Pineal Tumors

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CHAPTER 125 Pineal Tumors

Jeffrey N. Bruce

Historical Perspective

Although pineal tumors were first described in 1717, the earliest attempts at surgery in the pineal region did not occur until 200 years later.¹ Those initial attempts were led by pioneers such as Horsley, Brummer, and Schloffer, whose boldness in the setting of primitive neurosurgical technique predictably did not produce favorable outcomes.² Oppenheim and Krause reported the first successful removal of a tumor from the pineal region in 1913.³ In 1921, Dandy described the transcallosal approach that he used in three patients with pineal tumors after his scholarly development of the technique in dogs.⁴ In 1926, Krause reported modest success without operative mortality in three patients with the infratentorial approach.⁵ These achievements are testament to the skill and innovation of these remarkable individuals whose work was hampered by the lack of microscopes, lighting, instrumentation, and modern anesthesia.

This modest success provoked interest in approaches to the pineal region; however, the difficulty of operating on these deep-seated lesions was apparent from the unacceptably high surgical mortality and morbidity. A more conservative approach was adopted whereby patients had shunts placed to relieve hydrocephalus and received empirical radiation therapy.⁶^–¹³ Surgery was considered only for patients who failed to respond to radiation treatment. This algorithm was especially favored in Japan, where a high preponderance of radiosensitive germinomas are found.¹⁴^–¹⁷ Unfortunately, this strategy of “blind radiation” led to unnecessary and potentially harmful radiation exposure in a large percentage of patients with benign and radiation-resistant tumors.¹⁸^–²⁰ Eventually, clinical management of these patients became more sophisticated and led to an appreciation of the need for individualized therapy based on specific tumor histology.²¹^–³² This philosophic shift coincided with improvements in neuroanesthetic and microsurgical techniques and spurred development of the modern operative approaches. In 1971, Stein ushered in the microsurgical era for pineal region surgery with his successful modification of Krause’s infratentorial approach.³¹ Subsequently, additional supratentorial approaches have been reevaluated and added to the neurosurgeon’s armamentarium.^21,³³^–³⁸

Safe and effective surgical strategies are essential for current clinical management of pineal tumors because securing a histologic diagnosis is fundamental to decision making.^25,^27,^28,³⁹^–⁴⁴ Distinguishing among the many diverse histologic subtypes that can occur in the pineal region has important implications for planning adjuvant therapy regimens, making prognostic determinations, and establishing follow-up strategies.

Anatomy

The pineal gland is an encapsulated structure that occupies a deep position near the geometric center of the brain. The pineal gland is essentially an extra-axial structure, a feature that makes tumors of the pineal gland readily resectable because a surgical plane can often be established between adjacent structures. Surrounding structures include the posterior commissure ventrally, the corpus callosum superiorly, and the habenular commissure dorsally (Fig. 125-1).⁴⁵ The velum interpositum, which incorporates the internal cerebral veins and the choroid plexus, is intimate with the dorsal gland. The basal veins of Rosenthal combine with the internal cerebral veins to form the vein of Galen before draining into the straight sinus. The blood supply to the pineal gland is from branches of the medial and lateral choroidal arteries through anastomoses to the pericallosal, posterior cerebral, superior cerebellar, and quadrigeminal arteries.^46,⁴⁷

FIGURE 125-1 Sagittal (A) and dorsal (B) drawings of pineal region anatomy.

(From McComb J, Levy M, Apuzzo M. The posterior intrahemispheric retrocallosal and transcallosal approaches to the third ventricle region. In: Apuzzo M, ed. Surgery of the Third Ventricle. 2nd ed. Baltimore: Williams & Wilkins; 1998:743-777.)

Most pineal masses originate infratentorially and expand into the posterior third ventricle. Further progression can proceed into the thalamus or posteriorly over the dorsal surface of the quadrigeminal plate. Malignant tumors, particularly of glial origin, can invade into the midbrain and thalamus, which ultimately determines the tumor’s resectability.

Pathology

The different cell types that make up the pineal gland account for the diverse pathology of pineal region tumors. The mature pineal gland is made up of pinealocytes arranged in lobules to form the pineal parenchyma.⁴⁵ The pinealocytes are surrounded by astrocytes, with endothelial cells forming the vasculature and connective tissue cells forming septa between the lobules. The gland also contains nerve endings from sympathetic nervous innervation to the pinealocytes. The ependymal cells of the third ventricle adjoin the gland along its anterior border.

The term pinealoma was originally used by Krabbe but is a misnomer because it initially pertained to germ cell tumors.⁴⁸ Eventually, this term was applied more generically to any tumor of the pineal region, but it is now obsolete. Pineal region tumor is the preferred general term; the individual tumor’s histology is used for specificity (e.g., astrocytoma of the pineal region).⁴⁹

Pineal tumors are grouped into four main categories: germ cell tumors, pineal parenchymal cell tumors, glial cell tumors, and other miscellaneous tumors and cysts.²¹ Within each category, tumors exist along a continuum from benign to malignant; mixed tumors of more than one cell type also occur.^42,^50,⁵¹

The miscellaneous category includes such entities as meningioma, hemangioblastoma, choroid plexus papilloma, metastatic tumor, chemodectoma, adenocarcinoma, and lymphoma.^21,^29,^52,⁵³ Additionally, a variety of vascular lesions can occur, including cavernous malformations, arteriovenous malformations, and vein of Galen malformations.^43,⁵⁴

Benign pineal cysts are being encountered with greater frequency as the indications for radiographic imaging expand (Fig. 125-2).^55,⁵⁶ Histologically, these cysts are benign, normal variants of the pineal gland and consist of cystic structures surrounded by normal pineal parenchymal tissue. They can be up to 2 cm in diameter, with a contrast-enhancing rim representing compressed pineal gland tissue. They are nearly always asymptomatic and generally do not require treatment unless they are causing aqueductal obstruction. Radiographically, pineal cysts can mimic pilocytic astrocytomas, although tumors can be distinguished by their increased tendency to be progressive and symptomatic. The natural history of pineal cysts is that of a static anatomic variant that does not require treatment.

FIGURE 125-2 Gadolinium-enhanced magnetic resonance image of a typical pineal cyst. The cyst has peripheral enhancement and is not causing obstruction of the sylvian aqueduct. These cysts are normal anatomic variants that are rarely symptomatic and seldom require treatment.

Clinical Features

Initial Symptoms

Pineal region tumors are generally manifested in one of three ways ^21,⁵⁶: (1) symptoms of increased intracranial pressure from obstructive hydrocephalus, (2) direct brainstem and cerebellar compression, or (3) endocrine dysfunction.

