Chapter 30 Management of Pineal Region Tumors

Pineal region tumors encompass a diverse group of tumors that can arise from pineal parenchymal cells, supporting cells of the pineal gland, or glial cells from the midbrain and medial walls of the thalamus. These tumors occupy a central position that is equidistant from various cranial points traditionally used as routes of exposure. The deep central location places these tumors in intimate contact with important components of the deep venous system that lie dorsally, including the vein of Galen, the precentral cerebellar vein, and the internal cerebral veins.¹ In some instances, there may be a dense attachment to these structures and the tela choroidea. The tumor is often fed by small-caliber branches of the posterior choroidal arteries and branches of the quadrigeminal arteries that generally do not supply any clinically significant areas of the brain.

Although pineal region tumors affect a relatively small number of patients, their variable histology and difficult surgical challenge has generated a comparatively large volume of literature. This difficulty is underscored by Cushing’s statement: “Personally, I have never succeeded in exposing a pineal tumor sufficiently well to justify an attempt to remove it.”² Over the years, various supratentorial and infratentorial approaches have been developed by several prominent neurosurgeons including Dandy’s interhemispheric approach,³ Van Wagenen’s transventricular approach,⁴ and Poppen’s occipital transtentorial approach.⁵ The supracerebellar infratentorial approach was first described in 1926, when Krause reported three cases, each a different variety of tumor in the pineal or quadrigeminal region, which he approached through the posterior fossa, over the cerebellar hemispheres, and under the tentorium.⁶

In the 1970s, the increasing use of the operating microscope rekindled interest in direct surgical approaches to the pineal region.⁷^–⁹ This led to considerable debate over the best surgical route to the pineal region. More important than the route, however, was that debates stimulated interest in operating on these tumors to identify their nature and remove them whenever possible.^10,¹¹ The more aggressive approach to pineal region tumors resulted in greater awareness of the histologic diversity of these tumors existing along an extensive continuum from benign to highly malignant.¹² Some of these tumors are mixed in nature, simultaneously containing benign as well as malignant elements or even glial and pineal cell constituents.¹³ Despite advances in radiographic imaging and increased experience with tumor markers, preoperative diagnostic tests are insufficient and accurate determination of histologic typing requires operative intervention. With experience, the mortality and morbidity rates from the various surgical approaches dropped steadily and led to the current management philosophy for pineal tumors, which relies on an aggressive surgical approach for the removal of benign tumors and decompression and accurate histologic diagnosis of malignant tumors.¹⁴

Clinical Features

Pathology

The various cell types that comprise the mature pineal gland account for the diversity of histologic tumor subtypes that can occur in the pineal region. Lobules of pinealocytes surrounded by astrocytes form the pineal parenchyma with ependymal cells of the third ventricle lining the anterior border of the gland. Pineal tumors are grouped into four main categories:¹ germ cell tumors,² pineal cell tumors,³ glial cell tumors, and⁴ miscellaneous tumors (covering a wide range of histology). Each category contains tumors existing along a continuum from benign to malignant and can include mixed tumors of more than one cell type.¹⁵ The term pinealoma was originally used by Krabbe and is a misnomer because it originally pertained to germ cell tumors.¹⁶ Eventually this term was applied more generically to refer to any tumors of the pineal region. The term is now obsolete, in favor of pineal region tumors when a general reference is desired or an individual tumor’s histology in that region when specificity is preferred (e.g., astrocytoma of the pineal region).

Presentation

Tumors in the pineal region, regardless of their histology, generally become symptomatic by three mechanisms:¹⁵

1. Increased intracranial pressure from hydrocephalus.

2. Direct cerebellar or brain stem compression

3. Endocrine dysfunction

Headache, the most common presenting symptom, occurs after obstruction of the third ventricle outflow at the sylvian aqueduct. More advanced hydrocephalus can result in nausea, vomiting, papilledema, obtundation, and other cognitive deficits.

