MACROSCOPIC APPEARANCES

Oligodendrogliomas have a variety of macroscopic appearances. Small diffuse examples may be difficult to locate in resection specimens. Distortion of the normal cortical gray and white matter interface and discoloration of tissue provide clues to their location (Fig. 36.1). Other neoplasms are more obvious, appearing as moderately well-circumscribed, gray masses. The propensity of superficial oligodendrogliomas to invade the subarachnoid space may produce a neoplasm that sits partially on the cortical surface of the cerebrum.

MICROSCOPIC APPEARANCES

Oligodendrogliomas are composed of uniform cells (Figs 36.2–36.5). These readily infiltrate gray matter, but tend to produce a more abrupt edge in white matter (Fig. 36.2). A lobular architecture is sometimes seen and microcysts can be prominent, particularly in myxoid tumors. Small foci of dystrophic calcification are usually found, often at the edge of the neoplasm or in infiltrated gray matter. A delicate vasculature consisting of branching capillaries runs through typical oligodendrogliomas.

Cytoplasm is rather sparse and not easily identifiable in some cells. Artefactual clearing of the cytoplasm is common in paraffin-embedded material, particularly when fixation is delayed, and gives a ‘fried-egg’ appearance to the cells (Fig. 36.3a). Nuclei are round and usually contain faintly speckled chromatin. A single small nucleolus may be present. Cells occasionally adopt a slightly elongated form, but nuclei retain their characteristic uniformity. Some cells, termed ‘minigemistocytes’, have eccentrically placed nuclei and eosinophilic cytoplasm that is strongly immunoreactive for GFAP (Fig. 36.3d). This overlap with an astrocytic morphophenotype is not on its own indicative of mixed glioma status, but should prompt a search for anaplastic features. Exceptionally, ‘signet-ring’ cells may be evident. Invasion of the subarachnoid space is common (Fig. 36.4). Immunohistochemistry with antibodies to GFAP generally reveals labeling of only a small proportion of cells (Fig. 36.5). Immunoreactivity for myelin-specific proteins is rare. Mitoses are sparse, except in neoplasms with other anaplastic characteristics such as cytologic pleomorphism, microvascular proliferation, and areas of necrosis (Fig. 36.8).

MACROSCOPIC APPEARANCES

Classic ependymomas grow as circumscribed soft gray masses that are generally related to the ventricular system. They are commonest in the posterior fossa, where they may fill the fourth ventricle and pass through its exit foramina (Fig. 36.9).

Myxopapillary ependymomas generally appear as well-defined, lozenge-shaped neoplasms among the cauda equina, which they can sometimes envelop (Fig. 36.10). This behavior can hinder a complete surgical removal. Sectioning reveals tissue with a mucoid texture. Spontaneous hemorrhage into these neoplasms is quite common.

Subependymomas are firm lobulated intraventricular masses and are found predominantly in the fourth ventricle (Fig. 36.11).

MICROSCOPIC APPEARANCES

Ependymomas are generally composed of sheets of uniform cells with indistinct cytoplasmic borders and round or oval nuclei (Fig. 36.12). They are not diffuse gliomas; infiltration of adjacent tissues is minimal, except in some anaplastic examples. The nuclear:cytoplasmic ratio varies; cell density may be high, but infrequent nodules of densely packed cells may be scattered throughout paucicellular areas (Fig. 36.12c). Cells in these nodules may show more nuclear pleomorphism than surrounding cells, and an increased mitotic count. Mitoses should be infrequent and microvascular proliferation absent in classic ependymomas. Foci of micronecrosis without nuclear palisading may be found in classic ependymomas.

Ependymomas label variably with antibodies to GFAP (Fig. 36.13). Focal immunoreactivity for epithelial membrane antigen is sometimes seen around canals. Ultrastructural examination reveals microvilli and cilia on the luminal surfaces, and zonulae adherentes.

The pseudorosette is a perivascular anuclear zone of fibrillary processes that taper towards the vessel (Fig. 36.14). Pseudorosettes are a frequent, though not entirely specific, finding in ependymomas. Ependymal (true) rosettes with a central lumen and a halo of neoplastic cells are more specific, but found less consistently (Fig. 36.14). Rosettes and gland-like canals are a manifestation of epithelial differentiation in ependymomas.

Cellular ependymomas contain cells with a high nuclear: cytoplasmic ratio (Fig. 36.15). Few pseudorosettes are present, and cellular ependymomas do not contain paucicellular areas. Differentiating this variant from an anaplastic ependymoma is difficult, and depends on the identification of an increased mitotic count and cytologic pleomorphism in the latter. Microvascular proliferation and abundant necrosis are also features of most anaplastic ependymomas.

Rarely, intraventricular ependymomas exhibit a papillary pattern, and choroid plexus papilloma (CPP) then enters the differential diagnosis (Fig. 36.16). Papillary ependymomas do not have a subepithelial basement membrane over a fibrovascular core like the CPP, while the CPP does not contain pseudorosettes with tapering GFAP-positive processes.

Clear cell ependymoma may be confused with an oligodendroglioma, but the presence of pseudorosettes should declare its identity (Fig. 36.17). Some ependymomas are composed largely of elongated cells with an astrocytic morphology and have been referred to as tanycytic ependymomas (Fig. 36.18).

Criteria for the diagnosis of anaplastic ependymoma are rather subjective. Necrosis and capillary endothelial proliferation may be widespread in anaplastic ependymomas (Fig. 36.19). The WHO classification emphasizes atypical cytologic features (i.e. nuclear pleomorphism), a high cell density, and plentiful mitoses in its diagnosis. It is important to note that no histologic feature of ependymomas correlates reliably with prognosis.

Myxopapillary ependymomas are characterized by abundant mucin, which envelops and separates clusters and fronds of tumor cells (Fig. 36.20). These tumors usually have monomorphic round nuclei, and may show either epithelioid or glial differentiation. Regions of glial differentiation contain cells with elongated fibrillary processes. Cells with an epithelioid morphophenotype usually form papillary structures with a vascular core. Evidence of previous hemorrhage may be found in the form of hemosiderin-laden macrophages. Intratumoral blood vessels tend to have thick hyalinized walls. Mitoses and foci of necrosis are rare.

Subependymomas are composed of cells with uniform, round or oval nuclei and generally scanty perinuclear cytoplasm. The cells are clustered in small, scattered groups and separated by broad bands of closely packed fibrillary processes. Occasional cells have more abundant, homogeneous, perinuclear cytoplasm. Microcysts are a common finding (Fig. 36.21). Mitoses are absent.

MACROSCOPIC AND MICROSCOPIC APPEARANCES