Gangliocytoma and ganglioglioma are well-differentiated tumors composed of mature neurons alone or neurons combined with glial cells, frequently occurring in the temporal lobe. Ganglioglioma is the most common tumor associated with chronic temporal lobe epilepsy. Dysembryoplastic neuroepithelial tumor is a low-grade tumor that occurs in children with long-standing seizures, characterized by multinodular architecture and glioneuronal elements in cystic spaces. Central neurocytoma is a low-grade neuronal tumor typically located in the ventricles that can be cured by surgery for small lesions but recurs with partial resection.

1. NEURONAL AND MIXED NEURONAL-GLIAL TUMORS Gangliocytoma (WHO grade I) and
ganglioglioma (WHO grade I or III) are well-differentiated tumors composed of neoplastic
mature-appearing neurons alone (gangliocytoma) or neoplastic ganglion cells combined
with glioma cells (ganglioglioma). They frequently occur in the temporal lobe. Ganglioglioma
is the most common tumor associated with chronic temporal lobe epilepsy (40% of tumor-
associated temporal lobe epilepsy cases). Both tumors are grossly circumscribed, may be
solid or cystic, and frequently contain calcifications. At the microscopic level, gangliocytoma
is composed entirely of clusters of dysmorphic mature ganglion cells (Fig. 96-4), whereas the
ganglion cells in ganglioglioma are accompanied by glioma elements (usually astrocytoma).
The glial component may include cell types resembling pilocytic astrocytoma (with
Rosenthal fibers and EGBs), fibrillary astrocytoma, or rarely, oligodendroglioma. In the latter
two cases, ganglioglioma has the potential to undergo anaplastic progression.
Ganglioglioma must be differentiated from the cortical invasion of diffuse astrocytoma with
entrapped neurons. Lymphocytic perivascular infiltrates are common. Immunopositivity for
neuronal markers, such as synaptophysin and NeuN, in a subpopulation of tumor cells is
characteristic. Another helpful marker is the oncofetal CD34 antigen, which is expressed in
the neural component of gangliogliomas but not in normal brain. Dysplastic gangliocytoma
of the cerebellum (LhermitteDuclos disease; WHO grade I) is a distinctive clinicopathologic
entity that is characterized by a cerebellar location, gross enlargement of the folia on MRI,
and a disorganized cerebellar cortical histology in which large ganglion cells predominate. A
layer of myelinated axons in the outermost part of the molecular layer just beneath the pia
is also a distinctive feature. An association with Cowden syndrome is observed in 50% of
patients. Complete surgical resection is curative. Dysembryoplastic neuroepithelial tumor
(DNT; WHO grade I) is a low-grade quasihamartomatous tumor that occurs in children and
young patients with a history of long-standing resistant seizures. Neither mass effect nor
peritumoral edema is observed on neuroimaging studies. Characteristic features of DNT
include a multinodular architecture and a predominantly intracortical location. The
temporal lobe is the preferred location, but DNT can arise in any part of the supratentorial
cortex. The rostral septum pellucidum/head of the caudate nucleus/frontal horn of the
lateral ventricle region is an additional rare but well-recognized site of occurrence. The
specific glioneuronal element is considered the histologic hallmark of DNT and consists of
prominent clusters of oligodendroglial-like cells with interspersed neurons that often
appear to float in the cystic spaces of the loose background stroma. DNT closely mimics low-
grade oligodendroglioma. Foci of cortical dysplasia may be identified in the adjacent
peritumoral cortex. Resection is curative, and even partial resection usually stops the
seizure activity. Central neurocytoma and extraventricular neurocytoma (WHO grade II) are
low-grade neoplasms of young adults, composed of re markably monomorphous round cells
with immunohistochemical and ultrastructural evidence of neuronal differentiation.
Neurocytomas are typically located in the lateral ventricles or third ventricle, or both, with
an attachment to the septum pellucidum. Neoplasms with similar histopathologic
characteristics and biologic behavior occur outside the ventricular system. Diffuse positivity
for synaptophysin is the rule. Surgery can be curative with small lesions, but local
recurrence results with partially resected tumors. Increased mitotic activity and vascular
proliferation may rarely be seen but are not generally associated with a poor prognosis.
Atypical neurocytomas are defined by an increased Ki-67 antigen (MIB-1 antibody) labeling
index of greater than 2%, and these tumors have an increased likelihood of recurrence.

2. Rare tumors consisting of neurocytic cells with focal areas of lipomatous differentiation
resembling mature adipose tissue typically occur in the cerebellum of adults and are
designated cerebellar liponeurocytoma (WHO grade II). Paraganglioma of the filum
terminale (WHO grade I) is an uncommon neuroendocrine tumor that arises from the conus
medullaris/filum terminale region. As seen histologically, paragangliomas of the filum
terminale can mimic ependymoma, with perivascular pseudorosette formation. Strong
tumor cell positivity is seen for neuronal markers such as synaptophysin. Most tumors are
encapsulated by an investing layer of leptomeninges and may be cured by total excision.
Papillary glioneuronal tumor (WHO grade I) and rosetteforming glioneuronal tumor of the
fourth ventricle (WHO grade I) are both rare mixed neoplasms that have recently been
codified as new entities by the WHO. Papillary glioneuronal tumor is a supratentorial lesion
(often temporal) histologically characterized by pseudopapillary structures of cuboidal glial
cells surrounding hyalinized vessels, with the intervening zones filled with neurocytic
elements. The cells in direct contact with the vessels are GFAP-positive, whereas cells
without vascular association stain for synaptophysin. Rosette-forming glioneuronal tumor of
the fourth ventricle is a tumor of children and young adults. The neuronal component
consists of neurocytes that form rosettes with eosinophilic, synaptophysin-positive
avascular cores, and the glial component typically exhibits features of pilocytic astrocytoma.
Both papillary glioneuronal tumor and rosette-forming glioneuronal tumor of the fourth
ventricle are clinically indolent and surgically curable.