Direct brain stem compression may lead to disturbances of extraocular movements, classically known as Parinaud’s syndrome.¹⁷ Involvement of the superior cerebellar peduncles can lead to ataxia and dysmetria. Hearing disturbances can occasionally occur, probably from compression of the inferior colliculi.¹⁸

Endocrine dysfunction is rare and may be caused by direct tumor involvement in the hypothalamus or from secondary effects of hydrocephalus.¹⁹ Diabetes insipidus and other neuroendocrine disturbances are often indicative of hypothalamic infiltration by tumor, even when not radiographically visualized.

Laboratory Diagnosis

α-Fetoprotein and β-hCG are markers of germ cell malignancy and should be measured in serum and cerebrospinal fluid, if possible, as part of the preoperative workup in all pineal region tumor patients.^14,^20,²¹ Elevation of germ cell markers is pathognomonic for the presence of a malignant germ cell tumor, and under these circumstances, histologic verification is unnecessary as surgery does not improve the outcome with radiation and chemotherapy.²² In patients with marker-positive germ cell tumors, measurement of marker levels can also be useful to monitor therapeutic response and as a sensitive early sign of tumor recurrence. The absence of germ cell markers should be interpreted cautiously because malignant germ cell tumors such as germinomas and embryonal cell carcinomas cannot be ruled out.

α-Fetoprotein, normally associated with fetal yolk sac elements, is markedly elevated with endodermal sinus tumors, whereas smaller elevations occur with embryonal cell carcinomas and immature teratomas. β-hCG, normally secreted by placental trophoblastic tissue, is markedly elevated with choriocarcinomas, with smaller elevations associated with embryonal cell carcinomas and those occasional germinomas containing syncytiotrophoblastic giant cells.²³ Most germinomas are nonsecretory and carry a better prognosis than β-hCG positive germinomas.²⁴

Imaging

The standard diagnostic workup includes magnetic resonance imaging (MRI), with and without contrast, which has proven to be the most accurate diagnostic examination. MRI provides information on type, size, and extent of the tumor, as well as anatomic features such as degree of invasion, vascularity and the anatomic relationships of the tumor with its surroundings (Fig. 30-1). Some tumors can be suspected from the appearance of the scans, particularly teratomas, which contain multiple germ layers (Fig. 30-2). Angiography is only performed if the MRI suggests a vascular lesion such as a vein of Galen aneurysm or arteriovenous malformation. Despite this broad diagnostic armamentarium, the exact histologic nature of the tumor cannot be reliably determined without surgery.¹⁵

FIGURE 30-1 Sagittal magnetic resonance imaging with contrast shows a large pineal region tumor. The anatomic relationships of the tumor are well identified, including the third ventricle, aqueduct, and quadrigeminal plate.

FIGURE 30-2 Magnetic resonance imaging with contrast (axial view) demonstrates the typical variegated pattern of a mixed germ cell tumor of the pineal region. The heterogeneity of lesions such as this in the pineal region can lead to misdiagnosis from sampling error.

The increasing use of MRI has revealed a large number of patients with lesions of the pineal gland that are mostly cystic but contain a small amount of solid tissue (Fig. 30-3).^25,²⁶ In most cases, the aqueduct has not been compromised and the patients are not symptomatic from their lesion. Initially, they were considered to be low-grade cystic astrocytomas but, after surgical removal, were found to be composed of normal astrocytes and normal pineal cells. Histologically, these are pineal cysts and are normal anatomic variations of the pineal gland. As experience with pineal cysts has increased, it is clear that they should be managed conservatively with serial MRI scans and without surgery. Surgery is reserved for lesions that are symptomatic, progressing in size, or causing aqueductal obstruction.

FIGURE 30-3 Sagittal magnetic resonance imaging with contrast shows an incidental pineal cyst discovered during the workup for unrelated headaches. The aqueduct is not compromised, and there is no hydrocephalus. Pineal cysts are anatomic variants and do not require treatment except in rare instances when they become symptomatic.