The most common initial symptom is headache, which is associated with obstructive hydrocephalus secondary to compression of the aqueduct of Sylvius. Further progression of hydrocephalus can lead to nausea, vomiting, obtundation, cognitive impairment, papilledema, and ataxia. In rare cases, symptoms can develop abruptly in association with pineal apoplexy from hemorrhage in a pineal tumor.⁵⁷^–⁶⁰

Direct compression of the midbrain, particularly at the level of the superior colliculus, can cause disorders of extraocular movement, classically known as Parinaud’s syndrome.^61,⁶² This syndrome can consist of paralysis of upgaze, convergence or retraction nystagmus, and light-near pupillary dissociation. The sylvian aqueduct syndrome, which consists of paralysis of downgaze or horizontal gaze from further midbrain compression, can be superimposed on Parinaud’s syndrome.⁶³ Dorsal midbrain compression or infiltration can lead to lid retraction (Collier’s sign) or ptosis. Less commonly, fourth nerve palsies with diplopia and head tilt may occur. Although eye signs can be due to either hydrocephalus or direct brain compression, symptoms from hydrocephalus generally recede after a cerebrospinal fluid (CSF) diversion procedure. Interference with the cerebellar efferent pathways of the superior cerebellar peduncles can cause ataxia and dysmetria. Rare cases of hearing dysfunction have been reported, probably caused by a disturbance in structures associated with the inferior colliculi.^64,⁶⁵

Endocrine dysfunction is rarely encountered but usually arises from the secondary effects of hydrocephalus or from spread of tumor to the hypothalamic region.⁶⁶ Diabetes insipidus can occur with a germinoma spreading along the floor of the third ventricle. Such symptoms may develop early in the disease process, even before the tumor is radiographically apparent. Precocious puberty has been linked historically with pineal masses; however, documented cases are rare.^48,^66,⁶⁷ This syndrome is actually precocious pseudopuberty because the hypothalamic-gonadal axis is not mature, and it is therefore limited to boys whose choriocarcinoma or germinoma contains syncytiotrophoblastic cells producing ectopic secretion of β-human chorionic gonadotropin.^66,⁶⁸

Diagnosis

Magnetic resonance imaging (MRI) with gadolinium enhancement is the principal diagnostic test for pineal tumors.^49,⁶⁹^–⁷¹ MRI reveals the degree of hydrocephalus and allows evaluation of tumor size, vascularity, homogeneity, and anatomic relationships with surrounding structures. In planning the operative approach, knowledge of the relevant anatomic relationships is useful, including the position of the tumor within the third ventricle, the amount of lateral and supratentorial extension, and the degree of brainstem involvement. The extent of tumor invasiveness can be estimated from the margination and irregularities of the tumor border; however, the true degree of tumor encapsulation can be defined only at surgery.⁴²

Pineal tumors generally displace the vessels of the deep venous system superiorly along the dorsal periphery of the tumor. This is an important point when planning surgical approaches because most tumors can be separated from the surrounding veins and midbrain (Fig. 125-3).⁴² Notable exceptions are meningiomas arising from the velum interpositum and epidermoid or other tumors originating in the corpus callosum. These tumors displace the deep venous system ventrally and inferiorly, thereby providing a diagnostic clue on MRI. The position of the tumor relative to the deep venous system is important because it may influence the choice between an infratentorial and a supratentorial approach. Although the location of the deep venous system may be conspicuous on MRI, magnetic resonance venography may be desirable to better delineate it.

FIGURE 125-3 Magnetic resonance images showing the variability of the deep venous system in relation to pineal region tumors. A, The deep venous system is located superior and dorsal to the tumor. This is the most common configuration and is conducive to an infratentorial-supracerebellar approach. B, The deep venous system is located inferior and ventral to this epidermoid tumor and is conducive to a supratentorial approach.

Despite advances in high-resolution MRI, tumor histology cannot be reliably predicted on the basis of imaging features alone.^21,^69,^70,^72,⁷³ Computed tomography can complement MRI by providing details of calcification, blood-brain barrier breakdown, and the degree of vascularity.⁷⁴ Angiography is not necessary unless a vascular anomaly is suspected.

Tumor Markers

The presence of α-fetoprotein or β-human chorionic gonadotropin, measured in either serum or CSF, is pathognomonic for malignant germ cell elements (Table 125-1).^47,^56,⁷⁵ CSF levels tend to be more sensitive than serum levels.^51,^56,⁷⁵ α-Fetoprotein indicates the presence of fetal yolk sac elements, and levels are markedly elevated with endodermal sinus tumors; smaller elevations are seen with some embryonal cell carcinomas and immature teratomas.^56,^68,⁷⁵^–⁷⁹ β-Human chorionic gonadotropin is produced by trophoblastic elements; high levels are found with choriocarcinomas, whereas low levels can be associated with some, but not all embryonal cell carcinomas and germinomas.^49,^56,^68,^75,^76,^78,⁸⁰^–⁸³ Although the presence of germ cell markers indicates a malignant germ cell tumor, the converse is not necessarily true. That is, the absence of germ cell markers should be interpreted cautiously because it does not rule out the presence of a germinoma or embryonal cell carcinoma. Similarly, if α-fetoprotein is elevated in the presence of a germinoma, it is likely that an embryonal cell carcinoma or endodermal sinus tumor is present as part of a mixed tumor.⁸⁴

TABLE 125-1 Biologic Markers in Germ Cell Tumors

TUMOR	β-HUMAN CHORIONIC GONADOTROPIN	α-FETOPROTEIN
Benign germ cell	−	−
Immature teratoma	?	+/−
Germinoma	−	−
Germinoma with syncytiotrophoblastic cells	+	−
Embryonal cell carcinoma	+/−	+/−
Choriocarcinoma	++	−
Endodermal sinus tumor	−	++

Tumor markers are useful for monitoring response to adjuvant therapy or as an early sign of recurrence. Because they are reliable indicators of malignant germ cell elements, the presence of malignant germ cell markers makes surgery and biopsy unnecessary, and such patients should be managed with radiation therapy and chemotherapy. Other biologic markers for germ cell tumors include lactate dehydrogenase isoenzymes and placental alkaline phosphatase.^56,^85,⁸⁶ These germ cell markers have diagnostic value when used for the immunohistochemical analysis of histologic specimens but are not useful as serum or CSF markers.

