[GLIOBLASTOMA]. Glioblastoma is a WHO grade IV glial neoplasm of neuraxis and one of the highly aggressive malignancies causing death in most patients in <1 year. Glioblastoma is also undoubtedly the most polymorphic of any know neoplasm and is the reason for its previous characterization as “Glioblastoma multiforme” suggesting multiple forms. Two morphologic features are essential for the diagnosis: necrosis and endothelial proliferation. The tumor shows serpiginous necrosis with palisading around necrotic foci.
[GLIOBLASTOMA]. An area of necrosis is shown with tumor cell palisading. Note the pink cellular necrosis in the center (big arrow). Necrosis can be seen either in tumors or in adjacent normal brain in patients who have received radiation for various neoplasms. Thus a history of prior radiation to the brain must be entertained when necrosis is seen in a brain tumor biopsy.
[GLIOBLASTOMA]. Large areas of necrosis in glioblastoma are seen as ring-enhancing lesions in brain CT scans. Stereotactic biopsies of such tumors may yield necrotic foci with or without viable tumor cells. In the absence of viable glial tumor cells a firm diagnosis of glioblastoma cannot be made. However, a high-grade glial neoplasm (arrow) with abundant tumor necrosis (arrowhead) is nothing but a glioblastoma.
[GLIOBLASTOMA]. Vascular proliferation is another essential finding in glioblastoma and can take one of two forms or both. The more common glomeruloid vascular proliferation of endothelial cells also contains proliferating smooth muscle cells and is also commonly seen in low-grade gliomas such as pilocytic astrocytoma. The less common intravascular endothelial cell proliferation is a rather specific to high-grade glial tumors and characterized by reduction in lumen diameter by proliferating endothelial cells.
[GLIOBLASTOMA]. Note glomeruloid vascular proliferation with plump large cells.
[GLIOBLASTOMA]. The tumor is usually hypercellular and composed of variety of cell types including small cells with hyperchromatic nuclei and frequent mitoses (arrow) similar to small cell neuroendocrine carcinoma. However, the tumor cells in glioblastoma show pink glial-quality cytoplasm and may show evidence of a preexisting lower grade glial neoplasm. Grade 2 or grade 3 glial neoplasms may progress to glioblastoma but may retain some of its lower grade features if ample sampling of tumor is performed.
[GLIOBLASTOMA]. This tumor shows an area composed of gemistocytic cells suggestive of evolution from gemistocytic astrocytoma. However, microgemistocytes can also be seen in an otherwise de novo glioblastoma with no other evidence of a prior glial neoplasm.
[GLIOBLASTOMA]. The cells in some glioblastoma can have “epitheliod” or “rhabdoid” morphology with abundant pink cytoplasm pushing the nucleus to the side (arrowhead). These cells should not be confused with gemistocytes which are smaller and have an obvious glial look. A tumor composed purely of these cells must be distinguished from metastatic carcinoma, melanoma, and rhabdoid tumors. However, glioblastoma are almost always composed of more than one cell type, a feature of diagnostic importance.
[GLIOBLASTOMA]. The tumor cells in this example look like large cell lymphoma or a poorly differentiated carcinoma. However, the presence of pink fibrillary cytoplasm of glial-quality suggests the correct diagnosis.
[GLIOBLASTOMA]. Laminated calcium spherules also known psamomma bodies can also be seen in an otherwise de novo glioblastoma and do not necessarily indicate either a coexisting or prior oligodendroglioma. The cells in grade II oligodendroglioma have round uniform nuclei as opposed to oval and irregular nuclei seen in glioblastoma.
[GLIOBLASTOMA]. Vimentin positivity is a constant finding in glioblastoma but may also be seen in metastatic melanoma, sarcomas, some carcinomas, and lymphomas. However, a tumor negative for vimentin is a suspect glioblastoma.
[GLIOBLASTOMA]. Immunohistochemical staining for glial fibrillary acidic protein (GFAP) is a diagnostic feature of glial origin in appropriate context with few exceptions. Focal or diffuse positivity for GFAP is the rule in glioblastomas.
[GLIOBLASTOMA]. Note a very high Ki67 proliferation index with about 50% of the tumor cells showing nuclear staining.
[GLIOBLASTOMA]. The tumor cells show diffuse positivity for CD56.
[GLIOBLASTOMA]. Tumor cells can often show positive staining for various cytokeratins including AE1:AE3, Cam 5.2 and CK-7. The staining is usually focally seen and may confuse unwary pathologists of this phenomenon. Cytokeratin alone cannot be used to distinguish glioblastoma from a metastatic carcinoma.
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