Surgical Considerations

Surgical Anatomy

Most tumors arise from and are attached to the undersurface of the velum interpositum, which includes the choroid plexus, deep venous system, and choroidal arteries. Depending on the degree of invasion of these important midline structures, the attachment may be minimal or comprehensive. Tumors rarely extend above the velum interpositum for any significant distance. Therefore, the blood supply comes from within the velum interpositum, mainly through the posterior medial and lateral choroidal arteries with anastomoses to the pericallosal arteries and quadrigeminal arteries.^1,²⁷

Some tumors extend to the foramen of Monro, but most are centered at the pineal gland, extending to the midportion of the third ventricle and posteriorly to compress the anterior portion of the cerebellum. In rare instances, the internal cerebral veins are ventral to the tumor. Mostly, however, vein of Galen, internal cerebral veins, Rosenthal’s vein, and precentral cerebellar vein surround or cap the periphery of these tumors. The quadrigeminal plate may give rise to an exophytic astrocytoma or be infiltrated by the more malignant tumors of the pineal region, encompassing the aqueduct in the course of tumor growth. The most important aspects of the anatomy, which can be gleaned by radiographic imaging, are the relationship of the tumor to the third ventricle and quadrigeminal cistern, and the lateral and superior extent of the tumor. These features determine the route of the operation and the degree of difficulty likely to be encountered during surgery.¹

Management of Hydrocephalus

Most patients present with obstructive hydrocephalus, a problem that may be managed in several ways.¹⁴ When a complete tumor removal is anticipated and a permanent shunt may not be necessary, the hydrocephalus can be managed with a ventricular drain placed at the time of tumor surgery. The ventricular drain can be removed or converted to a permanent shunt on postoperative day 2 or 3, depending on which circumstances prevail. Occasionally, no drain is necessary and the hydrocephalus resolves after complete tumor removal. The drain can be removed or converted to a shunt in the postoperative period as the circumstances dictate. Patients with more advanced symptomatology should be managed with an image-guided stereotactic endoscopic third ventriculostomy to allow a gradual reduction in intracranial pressure and resolution of symptoms.²⁸ This method is preferable to ventriculoperitoneal shunting as it eliminates potential complications such as infection, overshunting, and peritoneal seeding of malignant cells.

Operative Approaches: Biopsy versus Open Resection

The wide diversity of pathology that can occur in the pineal region makes histologic diagnosis a necessity to optimize patient management decisions.¹⁴ Tissue histology has important implications for decisions concerning adjuvant therapy, metastatic workup, prognosis, and long-term follow-up. Cerebrospinal fluid cytology and radiographic examination are not sufficiently consistent to supplant the need for tissue diagnosis. The exception to mandatory histologic diagnosis is patients with elevated germ cell markers who can be treated with chemotherapy and radiation without a biopsy.^23,²⁹ Some of these patients require a delayed surgical resection to remove residual radiographic abnormalities that may represent residual tumor.³⁰

Specimens for tissue diagnosis can be obtained by either a stereotactic biopsy or an open operation. Passionate advocates for either approach can be found; however, it is important to recognize the relative advantages and disadvantages of each and use them in a complementary fashion for appropriate patients rather than having an inflexible dedication to one. The radiographic and clinical features of the tumor and the surgeon’s experience will influence procedural decisions.