Markers such as melatonin and S-antigen have been investigated in patients with pineal parenchymal cell tumors.^45,⁸⁷^–⁹⁰ These markers also have more applicability in immunohistochemical diagnosis. Analysis of melatonin levels in postoperative patients has been investigated but has little clinical applicability.

Treatment

Management of Hydrocephalus

Most patients are initially seen with obstructive hydrocephalus, which can be managed in several ways. Symptomatic patients are best managed initially with a stereotactic-guided endoscopic third ventriculostomy to allow gradual reduction of intracranial pressure and resolution of symptoms before tumor resection.⁹¹ This method is preferable to ventriculoperitoneal shunting because it eliminates potential complications such as infection, overshunting, and peritoneal seeding of malignant cells. Mildly symptomatic patients in whom gross total resection is anticipated at surgery can be managed with a ventricular drain placed at the time of surgical resection.^25,⁹² The drain can be removed or converted to a shunt in the postoperative period as circumstances dictate.

Tissue Diagnosis: Biopsy versus Open Resection

Given the diverse pathology that can occur in the pineal region, a histologic diagnosis is necessary to optimize management decisions.^42,^44,⁹²^–⁹⁵ An individual tumor’s histology strongly influences the choice of postoperative adjuvant therapy, need for metastatic work-up, estimation of prognosis, and planning of long-term follow-up. Although CSF cytology and radiographic examination provide insight into the histologic diagnosis, they are not sufficiently sensitive to supplant a tissue diagnosis.^72,⁹⁶^–¹⁰¹ CSF cytology occasionally reveals malignant cells but is rarely diagnostic. The only time that a tissue diagnosis is unnecessary is in the presence of malignant germ cell markers; in these cases, chemotherapy and radiation therapy should proceed without a biopsy.^92,^100,¹⁰²

Tissue diagnosis can be achieved by either stereotactic biopsy or an open procedure. This decision is influenced by the clinical features of the patient, radiographic features of the tumor, and the surgeon’s degree of experience with the procedures. Inflexible or dogmatic dedication to either procedure is not appropriate. In general, patients with known primary systemic tumors, multiple lesions, or medical conditions that make open resection dangerous are good candidates for stereotactic biopsy.^49,⁹² Radiographic evidence of brainstem invasion might make stereotactic biopsy an attractive choice; however, the degree of invasion seen radiographically can be misleading and may not reflect a dissectible tumor capsule at surgery. The advantage of open resection is the ability to obtain larger amounts of tissue and more extensive tissue sampling. This is particularly important for pineal region lesions in general and germ cell tumors in particular because heterogeneity and mixed cell populations are common. This diversity makes it difficult for neuropathologists to appreciate the subtleties of histologic diagnosis when only small specimens are available (Fig. 125-4; Table 125-2).^25,^92,¹⁰³^–¹⁰⁵

FIGURE 125-4 Sagittal magnetic resonance image (A) and gross pathology (B) from a patient with a mixed germ cell tumor demonstrating the heterogeneity of the tumor. Such heterogeneity can lead to misdiagnosis if tissue sampling is limited.

TABLE 125-2 Pure versus Mixed Germ Cell Tumors at the New York Neurological Institute (1978-2000)

TUMOR TYPE	NUMBER
Pure Germ Cell Tumors
Germinoma	30
Teratoma	9
Epidermoid	3
Immature teratoma	2
Embryonal carcinoma	2
Lipoma	2
Total	48
Mixed Germ Cell Tumors
Germinoma/teratoma	4
Germinoma/embryonal carcinoma	3
Immature teratoma/germinoma/EST	2
Germinoma/dermoid	1
Germinoma/immature teratoma	1
Choriocarcinoma/teratoma	1
Choriocarcinoma/immature teratoma	1
Embryonal carcinoma/EST	1
EST/embryonal carcinoma/germinoma	1
Nonspecified mixed	2
Total	17

EST, endodermal sinus tumor.

Additionally, a clinical advantage is gained when the tumor burden is reduced with an open procedure. For the third of tumors that are benign, resection is usually complete and curative, thus making it the clear procedure of choice (Table 125-3).^42,^92,¹⁰⁶ The advantages of tumor debulking are less apparent with malignant tumors; however, anecdotal evidence favors more radical resection, when possible, to improve the response to adjuvant therapy.^34,^92,¹⁰⁶^–¹⁰⁸ Additionally, for certain patients with mild hydrocephalus whose tumors can be completely resected, shunting can be avoided.^25,⁹²

TABLE 125-3 Extent of Resection for 128 Consecutive Pineal Region Surgeries at the New York Neurological Institute (1990-2008)

Stereotactic biopsy offers the advantages of relative ease of performance and reduced complications when compared with an open procedure.^24,^29,¹⁰⁹^–¹¹¹ Usually, only local anesthesia is necessary. However, stereotactic biopsy carries a risk for hemorrhage from several mechanisms, including bleeding in highly vascular tumors, damage to the deep venous system, and bleeding into the ventricle, where tissue turgor is insufficient to tamponade minor bleeding.^25,^92,^103,^110,¹¹² These risks notwithstanding, several large series have validated the relative safety of stereotactic biopsy for these tumors despite their rather hazardous location.^24,¹⁰⁹ Of minor concern but worth mentioning is a report of metastatic seeding along the biopsy tract after biopsy of a pineoblastoma.¹¹³

Surgical Techniques

Stereotactic Procedures

The relative technical ease of performing stereotactic biopsy procedures should be viewed cautiously with regard to lesions in the pineal region. There are numerous pitfalls that must be avoided to complete a successful biopsy. An appreciation of the complex anatomy at the biopsy site and through the potential trajectory is critical.

Most target-centered stereotactic frame systems are adequate for biopsy. Computed tomography is sufficient to provide accurate targeting information and to track the trajectory in three dimensions. MRI provides more sensitive soft tissue visualization, and current software has minimized any spatial inaccuracy. Volumetric treatment planning should be used to identify the trajectory in all the axial, sagittal, and coronal planes. Two possible approaches are favored for stereotactic surgical trajectories.^24,^29,^56,¹¹⁴ The most common is through a precoronal entry point, with the tumor being reached through an anterolaterosuperior approach that avoids the interior surface of the lateral ventricle and comes inferior and lateral to the internal cerebral veins to reduce the risk for bleeding. The alternative approach is through a posterolaterosuperior approach near the parieto-occipital junction, which can be useful for tumors that extend laterally or superiorly.

