Gangliogliomas involving the optic chiasm

Gangliogliomas are CNS neoplasms, containing neuronal and glial elements, that make up 0.4 to 0.6% of all brain tumors but represent 1.2 to 7.6% of childhood brain neoplasms. ^[1] These tumors may arise anywhere in the neuroaxis but are more common in the cerebral hemispheres and spinal cord. ^[2] Patients usually present with intellectual and behavioral abnormalities, seizures, or focal neurologic deficits. ^[3] Ganglioneuromas are histologically similar tumors found in the peripheral nervous system, although previous authors have used the term interchangeably.

Gangliogliomas involving the anterior visual pathways are uncommon. ^[4] Herein we report three patients with gangliogliomas involving the optic chiasm.

Case Reports.

Patient 1.

A 13-year-old girl diagnosed at age 2 with cerebral palsy, mild developmental delay, and complex partial seizures had not undergone previous neuroimaging. There was a 5-day history of visual difficulty OS followed by complete visual loss in that eye for 1 day. Visual acuity was 20/200 OD, no light perception OS. Confrontation field testing revealed only a temporal island of vision OD. The pupil OS was amaurotic. Eye movements were normal, and funduscopy revealed bilateral pale disk swelling and tortuosity of the retinal vessels. She had poor short-term memory, and a mild left-sided hemiparesis involving face, arm, and leg, and left hyperreflexia.

Neuroimaging revealed a large, heterogeneous, infiltrative mass involving the medial right temporal lobe, chiasmatic suprasellar region, prepontine cisterns, basal ganglia, and a portion of the right thalamus Figure 1. With MRI, the mass was mostly hypointense on T₁-weighted images and hyperintense on T₂-weighted images. Compression of the right cerebral peduncle and hydrocephalus were present. Nodular enhancement of both optic nerves, the optic chiasm, the left cerebellopontine angle, and spinal cord at the cervicomedullary junction, T-3, T-6, and T-12 were noted along with diffuse coating of the spinal cord, indicating tumor dissemination (see Figure 1).

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Figure 1. Patient 1. Right temporal lobe calcified ganglioglioma with extent into the suprasellar cistern and with distal subarachnoid spread. (A) Coronal contrast-enhanced MR shows the large mass involving the right temporal lobe and the right thalamus and infiltrating the suprasellar cistern with encasement of the chiasm (solid arrow). The tumor (open arrow) also extends to the left side of the brain. There is moderate hydrocephalus. (B) Contrast-enhanced MR of the spine shows coating of the spinal cord by the enhancing tumor (arrows).

A biopsy and subtotal tumor resection of the temporal lobe mass were performed, and a ventriculoperitoneal shunt was placed. Pathologic examination revealed a histologically benign, partially calcified tumor composed of astrocytes and abnormal neurons and characteristic of a ganglioglioma Figure 2. Three weeks postoperatively the patient became blind in both eyes despite a functioning shunt (ventricle size had returned to normal) and tumor debulking.

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Figure 2. Patient 1. (A) Photomicrograph of typical field of temporal lobe ganglioglioma showing relative hypocellular field characterized by random distribution of astrocytes and ganglion cells (black arrow points to a ganglion cell). H-E stain. (B) Photomicrograph of a different field from same tumor showing preponderance of glial cells with small nuclei, irregular deposits of calcospherites, and a bizarre ganglion cell in the center of the field (black arrow). Immunoperoxidase technique for neurofilament protein (NFP).

The patient was observed without treatment. Eight months postoperatively she developed back pain, gait difficulty, and constipation. MRI demonstrated worsening hydrocephalus and more extensive spinal subarachnoid spread of tumor. The ventriculoperitoneal shunt was revised with significant resolution of symptoms. Chemotherapy with oral VP-16 (etoposide) was begun.

Patient 2.

A 6-year-old boy had persistent headaches and vomiting, and CT revealed a suprasellar mass with cystic components and third-ventricular compression. MRI demonstrated chiasmal enlargement with gadolinium enhancement and cysts superior and inferior to the chiasm Figure 3. Biopsy revealed a ganglioglioma, and the patient received radiation therapy (5,580 cGy). He eventually required growth hormone, leuprolide, and vasopressin.

