PILOCYTIC ASTROCYTOMAS

Pilocytic Astrocytomas of the Optic Nerve, Hypothalamus, and Cerebellum

The pilocytic astrocytomas occurring at these three anatomic locations share several characteristics, including a high incidence in childhood, a number of distinctive pathologic features, and a slow rate of growth. It is extremely important that these lesions be distinguished from the infiltrative and almost always unresectable fibrillary or "diffuse" astrocytic neoplasms. Unlike these latter tumors, the pilocytic neoplasms show little tendency toward malignant degeneration.

Optic Nerve Pilocytic Astrocytoma (Optic Nerve Glioma)

The optic nerve is a cylindrical extrusion of the central nervous system partially compartmentalized along its long axis by fibro­vascular septa. The proliferation of cells within the nerve enlarges these compartments and, as a consequence, the nerve itself. Additional expansion is produced by the cells' extension into the subarachnoid space, where they proliferate into a circumferential mass made firm by a secondary collagenous reaction. This is sometimes referred to as hyperplasia of the optic nerve sheath. At surgery, the well-developed lesion is therefore a fusiform swelling that, in cross section, contains a central or eccentrically placed hypertrophic nerve surrounded by a firmer and whiter corona of leptomeningeal neoplasm and collagen. The neoplasm may occur anywhere along the nerve, from the optic chiasm to the globe. Multicentricity is common in Type I neurofibromatosis.

Microscopically, the uniformity of the nuclei of the optic nerve glioma is commensurate with the lesion's leisurely growth. The cells are either elongated forms or stellate cells producing a spongy tissue rich in mucopolysaccharide. The latter substance often lends a gelatinous quality to the macroscopic lesion, particularly the centrally placed enlarged nerve. The elongated cells often contain Rosenthal fibers.

Although the neoplastic cells in the lesions are astrocytic in morphology, their cell of origin is unknown, because similar cells are not recognized components of the normal nerve. The normal fibrillary astrocytes of the optic nerve produce only rare neoplasms. These occur predominantly in adults and are similar in their invasiveness and aggressiveness to the fibrillary astrocytic neoplasms.

The treatment of optic nerve gliomas has been controversial because of the long post-treatment intervals required to compare different therapies. From the point of view of a pathologist, the lesion has the expansile and invasive qualities of a neoplasm, albeit one well differentiated and slowly growing.

Hypothalamic Pilocytic Astrocytoma

The hypothalamic pilocytic astrocytoma is a soft, lobular, gray­tan lesion that, because of its slow growth, can attain considerable size. Positioned in the walls of the third ventricle, it is sometimes cystic and calcified. Anteriorly, the lesion merges clinically and pathologically with the optic nerve glioma. The distinction between a large chiasmal glioma and a hypothalamic glioma may be arbitrary, depending only on the predominant position of the lesion. A neoplasm similar to the hypothalamic glioma occasionally occurs in the brain stem, especially in neurofibromatosis.

Microscopically, hypothalamic glioma is formed of bland cells in solid sheets and lobules and a curious juxtaposition of elongated cells in fascicles about attenuated areas of microcysts. The elongated cells are especially likely to contain a structure of considerable diagnostic importance, the Rosenthal fiber. This intracytoplasmic hyaline eosinophilic body stains bright red with Masson's stain and dense blue with phosphotungstic acid/hematoxylin (PTAH). Tinctorially, the Rosenthal fiber therefore is consistent with an aggregated mass of glial filaments. By electron microscopy, the body is a dense amorphous structure anchored to the cytoplasmic glial filaments that are abundant in such cells. The body is negative, or only weakly positive, for GFAP. The Rosenthal fiber is an extremely helpful histologic feature, although it is not a diagnostic one, because it can occur also in periventricular gliosis-that secondary to craniopharyngioma being a notable and germane example. Vascular proliferation is sometimes noted in hypothalamic glioma, but it lacks the malignant connotation it has in fibrillary astrocytic neoplasms of the cerebral hemispheres, brain stem, or spinal cord.

The hypothalamic glioma of the juvenile type is histologically benign, and in only extremely rare cases has histological malignancy ensued. Because of the anatomic location, however, it cannot generally be completely excised.