Serial biopsies are desirable whenever possible; however, this is often prohibited by the small size of the tumors commonly encountered.^24,¹⁰⁹ The side-cutting cannula type of biopsy needle is preferred over a cup forceps instrument, which can tear a blood vessel. If bleeding is encountered, continuous suction and irrigation for up to 15 minutes may be necessary. When bleeding is suspected, an immediate scan should be obtained to assess for intraventricular blood and the degree of hydrocephalus to determine the need for ventricular drainage.

Endoscopic Biopsy

Endoscopic biopsy of pineal tumors through the ventricles has been reported as an alternative method for securing a tissue diagnosis.¹¹⁵^–¹¹⁹ In addition to sampling error, a major drawback of this procedure is that the tumor is biopsied along its ventricular surface, where there is no tissue turgor to tamponade the bleeding. Even minor bleeding within the CSF space can be difficult to manage, a problem that is compounded by the highly vascular properties of many pineal tumors. Typically, this procedure is combined with a ventriculostomy. However, even with flexible endoscopes, it is difficult to perform a biopsy simultaneously with a ventriculostomy because the trajectory required is different for each procedure. The rigid endoscope is not easily maneuverable without risk of damage to the fornix and the septal and thalamostriate veins at the foramen of Monro. A suitable entry point through the forehead might allow the use of a rigid scope, but this offers no advantage over a simple stereotactic biopsy. More typically, endoscopes have been used to aspirate pineal cysts; however, the benefits of this approach are equivocal.

Operative Procedures

Several variations on approaches to the pineal region exist, but essentially they are categorized as supratentorial or infratentorial.^36,^42,⁹² Supratentorial approaches include transcallosal interhemispheric, occipital transtentorial, and the rarely used transcortical transventricular.^13,^34,^92,¹²⁰ The infratentorial approach is through a natural corridor created between the tentorium and the cerebellum.^31,¹²¹ The choice of approach depends on the surgeon’s experience and comfort with the specific technique. Many of these approaches are interchangeable, although there are several caveats. Large tumors that extend supratentorially or laterally to the trigone of the lateral ventricle generally benefit from a supratentorial approach.⁹² Supratentorial approaches afford greater exposure than infratentorial approaches do, but they have the disadvantage of forcing the surgeon to work around the convergence of the vein of Galen and internal cerebral veins, where they interfere with tumor removal.

The location of most pineal tumors infratentorially and in the midline gives the infratentorial supracerebellar approach several natural advantages.^92,¹²² It is performed with the patient in the sitting position, whereby gravity allows the cerebellum and the tumor to drop downward. The tumor can then be dissected more easily off the deep venous system and velum interpositum, which is often the most technically difficult portion of tumor dissection. Besides the obvious anatomic advantage of using a midline trajectory, the deep venous system lies dorsal to the mass, thus making it more avoidable through most of the tumor dissection. The approach is less favorable if the tumor has a significant supratentorial or lateral extension, although with appropriate extra-long instruments, even tumors extending anteriorly into the third ventricle can be removed.

Patient Positioning

Numerous patient positions have been described for these approaches, each having advantages and disadvantages (Fig. 125-5).

FIGURE 125-5 Patient positions for approaches to the pineal region. A, Sitting position. B, Three-quarter prone position. C, Prone position. D, Concorde position.

(A-C, From Bruce J. Posterior third ventricular tumors. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:769-775; D, from Bruce J, Stein B. Supracerebellar infratentorial approach. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:815-824.)

Sitting Position

The sitting position is usually preferred for the infratentorial supracerebellar approach (see Fig. 125-5A).^92,¹²² Gravity works in the surgeon’s favor by reducing pooling of blood in the operative field and by facilitating dissection of the tumor from the deep venous system. The risks for air embolism, pneumocephalus, or subdural hematoma associated with cortical collapse can be anticipated and managed with proper precautions.^92,¹²³ Doppler monitoring helps detect small amounts of air entering the venous system during the operative procedure. A central venous catheter can be used to remove entrapped air if necessary.

The patient is brought to the sitting position by manipulating the operative table from the supine position while an assistant stabilizes the patient’s head. A reverse table capable of being lowered close to the floor is desirable. The head is flexed so that the tentorium is approximately parallel to the floor. The patient’s legs should be elevated to assist venous return. A three-point vise type of head holder keeps the head immobile. At least two fingerbreadths of space is needed between the patient’s chin and sternum to avoid compromising the airway and venous return. A Greenberg self-retaining retractor or similar system is arranged to frame the operative field to assist in cerebellar retraction and serve as a holder for cottonoids.

Lateral Position

The lateral decubitus position with the dependent, nondominant right hemisphere down is generally used.¹²⁴ The head is raised approximately 30 degrees above the horizontal in the midsagittal plane, especially for the transcallosal approach. For the occipital transtentorial approach, the head should be positioned with the patient’s nose rotated 30 degrees toward the floor.

A more desirable variation of this approach is the three-quarter prone position (Fig. 125-5B).¹²⁵ The legs are flexed with a pillow between them, and the patient is strapped down so that the table can be rotated during the procedure to improve exposure when appropriate. The three-quarter prone position is essentially an extension of the lateral position, except that the head is at an oblique 45-degree angle with the nondominant hemisphere dependent. This is suitable for more posterior approaches, such as the occipital transtentorial as opposed to the transcallosal approach. The nondominant hemisphere is easily retracted with the help of gravity. Surgeon fatigue is reduced because the surgeon’s hands are on a horizontal plane and are not extended to the degree they are with patients in the sitting position. The three-quarter prone position can be cumbersome and requires placing an axillary roll under the patient’s right axilla with the right arm supported in a sling-like fashion beneath the patient. A supporting roll is placed under the left thorax, and a three-point head-pin vise holder is used to support the head in a slightly extended and rotated position to the left at a 45-degree oblique angle. The patient is securely strapped, and the legs and feet are elevated to facilitate venous return.