Experienced neurosurgeons using current microsurgical techniques can expect favorable results with open surgery.¹⁴ Open procedures have the advantage of obtaining larger amounts of tissue to provide more extensive tissue sampling. This is particularly important for pineal region tumors where heterogeneity and mixed cell populations are common. This diversity is problematic for even experienced neuropathologists who can best resolve the subtleties of histologic diagnosis when free from the constraints of limited tissue sampling.³¹^–³³ Additionally, open procedures provide a clinical advantage by facilitating tumor removal.^14,^34,³⁵ This is particularly important for the one third of patients with benign pineal tumors, in whom resection is usually complete but can also be useful for patients with malignant tumors in whom debulking may provide a more favorable response to adjuvant therapy and a better long-term prognosis. Additional advantages of aggressive tumor debulking include the potential to relieve hydrocephalus without additional procedures and the ability to control the risks of postoperative hemorrhage into an incompletely resected tumor bed. A disadvantage of open procedures is the relatively higher surgical morbidity compared with that of stereotactic biopsy, at least in the short term. This short-term disadvantage, however, may be a reasonable concession for the long-term advantage of better tumor control.

Any discussion about the relative risks and benefits of open procedures must recognize that the highly favorable outcome for patient with pineal tumor assumes an advanced level of experience, judgment, and expertise. These sophisticated surgical procedures are not recommended for novice surgeons as they can expect significantly less favorable outcomes. Stereotactic procedures, in contrast, can be appealing because of their ease of performance; however, the pineal region is among the most hazardous areas in the brain to safely biopsy, and careful forethought must be given to planning the target and trajectory to minimize hemorrhagic risks.³⁶ The potential for hemorrhage is increased because of several mechanisms including bleeding from any of several pial surfaces that must be traversed, bleeding in highly vascular tumors, damage to the deep venous system, and bleeding into the ventricle where the tissue turgor is insufficient to tamponade minor bleeding.^37,³⁸ Despite this increased risk, several series have validated the effectiveness of stereotactic biopsy for these tumors.^36,³⁹

Stereotactic biopsy is ideally suited for patients with multiple lesions or clinical conditions that contraindicate open surgery and general anesthesia. Biopsy may also be preferable for tumors that are clearly invading the brain stem. However, the degree of invasion is not always easily discernible and tumors may have a surgically dissectible capsule that is not predicted on preoperative imaging studies.

Stereotactic Biopsy

Advances in radiographic imaging and software planning provide several alternatives for safely planning biopsy trajectories. Computed tomography-guided procedures are acceptable because of their high degree of accuracy and common availability. Although nearly any stereotactic frame system is sufficient, target-centered stereotactic frame systems such as the CRW (Cosman-Roberts-Wells) have the versatility to facilitate even complex biopsies. Local anesthesia with mild sedation is safe and usually sufficient to perform biopsies.

The most common surgical trajectory to the pineal region is via an anterolaterosuperior approach anterior to the coronal suture and lateral to the midpupillary line.⁴⁰ This trajectory passes through the frontal lobe and the internal capsule. The ependyma of the lateral ventricle and the internal cerebral vein should be avoided. An alternative approach is a posterolaterosuperior approach through the parieto-occipital junction, which is best suited for large tumors that have a lateral extension.

Whenever possible, multiple serial biopsy specimens should be obtained. Obviously, the risks of bleeding for each additional specimen must be considered, taking into account the size of the mass. A frozen section intraoperatively may be useful in verifying pathologic tissue; however, the high diversity of tissue types reduces the accuracy of a frozen tissue diagnosis.

Endoscopy

Advances in endoscopic technique have led to investigations of biopsies via this method.^41,⁴² Endoscopy is sometimes performed in conjunction with an endoscopic third ventriculostomy to relieve hydrocephalus. Performing a ventriculostomy and biopsy simultaneously requires the use of a flexible endoscope because of the limited trajectory to the tumor through Monro’s foramen. A rigid endoscope can be used but would necessitate a second burr hole and trajectory with a more inferior entry point on the forehead. The risks of an endoscopic biopsy are considerable due to the limited tissue sampling and difficulty achieving hemostasis within the ventricle. Even minor bleeding can obscure the operative field, making it difficult to identify the target. In general, given these limitations, a stereotactic biopsy is preferable to endoscopic biopsy in situations in which diagnostic tissue is desired.