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