Prone Position

The prone position is simple and safe for supratentorial approaches (Fig. 125-5C).^92,¹²⁰ It is generally comfortable for the surgeon, although the operative field is considerably raised, which makes it difficult for the surgeon to be seated. This position is useful when two surgeons work together through an operative microscope that has a bridge to allow simultaneous binocular vision. The steep angle of the tentorium, however, makes the prone position impractical for the infratentorial approach. This position is often useful in the pediatric population. To facilitate its use, the position of the head can be rotated 15 degrees away from the craniotomy side in a variation known as the Concorde position (Fig. 125-5D).¹²⁶

Operative Approaches

Infratentorial Supracerebellar Approach

The infratentorial supracerebellar approach was first described by Krause at the beginning of the 20th century (Fig. 125-6, Video 125-1).⁵ The technique was lost for many years because of limitations in microsurgical technique until its rediscovery in 1971 by Stein.³¹

FIGURE 125-6 Infratentorial supracerebellar approach. A, Sagittal diagram showing the initial trajectory (A) in line with the vein of Galen. After opening the arachnoid over the quadrigeminal plate, the trajectory should be adjusted several degrees downward in line with the center of the tumor (B) to avoid damage to the deep venous system. B, Operative photograph demonstrating the exposed dorsal surface of the tumor after opening the arachnoid and dividing the precentral cerebellar vein. C, Diagram of the tumor exposure seen in B. D, Operative photograph with a view into the third ventricle after excision of the tumor. E, Diagram of the tumor bed seen in D.

(From Bruce J, Stein B. Supracerebellar infratentorial approach. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:815-824.)

The infratentorial supracerebellar approach is usually performed with the patient in the sitting position.^42,^92,¹²² If necessary, a ventricular drain can be placed in the trigone of the lateral ventricle through a bur hole in the midpupillary line at the lambdoid suture. A suboccipital exposure is begun through a linear midline incision extending from just above the torcular and external occipital protuberance down to the level of the C4 spinous process. The incision is brought through the nuchal ligament of the suboccipital musculature. It is not necessary to detach the muscles from the spinous processes of C1 and C2, and the foramen magnum does not need to be exposed. A single low-profile, self-retaining retractor is used to retract the muscles and fascia of the suboccipital region for exposure of the suboccipital bone. The craniotomy is centered just below the torcular. The bony opening must be sufficient to provide access for the surgical instruments and adequate light from the operating microscope. A craniotomy is preferred over a craniectomy because it reduces the incidence of postoperative aseptic meningitis, fluid collections, and discomfort. Slots are drilled over the sagittal sinus, above the torcular, and over both lateral sinuses. A final slot is drilled approximately 1 or 2 cm above the foramen magnum in the midline. A craniotome is used to connect the slots, which allows the bone flap to be elevated. Sufficient bone should be removed above the transverse sinus to ensure that the view along the tentorium is not obscured. Any bone edges should be carefully waxed, and all venous bleeding should be controlled to avoid air emboli.

The dura is opened in a gentle semilunar curve that extends from the lateral aspects of the exposure. The dural flap is reflected upward and placed on slight tension with tenting sutures and rubber bands. Excess retraction obstructs the sinuses and should be avoided. The inferior dura acts as a sling to support the cerebellar hemispheres. If the posterior fossa is tight, fluid can be removed from a ventricular drain or by opening the cisterna magna.

To open the infratentorial corridor, the arachnoidal adhesions and midline bridging veins between the dorsal surface of the cerebellum and the tentorium are cauterized and carefully divided. The presence of extensive collateral circulation minimizes complications from venous sacrifice; however, to minimize risk, it is desirable to preserve any veins found laterally.¹²⁷ Cauterizing the bridging veins and dividing them midway can minimize the nuisance of bleeding from the sinus. When these attachments are divided, the cerebellum drops away from the tentorium to provide an excellent corridor with minimal brain retraction. The dorsal surface of the cerebellum can be protected with padding such as Telfa, and a small brain retractor can be used to provide additional cerebellar retraction in a posterior and inferior direction. Additional adhesions and bridging veins can be divided when they become visible near the anterior vermis as the cerebellum is retracted. With the retractor in place, the opalescent arachnoid covering the pineal region can be seen.

The operating microscope is brought in at this time. Because of the range of angles and different depths encountered along the operative trajectory, a microscope with a variable objective is desirable to facilitate the use of long instruments. Inclined eyepieces with a wide degree of rotation accommodate the different operative angles. A freestanding armrest assists the surgeon and prevents fatigue.

Under the microscope, the arachnoid overlying the quadrigeminal plate is sharply opened. This is generally an avascular plane, and minimal cautery is necessary. The precentral cerebellar vein is identified as it courses from the anterior vermis to the vein of Galen and should be carefully dissected, cauterized, and divided. Although this vein can be taken without difficulty, it is not advisable to cauterize any other veins of the deep venous system. The retractor can then be adjusted to visualize the inferior portion of the tumor. The trajectory of the microscope is adjusted downward along the central axis of the tumor away from the initial plane parallel to the tentorium, where it would otherwise lead to direct encounter with the vein of Galen (see Fig. 125-6A).

With the posterior surface of the tumor exposed, the central portion is cauterized and opened with a long-handled knife or bayonet scissors (Fig. 125-6B and C). Specimens can be taken from within the capsule and sent for frozen diagnosis. The accuracy of frozen tissue diagnosis is low, however, and this should be taken into consideration during intraoperative decision making. The tumor is then internally debulked with a variety of instruments such as suction, cautery, tumor forceps, and a Cavitron ultrasonic aspirator if necessary. Most tumors are soft and can generally be suctioned with a large-bore Japanese-style suction device with variable control. As the tumor is decompressed, the capsule can be separated from the surrounding thalamus. Most of the vessels along the wall of the capsule are choroidal vessels and need not be preserved. The dissection continues until the third ventricle is encountered. The tumor is then carefully dissected inferiorly off the brainstem. This is often the most difficult portion of the tumor dissection and can be facilitated by retracting the tumor superiorly and dissecting it bluntly off the brainstem under direct vision. Finally, the tumor is removed superiorly after separating the attachments along the velum interpositum and the deep venous system. These attachments can be carefully cauterized and sharply dissected, although a rent in the deep venous system can be difficult to control and must be avoided.

Intraoperative decision making regarding the extent of tumor resection depends on the degree of tumor invasion. Some tumors directly invade the brainstem, and the degree of resection is a matter of judgment. Although there is evidence that more radical resection of even malignant tumors improves the efficacy of adjuvant therapy and reduces the risk for postoperative hemorrhage, this is still a matter of judgment.

Once tumor removal is completed, the surgeon should have a comprehensive view into the third ventricle (Fig. 125-6D and E). Flexible mirrors can be useful for examining the inferior portion of the tumor bed to verify the extent of resection and to avoid leaving any blood clots. Careful attention must be given to hemostasis.^92,¹²⁸ Generally, direct but careful cautery is preferable. It is advisable to avoid extensive use of hemostatic agents, which can float into the ventricle and obstruct a shunt or the aqueduct. If absolutely necessary, long strips of Surgicel draped over the surface of the cerebellum and covering the tumor bed can provide hemostasis with small risk of floating into the ventricle.

