MACROSCOPIC APPEARANCES

Ganglion cell neoplasms are generally circumscribed; only rare examples have a diffuse glial element (Fig. 37.1). They are usually firm and gray, and frequently contain flecks of calcification and small cysts. They may appear as a mural nodule in a large cyst.

MICROSCOPIC APPEARANCES

Cursorily, neoplastic ‘ganglion’ cells look like large neurons, possessing a round nucleus, prominent nucleolus, and Nissl substance, but many have obvious cytologic atypia on closer inspection. Their distribution is characteristically disorganized. Ganglion cell neoplasms exhibit a range of histologic appearances; ganglion cells may either dominate the picture or be part of a polymorphous population of cells.

Gangliocytomas consist of disorganized ganglion cells set against a neuropil-like background or a lacy, fibrillary background containing a few reactive astrocytes (Fig. 37.2). Groups of ganglion cells may appear in nests enclosed by thin fibrovascular septa. In some cases, extensive desmoplasia may surround elongated cells that have a neuronal immunophenotype. Neoplastic ganglion cells possess abnormal, thickened processes and some have double nuclei. Small round cells with a relatively high nuclear:cytoplasmic ratio, but without nuclear hyperchromasia, represent a further neuronal phenotype encountered in these neoplasms (Fig. 37.2).

Gangliogliomas also contain neoplastic glial cells, which may greatly outnumber the ganglion cells. Neoplastic glia in gangliogliomas may have an obvious astrocytic morphology, but some ganglion cell neoplasms contain cells of an indeterminate nature (Figs 37.3, 37.4). While the glial component of some gangliogliomas appears as a fibrillary astrocytoma, other gangliogliomas manifest as a pilocytic astrocytoma or pleomorphic xanthoastrocytoma with a ganglion cell component. Eosinophilic granular bodies and neovascularization, of the type seen in pilocytic astrocytomas, may be evident. Degenerative cytologic changes take the form of nuclear pleomorphism and hyperchromasia, in the absence of mitoses. Some gangliogliomas are focally desmoplastic, or may spread into the subarachnoid space, provoking desmoplasia.

Ganglion cell neoplasms may contain aggregates of lymphoid cells, many of which are perivascular. Finding a mitotic figure in a ganglion cell neoplasm is unusual. If mitoses accompany cytologic pleomorphism in the glial element of a ganglioglioma, the possibility of its anaplastic transformation should be considered. However, this event occurs in less than 5% of gangliogliomas, and it is important to recall that invasion of gray matter by an anaplastic astrocytoma enters the differential diagnosis of these histopathologic features.

Ganglion cells are immunoreactive for NEU-N, synaptophysin, and neurofilament proteins (Fig. 37.4). Electron microscopy reveals dense-core synaptic vesicles.

Small round undifferentiated cells with a high nuclear:cytoplasmic ratio and nuclear hyperchromasia are combined with ganglion cells in the ganglioneuroblastoma, which is regarded as a variant of PNET (Fig. 37.5). Mitoses and apoptotic bodies are usually identifiable among the small cells. Recognition of the embryonal element is important because its presence confers a much poorer prognosis and has implications for therapy. The combination of neoplastic neuronal and glial cells that are both undifferentiated and differentiated (i.e. ganglioneuroblastoma/glioblastoma, or malignant glioma/PNET) is recognized as an entity, but extremely rare. Like the ganglioneuroblastoma, these neoplasms should probably be regarded as variants of PNET.

MACROSCOPIC APPEARANCES

The desmoplastic nature of a DIGG gives it a firm texture. Part of the neoplasm may lie in the subarachnoid space and be attached to the dura. Cysts are usually evident, and a single cyst may occupy a large volume.

MICROSCOPIC APPEARANCES

In areas of prominent desmoplasia, neoplastic glial cells are spindle-shaped with elongated hyperchromatic nuclei (Fig. 37.6). In some areas, the fascicular architecture and desmoplasia give way to foci of plump astrocytic cells or even limited numbers of poorly differentiated neuroepithelial cells. Ganglion cells with large nuclei are found within DIGGs (Fig. 37.6), but not DIAs, and can be numerous, mimicking a ganglioglioma. A small number of mitoses with a normal configuration may be present among the poorly differentiated cells.

Immunohistochemistry shows that many cells express GFAP. Synaptophysin and neurofilament antibodies label ganglion cells and some cells without obvious neuronal morphology. Ultrastructural examination reveals that many of the astrocytic cells have a prominent basal lamina.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The central neurocytoma is a soft, well-circumscribed neoplasm that often contains flecks of calcification. It consists of monotonous round to oval cells, which have fibrillary cytoplasm and round nuclei with finely granular chromatin (Fig. 37.8). A fixation artifact giving a ‘fried egg’ appearance to the cells is sometimes seen. The sheet of neoplastic cells is divided by anuclear fibrillary zones, which contain fine capillaries. Mitotic figures are seldom seen. Rarely, ganglion cells are present, evincing the neuronal lineage of the neoplasm.

