OLIGODENDROGLIOMAS

Oligodendrocytes maintain myelin and hover obediently about large neurons in the cerebral cortex. They occur, therefore, in both gray matter and white matter but are much more numerous in the latter, where they are regimented along axis cylinders. Neoplasms derived from these cells are found principally in adults and primarily in the cerebral hemispheres, where the frontal lobes are greatly favoured. Only rarely does an oligodendroglioma appear in the cerebellum, brain stem, or spinal cord. Radiographic calcification is common. Seizures may be present for many years preoperatively.

At surgery, the lesions are infiltrating tumors and therefore can resemble the well-differentiated astrocytoma. Focally, however, the neoplasm is often extremely cellular, gray, and fleshy, so it can simulate an anaplastic neoplasm. Heavy calcification in a cerebral neoplasm in an adult should alert the surgeon and the pathologist to the possibility of this entity, particularly if the mineralization occurs in a sinuous "gyriform" pattern.

The oligodendroglioma has a number of distinctive histologic features that usually permit a ready and unequivocal diagnosis in permanent sections, although the neoplasm can be difficult to recognize in frozen tissues. The nuclei are monotonously round and uniform, and are packed into cellular sheets that abut rather abruptly on the adjacent brain. In zones of cortical infiltration, perineuronal satellitosis is often more pronounced than in astrocytomas. Calcification is common as freestanding laminated bodies (calcospherites) or mineralization of blood vessel walls. The presence of delicate angulated segments of capillaries that parenthesize focal areas of the parenchyma is an additional vascular change. Vascular cells commonly proliferate in the oligodendroglioma, although not usually in the marked glomeruloid formation as noted in glioblastoma. Such vascular cell proliferation may be present in even the well-differentiated lesion, where it does not necessarily have malignant connotations.

The most distinctive and diagnostic feature of the oligodendroglioma is an artefact due to its propensity for imbibing water during ischemia or autolysis. When this fluid distends the cytoplasm, the bloated cells contain lucent perinuclear halos resembling the whites of fried eggs about their yolks. As diagnostically helpful as it is aesthetically pleasing, this artefact is, unfortunately, not present in tissues that are fixed rapidly, particularly those used for frozen sections. The presence of this artefact constitutes the one, and probably the only, occasion when a pathologist is pleased that tissues are transported in the physiologic but autolysis-promoting warm saline to which neurosurgeons occasionally entrust excised tissue.

The classic oligodendroglioma is readily recognized in permanent section, although the absence of the characteristic halos in frozen sections may make recognition of this neoplasm difficult during surgery. Such a lesion may be interpreted as an astrocytoma or, because of its high cellularity, an anaplastic astrocytoma. The presence of sheets of high cellularity, monotonous nuclear roundness, calcium, and the typical vascular formations at this point are all suggestive features. If difficulty persists in permanent sections, the GFAP method can be extremely helpful, because oligodendroglia contain microtubules rather than glial filaments. In concept, the oligodendrocyte is therefore negative with this technique. Nevertheless, GFAP-positive cells are observed in many oligodendrogliomas. Four distinct types of such cells have been identified: (1) entrapped reactive astrocytes, (2) neoplastic fibrillary astrocytes (which, if present in significant numbers may warrant a diagnosis of mixed glioma), (3) cells with the appearance of miniature gemistocytes ("minigemistocytes"), and (4) "gliofibrillary oligodendrocytes," which resemble typical oligodendrocytes in all respects except for a thin rim of GFAP-positive cytoplasm surrounding the nucleus. Both the "minigemistocytes" and "gliofibrillary oligodendrocytes" have been considered transitional cell types expressing an intermediate phenotype between the oligodendrocyte and the astrocyte. A recent study suggests that there is no prognostic significance to the presence of either cell type in an otherwise typical oligodendroglioma. The presence of large, classic gemistocytic astrocytes, however, was a negative prognostic factor, as would be expected for a mixed oligoastrocytoma with an anaplastic astrocytic component.

The typical oligodendroglioma described above merges with a continuum of increasingly cellular and pleomorphic lesions. Several four-tiered systems have been used for grading oligodendrogliomas. A recent study suggests, however, that for prognostic purposes, the spectrum of oligodendrogliomas best stratifies into only two groups, low grade and high grade. The high-grade lesions are characterized by histologic features typically associated with a poor prognosis, including microvascular proliferation, foci of necrosis, and significant mitotic activity. A rare lesion may exhibit mixed features of both high-grade (anaplastic) oligodendroglioma and glioblastoma multiforme; such lesions are difficult to classify (malignant oligodendroglioma versus glioblastoma). The importance of distinguishing between high-grade oligodendroglioma and glioblastoma lies in the fact that even the most anaplastic oligodendrogliomas generally have a better prognosis than that of glioblastoma.