The CSF is usually normal but an increase in CSF protein (more than 100 mg/dL in many cases), as well as a pleocytosis of 10 to 100 cells or more, mostly lymphocytes, may result from a tumor extending to the meningeal surface or the ventricular wall. Malignant cells, carried in the CSF, rarely may form distant foci on spinal roots or cause widespread meningeal gliomatosis. Extraneural metastases, involving bone and lymph nodes, are very rare; usually they occur only after a craniotomy has been performed. Approximately 50 percent of glioblastomas occupy more than one lobe of a hemisphere; between 3 and 6 percent show multicentric foci of growth and thereby simulate metastatic cancer. A legitimate question is whether these tumors can have a multicentric origin or become multifocal as a result of spread via CSF pathways. We have the impression that the first configuration does exist but is not common.
The imaging appearance is usually that of an inhomogeneous mass, often with a center that is hypointense and nonenhancing. An irregular rim of contrast enhancement surrounds the core lesion, and is surrounded by nonenhancing edematous brain tissue, consisting of a combination of infiltrating tumor cells and vasogenic edema (Fig. 30-2). It is not uncommon to see small nodular contrast enhancing lesions adjacent to, but distinct from, the primary lesion. Part of one lateral ventricle is often distorted, and both lateral and third ventricles may be displaced. Necrotic and sometimes cystic areas appear on imaging studies. An MRI series by Ulmer and colleagues showed that 70 percent of patients show evidence of a small region of restricted diffusion immediately surrounding the tumor in the postoperative period; it is likely that these regions may represent hypercellular tumor areas or ischemia that precedes necrosis.
The tumor has a variegated appearance, being a mottled gray, red, orange, or brown, depending on the degree of necrosis and presence of hemorrhage, recent or old. The characteristic histologic findings of glioblastoma are hypercellularity with pleomorphism of cells and nuclear atypia; identifiable astrocytes with fibrils in combination with primitive forms in many cases; tumor giant cells and cells in mitosis; hyperplasia of endothelial cells of small vessels; and necrosis, hemorrhage, and thrombosis of vessels. This variegated appearance distinguishes glioblastoma from the anaplastic astrocytomas, which show frequent mitoses and atypical cytogenic features but no grossly necrotic or hemorrhagic areas. The vasculature and fibroblasts can undergo a sarcomatous transformation giving the tumor a mixed appearance that is termed gliosarcoma. The histologic grade of glioblastoma may vary from site to site within a tumor and it is common for sites of low-grade astrocytoma and glioblastoma to coexist; in some high-grade tumors there are even sites of well-differentiated astrocytoma. This relates to a problem that arises in interpreting single small biopsy samples taken for diagnosis. It is a fair statement that the most aggressive component determines the tumor’s behavior.