Once hemostasis is obtained and the retractors are removed, the dura is closed in as watertight a manner as possible. The bone flap is plated into place to reduce postoperative pain and inflammation. The patient should be extubated with a reasonable degree of head elevation to avoid shifting the decompressed brain within the cranial vault.

Transcallosal Interhemispheric Approach

The transcallosal interhemispheric approach was first described by Dandy (Fig. 125-7).^8,⁴⁴ This approach between the falx and hemisphere of the brain involves a corridor along the parieto-occipital junction. Dandy’s early contributions recognized the importance of the deep venous system and the cortical bridging veins between the hemisphere and the sinus. Any of the previously described patient positions can be used for this approach, although the prone or sitting position is generally preferred.

FIGURE 125-7 Transcallosal interhemispheric approach. A, Opening of the corpus callosum. B, Magnified view of the opening into the corpus callosum. The falx and tentorium may be divided for further exposure. C, Operative photograph demonstrating tumor exposure and the internal cerebral vein overlying the tumor.

(A and C, from Bruce J. Posterior third ventricular tumors. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:769-775; B, from Rosenfeld J. Supratentorial approaches to pineal tumors. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:825-840.)

Positioning of the bone flap depends on where the tumor is centered in the third ventricle.^120,^129,¹³⁰ A wide craniotomy roughly 8 cm in length provides flexibility in determining the corridor and avoiding bridging veins whenever possible. The craniotomy is generally centered over the vertex to avoid manipulation of the occipital lobe. A U-shaped scalp flap extending across the midline and reflected laterally provides adequate exposure. A bur hole is made over the sagittal sinus, both anteriorly and posteriorly, and a craniotome is used to turn a generous craniotomy. The craniotomy should extend 1 to 2 cm to the left of the sagittal sinus. Bleeding from the sagittal sinus can be controlled with hemostatic agents.

The dura is opened in U-shaped fashion and reflected medially toward the sagittal sinus. The bridging veins are inspected, and an approach is chosen that will minimize the number of veins sacrificed. It is unlikely that sufficient exposure can be achieved without sacrificing at least one bridging vein, although sacrifice of more than one should be avoided if possible. Because these tumors are deeply seated, even a small opening provides a wide angle of deep exposure. The exposed hemisphere is covered with Bicol or Telfa, and a retractor system, such as the Greenberg retractor, is used to frame the opening and provide two retractors to draw the parietal lobe back in a gentle arc. A separate retractor can be used along the falx, which may be divided inferiorly to provide further retraction. This is generally a nonvascular corridor with few adhesions between the falx and the cingulate gyrus.

The corpus callosum is easily identified with the operating microscope by its striking white appearance. The pericallosal arteries are identified as a paired structure running over the corpus callosum. These arteries are retracted either to one side or with separate retractors to each side. The opening into the corpus callosum, centered over the maximal bulge of the tumor, is generally about 2 cm, which is not likely to lead to disconnection syndrome or cognitive impairment (see Fig. 125-7A). Even more posterior openings in the splenium have been performed routinely without deficits. The corpus callosum is generally thin and can be opened with gentle suction and cautery. The lateral extent of the opening is determined by the amount that is sufficient to expose the tumor and avoid damage to the pericallosal arteries. If necessary, the tentorium and falx can be divided to provide additional exposure (Fig. 125-7B).

Once through the corpus callosum, the dorsal surface of the tumor can be seen, and the veins of the deep venous system must be identified early to prevent damage to them (Fig. 125-7C). The importance of the deep venous system and the degree of venous collaterals is a topic of anecdotal speculation. Obviously, sacrificing any vein is undesirable. Whether one vein can be sacrificed safely is questionable, but certainly interruption of two would have a devastating result.

Once the tumor is exposed, it is debulked and then dissected as described previously. Leaving a ventricular drain in place for 1 or 2 days is optional.

Occipital Transtentorial Approach

The occipital transtentorial approach, originally described by Horrax and later modified by Poppen, is a variation of the supratentorial approaches (Fig. 125-8, Video 125-2).^35,¹³¹ A three-quarter prone position is generally preferred. This approach to the pineal region uses an oblique trajectory for lesions that are essentially midline and may therefore be disorienting to surgeons who are not familiar with it. However, by dividing the tentorium, excellent exposure of the quadrigeminal plate is achieved, thus making it particularly useful for tumors that extend inferiorly.

FIGURE 125-8 Occipital transtentorial approach. A, Exposure of the pineal region can be expanded by dividing the tentorium and the falx. B, Exposure of the tumor after dividing the tentorium. C, Operative photo demonstrating tumor after the tentorium is divided. D, Operative photo after tumor removal.

(From Rosenfeld J. Supratentorial approaches to pineal tumors. In: Kaye A, Black P, eds. Operative Neurosurgery. Vol 1. London: Churchill Livingstone; 2000:825-840.)

A U-shaped right occipital scalp flap is reflected inferiorly, with the medial vertical limb beginning just to the left of midline at about the level of the torcular.^34,¹²⁹ A bur hole is placed in the midline over the sagittal sinus just above the torcular, along with another bur hole 6 to 10 cm above this. A craniotome is then used to turn a generous craniotomy extending 1 to 2 cm left of midline. Alternatively, it is feasible to place the bur holes adjacent to the sagittal sinus without crossing the midline. If this option is chosen, it is important to get as close as possible to the sagittal sinus to avoid a bony overhang that limits the operative view.

With the three-quarter prone position, gravity helps with retraction of the nondominant occipital lobe, which is also facilitated by the lack of bridging veins near the occipital pole. Mannitol and ventricular drainage are useful for relaxing the brain and minimizing the risk for hemianopia from excessive occipital lobe retraction.

Under the operating microscope, the straight sinus is identified so that the tentorium can be divided adjacent to it (Fig. 125-8A). A retractor can be placed over the falx for exposure. The inferior sagittal sinus and falx can be divided to facilitate further falcine retraction. At this point, the arachnoid overlying the tumor and the quadrigeminal cisterns can be seen (Fig. 125-8B). Tumor removal proceeds as described earlier while taking care to avoid injury to the deep venous system. Closure and hemostasis proceed as described previously.

Transcortical Transventricular Approach

The transcortical transventricular approach was developed by Van Wagenen, who used a trajectory through the right lateral ventricle via a transcortical incision.¹³ This approach is rarely used because the exposure is limited and the need for a cortical incision is undesirable. Obviously, an entry point should be chosen in noneloquent cortex. Stereotactic guidance is often useful with this approach and may be desirable for a tumor that extends into the lateral ventricle.

