GANGLIOGLIOMAS

are unusual central nervous system tumors of children and young adults that are composed of both differentiated neurons and a background stroma of glial cells. The term was originally introduced by Courville in 1930; he thought that the tumor arose from undifferentiated cells that became neoplastic yet eventually differentiated along both glial and neuronal lines to achieve the mature forms of the cells. Because differentiation was complete, he thought that the tumor must be essentially benign. In the past, some authors have suggested that gangliogliomas are hamartomatous with limited growth potential. Most modern workers agree, however. that these are true neoplasms.

Pathologically, the diagnosis requires both astrocytic and neuronal cell populations to be present, although in most cases the astrocytic cell line will predominate. Some tumors will show foci of oligodendroglioma as well. In most instances, the appearance of neurons is abnormal for the location in which they are found, although in areas such as the thalamus and basal ganglia it may be difficult to ascertain whether the neurons are part of the neoplastic process or are simply normal neurons surrounded by neoplastic astrocytes. To be considered neoplastic, neurons must be either clearly heterotopic (located away from gray matter) or atypical, showing disorientation, bizarre shapes or sizes, or binucleation.

Within a ganglioglioma, calcification is frequent, as are cystic areas. Malignant gangliogliomas are unusual and when they occur, the malignant features are virtually always in the glial component. It is not known whether histologic evidence of malignancy in the astroglial component carries the usual poor outlook of the malignant glioma.

An incidence ranging from 0.4 percent in a large series of brain tumors to 7.6 percent in a series of paediatric brain neoplasms. The incidence seems to be increasing, as computed tomography (CT) scanning and magnetic resonance imaging (MRI) have allowed earlier diagnosis.

Clinical Presentation

The mean age at presentation is 12 years. with a predominance between 7 and 18 years. Adult patients are occasionally reported. A male predominance has been noted in one series.

The presenting symptoms are usually of long duration (average 1.5 years), although more recent patients are being diagnosed earlier as radiologic studies become more easily obtainable. Patients almost invariably present with seizures when the lesion is supratentorial. The seizures themselves are not particularly characteristic, and the specific type depends on the site of the lesion. Temporal lobe convulsions are frequent as gangliogliomas frequently occur in the temporal lobe, but grand mal, focal motor. and mixed types can occur. Seizures tend to worsen with time, and the diagnosis of a brain tumor is established when they become uncontrollable even with appropriate anticonvulsant medication. Focal neurologic deficits are unusual in hemispheric gangliogliomas, even when the lesion is located in an eloquent area, such as the motor cortex. Symptoms and signs of increased intra­cranial pressure such as headache, papilledema. or alteration in consciousness are rare, and usually occur in midline tumors. Patients may have evidence of a diffuse cerebral disturbance such as poor school performance or behavioural disturbances, but this may reflect frequent seizures or the effects of anticonvulsant medication. The predominance of seizures is probably a function of the slow-growing nature of this tumor, which also explains the lack of focal neurologic symptoms and signs of increased intracranial pressure.

Although gangliogliomas typically occur in the cerebral hemispheres, the tumor may arise in other locations. Courville presented several patients with a tumor arising from the region of the tuber cinereum who presented with hypothalamic symptoms or hydrocephalus. Various authors have described gangliogliomas arising in the cerebellum, brain stem, or spinal cord.

Radiologic Investigations

The radiologic manifestations of gangliogliomas were examined during the pre-CT era. The major features described were calcification on plain skull films (10 percent) and an avascular mass seen on angiography or pneumoencephalography. The appearance on CT scan is variable; gangliogliomas may be isodense, of increased density, or hypodense to the degree that they may be confused with CSF-containing arachnoid cysts or porencephalies. There are frequently areas of calcification. Many tumors will involve the cortical surface, and these tend to indent the inner table of the skull. Some contrast enhancement occurs in approximately one-half of patients.

MR images have proved useful in the diagnosis of ganglioglioma, and in some cases the diagnosis can be predicted preoperatively. The low-density tumors seen on CT have a decreased signal on T1-weighted images and are readily distinguished from CSF. On T2-weighted images, the lesions appear as discrete areas of increased signal intensity, and the appearance of swollen gyri can be seen on the cortical margin. With calcified lesions, MRI may be helpful in excluding vascular malformations. Sagittal and coronal images are helpful in identifying the relationship of the lesion to areas of eloquent cortex and in planning the operative exposure.

Treatment and Outcome

The mainstay of treatment is surgical excision, and gross total removal is possible in the majority. Despite the CT appearance of low density, the tumor is usually solid, although cystic areas may be present. Gangliogliomas of the temporal lobe, in particular, are more likely to be solid. Lesions that appear on the surface have the appearance of pale, swollen gyri that are readily separable from the adjacent normal brain at the intervening sulci. They tend to be avascular, and lumps of calcium may be evident. At the depths of the lesion the plane is often obscure, and it is advisable to be conservative in this part of the dissection, as these lesions may not recur, even if subtotally removed. Gangliogliomas may grow in inconvenient locations, such as the interhemispheric fissure, motor cortex, visual areas, or speech areas. The neoplasm itself subserves no neurological function and can be removed safely even from these areas, although one must expect transient neurologic deficit from retraction. Subcortical lesions are best localized intraoperatively using real-time ultrasound to minimize the size of the cortical incision and to ensure an adequate removal. Gangliogliomas of the medial temporal lobe are treated by formal temporal lobectomy as for a seizure disorder.

Postoperative radiologic evaluations of these patients have been a problem. The postoperative CT scan may appear indistinguishable from the preoperative study despite a total tumor excision, because the tumor cavity fills with CSF. Studies performed a year or more after tumor removal, however, will show the area of the operation to be much smaller, as brain tissue gradually fills in the cavity. Subsequent enlargement of this low-density area be­speaks recurrence and should lead to consideration of reexploration, especially if seizure control is failing. MRI is useful in evaluating the completeness of excision, in that residual or recurrent tumor will have different signal characteristics than CSF.

The outlook for this tumor is excellent if radical surgical excision can be accomplished. Patients with midline tumors are less likely to have total excision and the rate of tumor progression and recurrence is high. Seizure control tends to improve after surgery, sometimes dramatically, and it is often possible to reduce or even discontinue anticonvulsant medication. Most modern authorities reserve radiation therapy for gangliogliomas with frankly malignant features or those which recur and in whom reoperation is not practical.