Reports of a few central neurocytomas with a relatively high Ki-67 immunolabeling index or foci of vascular proliferation and necrosis have introduced the concept of ‘atypical’ neurocytomas, but several years of recurrence-free survival are possible even if a tumor shows these features.

Immunohistochemistry reveals synaptophysin in the cell bodies/ fibrillary matrix. GFAP antibodies label reactive astrocytes and a few neoplastic cells in about 10% of tumors. Neurofilament protein is demonstrable in the occasional ganglion cell. Ultrastructurally, the cells contain microtubules and a few dense-core secretory vesicles.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The liponeurocytoma tends to be well circumscribed and soft, not unlike a central neurocytoma. It is composed of sheets of monomorphic neurocytic cells with round or oval nuclei, which are admixed with groups of lipidized tumor cells (Fig. 37.9). Immunohistochemistry reveals a neuronal phenotype in most cells, but the reactivities for synaptophysin and MAP-2 are usually supplemented by labeling of a few tumor cells for GFAP. The Ki-67 labeling index is characteristically low.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

PGNTs can be solid or cystic and often show focal calcification. At the microscopic level, there is a pseudo-papillary architecture characterized by discohesive elements centered on hyalinized blood vessels. Small, poorly differentiated, GFAP-immunopositive cells with round nuclei and a high nuclear:cytoplasmic ratio have a perivascular distribution, but give way to interpapillary groups of cells with a (mainly neurocytic) neuronal morphology and immunophenotype. Mitoses are rare, and necrosis and microvascular proliferation are not features of the neoplastic process (Fig. 37.10).

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The RGNT is a circumscribed tumor, with restricted infiltration on microscopy. Two histological elements are present: neuronal and glial. Small uniform neurocytic cells form ring-like rosettes, usually with a core of dense synaptophysin-positive neurofibrillary material, or cluster around capillaries. Microcystic degeneration of the focally myxoid matrix may occur. The glial element resembles a pilocytic astrocytoma (Fig. 37.11).

MACROSCOPIC AND MICROSCOPIC APPEARANCES

Paraganglioma of the filum terminale is an encapsulated neoplasm arising from the filum terminale or lumbosacral roots and forming a lozenge-shaped structure. It appears richly vascular and may be cystic.

Microscopically, nests of oval or polyhedral cells with granular cytoplasm are surrounded by a delicate fibrovascular network (Fig. 37.12). Some cytologic pleomorphism may be apparent, but is of no biologic significance. Nuclei contain stippled chromatin. Ganglion cells may make up a large proportion of the cells (gangliocytic paraganglioma).

Immunoreactivity for synaptophysin and chromogranin is present, and ultrastructural examination reveals dense-core granules. Sustentacular cells at the periphery of the cell nests are immunoreactive for S-100 protein.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

DNTs usually display a distinctive multinodular architecture. They may occupy a small or a large area of cerebral cortex, and involved gyri are often protuberant. Involvement of subcortical white matter is unusual and not extensive.

DNTs are currently divided into two forms: simple and complex (Figs 37.13, 37.14). Both have the characteristic ‘specific glioneuronal element’, which has a nodular architecture and contains masses of oligodendrocyte-like cells (OLCs). The OLCs are set against a mucinous matrix, in which microcyst formation occurs. Focally, the OLCs have a columnar arrangement and seem to be suspended from neuritic processes or capillaries. Small cysts sometimes contain a mature neuron, which appears suspended (sometime described as ‘floating’) in a mucopolysaccharide-rich medium. The complex form also includes groups of glial cells, often with a nodular architecture. In isolation, the glial cells have the features of an astrocytoma, oligodendroglioma, or mixed glioma. Focal calcification is seen in some DNTs.

The surrounding cortex, which may show discrete areas of dysplasia, is diffusely invaded by OLCs, but perineuronal satellitosis is not a prominent feature. Dystrophic calcification may be seen, but mitoses are rare.

Immunohistochemistry and ultrastructural examination reveal that few OLCs have a neuronal or astrocytic phenotype, though they have been regarded as neuroepithelial cells capable of divergent differentiation on the basis of these analyses. The larger cells in the glioneuronal element are immunoreactive for neuronal markers, such as synaptophysin and neurofilament proteins. Glial cells are usually immunoreactive for GFAP. The growth fraction, as assessed with Ki-67 antibodies, is usually below 1%, but not zero.

MACROSCOPIC AND MICROSCOPIC APPEARANCES

The folia within a dysplastic gangliocytoma of the cerebellum appear abnormally thickened (Fig. 37.15a). Enlarged abnormal neurons replace internal granule cells, distorting the normal cerebellar architecture (Fig. 37.15b). The cells are immunoreactive for synaptophysin and neurofilament proteins and their axons in the molecular layer are often myelinated. There is a loss of Purkinje cells and rarefaction or cavitation of white matter in the core of affected folia.