Cerebellar Pilocytic Astrocytoma

The cerebellar astrocytoma is a well-circumscribed, often cystic, mass in the hemisphere or, less commonly, the vermis. Like the hypothalamic glioma, the neoplasm is remarkable microscopically for elongated areas of cellular polarity alternating with large or small areas of spongy microcystic change. The nuclei are characteristically uniform and euchromatic. Rosenthal fibers, calcium, and microvascular proliferation are frequently found. In common with the optic nerve and hypothalamic astrocytomas, cells closely resembling oligodendrocytes are often seen.

This classic lesion grows slowly and is amenable to total resection because of its location and circumscribed nature. Long survivals have followed even subtotal resections.

Pilocytic Astrocytomas of the Cerebral Hemispheres and Spinal Cord

Although pilocytic astrocytomas are most commonly encountered at the sites discussed above, they also not infrequently occur in the cerebral hemispheres and in the spinal cord. An awareness of the existence of cerebral hemisphere and spinal cord pilocytic astrocytomas is essential to facilitate accurate diagnosis and to minimize the possibility of mistaking these tumors for the more aggressive well-differentiated fibrillary astrocytomas or anaplastic astrocytomas.

Pilocytic astrocytomas of the cerebral hemispheres often present in adults, and exhibit similar neuroimaging characteristics to those found in other anatomic sites, i.e., contrast enhancement and a prominent cystic component. The histologic features are those common to other pilocytic astrocytomas: biphasic composition with bundles of elongated neoplastic pilocytic astrocytes interspersed between loose, microcystic areas of small stellate astrocytes, Rosenthal fibers, and eosinophilic granular bodies. Both microvascular proliferation and occasional marked nuclear pleomorphism may be present (accounting for the tendency to "over­grade" these lesions as anaplastic astrocytomas), but mitotic figures are very infrequent.

Pilocytic astrocytomas with the typical constellation of histologic features also occur in the spinal cord, where they are usually well circumscribed on magnetic resonance imaging studies and may be amenable to surgical cure. As with pilocytic astrocytomas of the cerebral hemispheres, a principal requirement for diagnostic recognition is an awareness of the existence of this unique class of astrocytomas at this anatomic site.

Pleomorphic Xanthoastrocytoma

The pleomorphic xanthoastrocytoma (PXA) was first identified as a distinctive astrocytic neoplasm with a comparatively good prognosis by Kepes et al. in 1979. The typical clinical presentation is that of a young adult (most commonly in the second decade) with a long-standing history of seizures. Pathomorphologic features include superficial cortical location (most frequently in the temporal lobe) with leptomeningeal involvement, striking tumor cell pleomorphism, an abundant reticulin meshwork enveloping the neoplastic cells, and frequent (but not invariably present) lipidization of tumor cells. Significantly, there is a very low mitotic rate and necrosis is absent. The morphologic features of PXA are quite similar to those of meningeal sarcoma and giant cell glioblastoma, two entities that carry worse prognoses. PXA is differentiated from malignant mesenchymal mimics by demonstration of tumor cell immunopositivity for GFAP. The separation from more malignant astrocytic neoplasms is based on both clinical characteristics, such as the typically young age of the patient, and, histologically, the lack of tumor necrosis and paucity of mitotic activity. Exclusion of glioblastoma on purely morphologic grounds by examination of limited tissue samples, such as those obtained by stereotactic needle biopsy, may not be possible and caution is warranted in such cases, particularly in the presence of features that are at variance with the typical presentation such as older patient age or atypical tumor location. The presence of numerous mitotic figures, in particular, should heighten suspicion of a more aggressive neoplasm.

The generally favourable prognosis for PXA patients, with extended survival for many years or even decades, has been well documented (it is, indeed, the most compelling justification for recognition of PXA as a distinctive class of astrocytic neoplasm). However, instances of early recurrence and malignant evolution of PXA (in some cases more than 10 years after initial diagnosis) have been reported. Although it is possible that some of these cases may represent misidentified malignant astrocytomas, others seem to be thoroughly evaluated bona fide examples. The PXA is therefore best viewed as a strikingly pleomorphic low-grade astrocytic tumor with a comparably favourable prognosis for extended survival, but which, like other classes of low-grade astrocytoma, has the potential for recurrence and, in some cases, malignant progression.