Postoperative Care

High-dose steroids should be maintained for the first few days and then tapered as the patient’s condition improves.^128,¹²⁹ Lethargy and mild cognitive impairment are common and make it difficult to evaluate neurological status in the immediate postoperative period, particularly in patients with extensive subdural air as a result of the sitting position. Careful and frequent neurological examinations are necessary, and any changes should be investigated by computed tomography to rule out the possibility of hydrocephalus, hemorrhage, or residual air. Shunt malfunction is a frequent immediate problem caused by air, blood, or operative debris; it is particularly worrisome because deterioration and major morbidity can occur rapidly.

Patients should be encouraged to mobilize and ambulate as early as possible in the postoperative period. With ataxic patients, physical therapy and rehabilitation consultation are important to support rapid mobilization.

If a drain was placed at the time of surgery, it should be removed or converted to a shunt within the first 72 hours to minimize the risk for infection. Postoperative MRI with gadolinium enhancement should be performed within 72 hours to determine the extent of resection and guide future management decisions.

Complications

Patients frequently have some impairment in extraocular movements in the immediate postoperative period, particularly limited upgaze and convergence.^38,^106,¹²⁸ Some degree of pupillary impairment with difficulty focusing may also occur. Many of these extraocular problems are transient and resolve within the first few days, although they can persist for several months. Permanent major impairment is rare, but some mild limitation of upgaze is not unusual and has little clinical significance. As with most neurological deficits, their persistence and magnitude are proportional to the degree to which they were present preoperatively.^128,¹³² Similarly, ataxia is frequently present but resolves within a few days after surgery.

More severe morbidity is rare but can be a sequela of overzealous brainstem manipulation. This can lead to cognitive impairment or, in its extreme form, even to akinetic mutism. Complications are more common in previously irradiated patients, patients with invasive tumors, and those who were progressively symptomatic preoperatively.^128,¹³²

One of the most devastating complications is hemorrhage into an incompletely resected tumor bed. Patients with highly vascular, invasive tumors such as malignant pineal parenchymal tumors are at greatest risk for this complication.^24,^58,^112,¹²⁸ Small hemorrhages can be managed conservatively, but a large hemorrhage may require immediate evacuation. Such decisions must consider the possibility of obstructive hydrocephalus.

Complications of supratentorial approaches include hemiparesis from brain retraction or from sacrifice of bridging veins.^123,^128,¹³³ Fortunately, these deficits usually resolve spontaneously, and infarction and permanent deficits are rare. Seizure prophylaxis is desirable in the immediate postoperative period, although long-term use is not necessary. Parietal lobe retraction can cause sensory or stereognostic deficits on the opposite side.¹²⁹ Occipital lobe retraction during the transtentorial approach can cause visual field defects.^34,^129,¹³⁴ Although disconnection syndromes have been reported with corpus callosum incisions, this has been rare in our experience, even when the splenium is divided.^120,¹²⁹

Complications related to the sitting position include subdural hematoma, hygroma, and ventricular collapse.^42,^106,¹²³ These conditions are generally self-limited. Air embolism is rarely a problem but can be anticipated by a drop in end-tidal carbon dioxide levels or with Doppler monitoring.

Pineal tumor patients are generally young and have relatively few medical problems. Consequently, the incidence of medical complications such as cardiac or respiratory problems is low.

Surgical Outcome

Surgery in the pineal region is among the most arduous of microsurgical challenges, and outcomes vary substantially with the expertise of individual surgeons. With modern microsurgical techniques, surgical series that include more than 20 patients report operative mortality in 0% to 8% and permanent morbidity in 0% to 12% of patients (Table 125-4).^25,^44,^92,^106,¹³⁵ The impact of surgery on long-term outcome depends on the tumor’s histology and responsiveness to adjuvant therapy. With benign tumors, such as teratomas, cystic pilocytic astrocytomas, dermoid tumors, epidermoid tumors, and low-grade pineocytomas, expectations include complete surgical removal, excellent long-term follow-up, and probable cure.^42,^92,^121,¹³⁶^–¹³⁸

TABLE 125-4 Results of Pineal Region Surgery at the New York Neurological Institute (1990-2008)

Total Procedures	128
Benign pathology	55 (43%)
Malignant pathology	73 (57%)
Diagnosis established	127 (99%)
Surgical Morbidity
Death (pulmonary embolism/cerebellar infarct)	2 (2%)
Permanent major morbidity	1 (1%)
Transient major morbidity (with recovery)	7 (5%)

With malignant tumors, the paucity of surgical series reported in the literature makes it difficult to draw conclusions regarding the effect of the degree of resection on outcome. The anecdotal evidence, however, is that except for germinomas, greater resection improves the prognosis and response to adjuvant therapy.^42,^51,^92,^107,¹³² A small subset of pineocytomas, representing approximately 16% of all pineal cell tumors, are discrete, encapsulated, histologically benign. and fully resectable (Fig. 125-9).^8,^92,^112,^134,^136,¹³⁷ Surgery alone may lead to long-term recurrence-free periods without any additional therapy. Such patients, however, should be monitored closely with serial MRI.

FIGURE 125-9 Magnetic resonance images before (A) and after (B) resection of a well-differentiated pineocytoma. Well-encapsulated tumors that can be completely resected may not require adjuvant therapy.

Postoperative Work-Up

Postoperative MRI with gadolinium enhancement should be performed within 72 hours of surgery to determine the completeness of resection.²¹ Tumor markers, if present preoperatively, should be measured in the postoperative period to serve as a baseline for detecting early recurrence or for monitoring response to treatment.

Spinal MRI to look for spinal seeding is required for patients with pineal cell tumors, malignant germ cell tumors, and ependymomas (Fig. 125-10).^21,^92,^139,¹⁴⁰ MRI of the spine can be difficult to interpret in the immediate postoperative period because blood clots or operative debris can sometimes mimic spinal metastasis. If the images are equivocal, serial images should be obtained before instituting spinal irradiation. CSF cytology should be evaluated by lumbar puncture postoperatively, although this has not been particularly helpful in predicting the metastatic potential of these tumors.^9,^17,^78,^92,^141,¹⁴² Overall, the incidence of spinal seeding is low, and prophylactic spinal irradiation is not recommended unless there is clear radiographic evidence of metastasis.^25,^39,^68,^92,^101,¹⁴³^–¹⁴⁶ The one possible exception is in patients with highly malignant pineoblastomas.^92,^106,¹⁴⁷

FIGURE 125-10 Magnetic resonance image showing drop metastases in a patient with a malignant germ cell tumor.

