytomas in their bland histology, often prominent perivascular lymphocytic cuffing and low Mib-1 labeling indices. Like gemistocytes, GCs appear to represent senescent, non-cycling cells. Absence of significant bcl-2 immunolabeling in our three cases, however, suggests that unlike gemistocytes, GC astrocytes develop senescence by mechanisms other than bcl-2 mediated apoptosis suppression. In one case in which frozen tissue was available for assay, we noted relatively high quantitative telomerase expression. The level paralleled that seen in other glioblastomas. Demise for our three patients occurred 3-25 months post-biopsy. Like gemistocytes, the presence of non-proliferative GCs signifies severe abnormalities in cell cycle regulation and maybe hallmarks of tumors with poor prognosis.