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Figure 3. Patient 2. Ganglioglioma of the hypothalamus and chiasm. (A) Coronal contrast-enhanced MR shows a mass that has a contrast-enhancing component (white arrows) within the chiasm and a nonenhancing cystic-appearing component (black arrow) in the hypothalamus. (B) Contrast-enhanced sagittal MR shows prominent enhancement of the suprasellar component (arrow). (C) Follow-up imaging 3 years later shows decrease in the contrast-enhancing portion of the mass. Note the cysts (open arrows) above and below the chiasm. However, there is a new cystic component (solid arrow) present anterior to the contrast-enhancing component.

Five months after discovery of the mass, his visual acuity was 20/25 OD, 20/60 OS. He had mild dyschromatopsia OS. A right afferent pupillary defect was present, and the right optic disk was pale. Three months later kinetic perimetry disclosed a temporal defect OD (greatest inferiorly), and a central temporal defect OS. His neurologic examination was otherwise normal.

Over the next 5 years the neuro-ophthalmic examination remained basically unchanged. The only exception was a small-amplitude, vertical pendular nystagmus OS>OD, which occurred in bursts, beginning at age 9. At age 11, visual acuity was 20/20 OD, 20/70 OS. He saw 9/9 color plates OU. Kinetic perimetry confirmed the static nature of the bitemporal hemianopsia. Both optic disks were pale. On serial neuroimaging, the cysts and the contrast-enhancing portion decreased in size, but there was a new cystic component anteriorly (see Figure 3).

Patient 3.

A 23-year-old man had 1 year of behavioral changes, weight gain, and increased appetite. Visual acuity was 20/40 OD and 20/25 OS, and the neurologic examination was remarkable for a blunt affect and a slow response to questions. CT and arteriography suggested hydrocephalus due to a third-ventricular mass. A partial excision via a left frontal craniotomy was performed. Histopathologic examination revealed abnormal neurons and astrocytes surrounded by a prominent fibrovascular stroma, consistent with a ganglioglioma. Nissel and Bodian stains confirmed the presence of neurons. Persistent hydrocephalus necessitated ventriculoperitoneal shunting. Radiation therapy was administered.

At age 26, the visual acuity fell to 20/80 OD, 20/40 OS, with marked dyschromatopsia OU. Kinetic perimetry demonstrated an inferior arcuate scotoma and infranasal constriction OD and diffuse constriction OS. Both optic disks were pale. CT demonstrated bilateral optic tract enhancement.

At age 32 MRI demonstrated a cystic hypothalamic mass that abutted the optic chiasm on the left and infiltrated the optic tracts bilaterally Figure 4. At age 35, visual acuity was counting fingers at 3 feet OD and 5/200 (temporally) OS. At age 36, visual acuity was 2/200 OD, 3/200 OS. MRI was unchanged.

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Figure 4. Patient 3. Ganglioglioma involving chiasm and optic tracts. (A) Contrast-enhanced axial MR at the level of the chiasm shows a partially enhancing mass (thick black arrow). A portion of the mass (white arrow) that is nonenhancing has extended into the medial aspect of the left temporal lobe. A portion of the optic tract (thin black arrow) can be identified on the right side. (B) Follow-up axial contrast-enhanced MR performed 8 years later shows no change in the enhancing portions but enlargement of the component within the medial left temporal lobe. There is partial enhancement of the right optic tract (black arrow). There is also a nonenhancing component of the tumor in the region of the right lateral geniculate nucleus (white arrow).

At age 40, visual acuity was counting fingers at 1 foot OD and counting fingers at 6 inches OS. Kinetic perimetry demonstrated small left homonymous islands of vision. He took diphenylhydantoin for seizures and thyroxine for hypothyroidism. MRI demonstrated enlargement of the cystic component of the tumor on the left (see Figure 4).

Discussion.