Adjuvant Therapy

Radiation Therapy

Patients with malignant germ cell or pineal cell tumors require radiation therapy. The recommended radiation dose is 5500 cGy given in 180-cGy daily fractions, with 4000 cGy to the ventricular system and an additional 1500 cGy to the tumor bed.^49,⁹² Recent studies suggest that using a more limited field of irradiation that avoids the adverse side effects of ventricular exposure may be sufficient; however, these studies lack long-term follow-up.¹⁴³

Radiation therapy may be withheld for the rare, histologically benign pineocytoma or ependymoma that has been completely resected.^42,^92,^106,¹³⁷ Identification of this exception is based on intraoperative observation of a well-circumscribed tumor that is well differentiated histologically. Surgical resection alone provides excellent long-term control in these circumstances, but careful follow-up is necessary so that radiation therapy can be contemplated at the first sign of recurrence.

Germinomas are the most radiosensitive malignant tumors in the central nervous system. Some studies report a 90% long-term control rate for these tumors.^93,^146,¹⁴⁸ Among series with more long-term follow-up, 5-year survival rates greater than 75% and 10-year survival rates of 69% have been reported with radiation doses of 5000 cGy.^62,^149,¹⁵⁰ With less than 5000 cGy, a higher incidence of local failure can be expected.^100,¹⁵⁰ Germinomas associated with elevated β-human chorionic gonadotropin levels may have a less favorable prognosis.^151,¹⁵²

Methods of reducing radiation doses are being investigated to avoid the associated long-term side effects. These methods include treatment strategies that combine radiation therapy with chemotherapy.^15,^95,¹⁵³^–¹⁵⁶ Cognitive deficits, hypothalamic and endocrine dysfunction, cerebral necrosis, and de novo tumor formation are some of the reported delayed complications of cranial radiation therapy.^18,^20,^25,¹⁵⁷^–¹⁵⁹ This has particular significance for patients with pineal region tumors because the excellent long-term survival after radiation therapy means that they are likely to live long enough to manifest long-term side effects. Pediatric patients are particularly vulnerable to adverse radiation effects.^68,¹⁶⁰^–¹⁶³

Prophylactic spinal irradiation is controversial in the setting of pineal region tumors. Previously, complete cranial-spinal irradiation was recommended for all malignant pineal tumors; however, the current trend is to avoid spinal irradiation unless there is documented evidence of spinal seeding.* Overall, the incidence of spinal seeding is relatively low, and it is not clear that spinal irradiation prevents metastasis to the spine when no tumor is present on postoperative staging. When seeding has been documented, a dose of 3500 cGy is recommended for the spine.

Chemotherapy

Chemotherapy has been most beneficial in patients with nongerminomatous malignant germ cell tumors; significant improvement in long-term follow-up has been demonstrated with current regimens. Patients with germinomas containing syncytiotrophoblastic giant cells have a less favorable prognosis and may benefit from more aggressive treatment with chemotherapy in addition to radiotherapy.^42,^92,¹⁶⁶

Most of the germ cell chemotherapy regimens have been extrapolated from experience treating germ cell tumors of extracranial origin, where success has been remarkable.¹⁶⁷^–¹⁷⁰ Unfortunately, these regimens have not been as successful in treating intracranial tumors.^16,^25,^40,^68,^80,^152,¹⁷¹^–¹⁷⁴ Most successful chemotherapy regimens are derived from protocols for testicular cancer that use the Einhorn regimen of cisplatin, vinblastine, and bleomycin, although other combinations involving cyclophosphamide or etoposide have been investigated.^95,^172,¹⁷⁵ Recent studies using VP-16 (etoposide) in place of vinblastine and bleomycin to avoid pulmonary toxicity have shown improved response rates with less morbidity.^152,^171,¹⁷³ Currently, a regimen of cisplatin or carboplatin with etoposide is among the most widely used.

The role of radiation therapy combined with chemotherapy in these tumors is unclear.¹⁷⁶ Even though radiation therapy is generally given before chemotherapy, the optimal timing has not been defined. An aggressive approach seems reasonable given the poor prognosis of patients with these tumors. Whether radiation therapy improves survival over chemotherapy alone is not clear, although several reports show increased survival in patients aggressively treated with a combination of chemotherapy, radiation therapy, and surgery.^16,^49,^68,^77,^95,¹⁷⁷^–¹⁸⁰ Delayed surgery after radiation therapy and chemotherapy is indicated for patients with residual tumors whose germ cell markers have normalized.^181,¹⁸² The residual tumor is likely to be benign germ cell elements that are resistant to radiotherapy and chemotherapy. For pure germinomas, the exquisite radiosensitivity of these tumors has made chemotherapy less compelling, except for patients with recurring or metastatic disease. This success has spurred interest in the use of chemotherapy as a means of reducing the overall dosage of radiation.^15,¹⁵³^–¹⁵⁶ ^,183 Although this is a sound philosophy, the long-term results have not withstood the same test of time that radiation therapy alone has for these tumors.

Chemotherapy has been used mostly for recurrent or disseminated pineal cell tumors.^40,^56,^147,¹⁸⁴ There have been some positive responses with various combinations of vincristine, lomustine, cisplatin, etoposide, cyclophosphamide, actinomycin D, and methotrexate. Success with these various regimens has been limited, however, so no clear-cut recommendations can be given.¹³⁹

Radiosurgery

One of the more recent developments in the treatment of pineal region tumors is the application of radiosurgical techniques.^22,^24,^185,¹⁸⁶ Several studies have clearly documented the relative safety of this method, although long-term follow-up results are currently lacking. The problem with radiosurgery is not the response of the targeted mass, but recurrence of tumor outside the treatment volume. Radiosurgery is generally limited to tumors smaller than 3 cm in diameter.

The distinct differences in the radiobiologic effects of radiosurgery and conventional fractionated radiation therapy must be considered when choosing optimal therapeutic strategies. Germinomas, for example, have an excellent long-term response to fractionated radiation, and it is unlikely that radiosurgery can improve on these results. Additionally, because radiosurgery provides no therapeutic coverage of the ventricular system, tumors such as pineal cell and germ cell tumors are particularly vulnerable to ventricular recurrence. Radiosurgery may have its greatest benefit in providing a local boost to the tumor bed so that exposure of the ventricles and surrounding brain to radiation can be reduced.^22,¹⁸⁷ It may also be useful for tumors that recur locally.