The gangliogliomas in these patients involved the chiasm via three distinct mechanisms. Patient 1 had unique tumor invasion of optic nerves and chiasm by medial extension of a temporal lobe ganglioglioma into the suprasellar area. Her prolonged neurologic symptoms and the large size of her tumor suggest that the neoplasm may have been present in the temporal lobe for many years but became apparent only when visual symptoms occurred. Involvement of the chiasm in this manner must be considered rare. The ganglioglioma in patient 2 was intrinsic to the hypothalamus and chiasm, while the tumor in patient 3 invaded both optic tracts with lateral compression of the chiasm by a cyst. Patient 2 had a bitemporal hemianopsia, while the other two had severe bilateral visual loss: Patient 1 was completely blind, and patient 3 had markedly reduced acuity and residual left homonymous islands of vision. All patients had bilateral optic atrophy.

Although gangliogliomas may arise from the floor of the third ventricle, ^[5] only a few cases of extrinsic chiasmal compression by these tumors are reported in detail. In Courville's seminal description, ^[6] he summarized a case of a 16-year-old girl with headaches, blindness, and a right hemiparesis. Autopsy disclosed a "firm tumor, the size of a plum, situated between the diverging limbs of the optic tracts,'' consistent with a ganglioneuroma arising from the tuber cinereum. Pituitary or hypothalmic dysfunction, sometimes accompanied by visual loss due to obstructive hydrocephalus and chronic papilledema, is the more common presentation of gangliogliomas in this region. ^[7]

Gangliogliomas intrinsic to the chiasm are also unusual. In 1990 Chilton et al. ^[4] reported a 33-year-old man with a ganglioglioma of the optic chiasm and right optic tract; they found only a few other well-documented cases with clinicopathologic correlation. Cogan et al. ^[8] described a 10-year-old girl with a ganglioneuroma "the size of a golf ball within the chiasm, extending into the right optic nerve.'' The patient had light perception vision OD and 20/100 acuity OS. Lowes et al. ^[9] reported two other patients, ages 16 and 24, each with bilaterally reduced visual acuity and bitemporal hemianopsias, and Doyle and Kernohan ^[10] described another. There are two further reports of gangliogliomas involving the entire pregeniculate pathway. ^[11,12] There have been three complete descriptions of gangliogliomas solely of the optic nerve. ^[13-15] Since the optic nerve and chiasm do not contain neuronal cell bodies, these gangliogliomas may have arisen from ectopic neural tissue ^[15] or more primitive neurons, ^[14] or spread from the floor of the third ventricle. ^[10] Because of their indolent visual loss associated with optic nerve or chiasmal enlargement, gangliogliomas intrinsic to the anterior visual pathway may mimic optic gliomas (juvenile pilocytic astrocytomas) clinically and radiologically.

Gangliogliomas are usually slowly growing neoplasms, and occasionally behave like hamartomas. In some instances, gangliogliomas may arise during neural development, and as in patient 1, long intervals between the appearance of symptoms and detection of the gangliogliomas may occur. ^[16] In most instances of tumor progression, it is the glial component that becomes anaplastic, although in exceptional circumstances, the ganglion cells undergo transformation to more primitive neuroectodermal cells. Subarachnoid dissemination to the spine in patient 1 could represent anaplasia of the astrocytic component or simply join a small group of cases in which histologically benign glial tumors metastasize in a histologically malignant manner. ^[17] Gangliogliomas with dissemination at presentation are unusual.

When surgically accessible, complete resection is usually curative, with radiation and chemotherapy reserved for cases with progression or recurrence. ^[3,18,19] Because of chiasmal and hypothalamic involvement, complete surgical resection in our patients was not possible. In patient 2, his condition has remained clinically and radiologically stable for 5 years following radiation therapy. However, the ganglioglioma of patient 1 acted aggressively, and the condition of patient 3 has slowly worsened despite radiation, in part because of an enlarging cystic component. Of the reported patients with long term follow-up, ^[8,9] two had conditions that stabilized following radiation therapy, while one continued to lose vision. Thus, the prognosis for patients with gangliogliomas involving the chiasm may be quite varied.