History

Walter Dandy was the first to undertake a scholarly analysis of surgery in the pineal region. His supratentorial parafaIcine approach to the pineal region was the culmination of extensive studies first performed on animals. The exact head position that he used is unclear from his writings, but it seems that some operations were done in a semi-sitting position while others were done with the hemisphere on the side of the approach uppermost, retracted against gravity. Once the pineal region was reached, he sectioned the corpus callosum and dissected the deep venous system, which unfortunately often resulted in venous damage and central brain edema. Without an operating microscope, steroids, and sophisticated anesthesia the surgical mortality rate was prohibitively high. Other, just as illustrious, neurosurgeons of that era dismissed the feasibility of operative intervention for pineal tumors because of the technical difficulties encountered and the probability that most of these tumors could not be removed totally because of their malignant and invasive characteristics.

It is remarkable that before Dandy's numerous efforts to surgically treat pineal tumors. Krause (1926) operated on three patients with lesions in the area of the pineal gland which were probably astrocytomas (perhaps one was a teratoma). He had no operative mortality and the operations were done through the posterior fossa over the cerebellum. Considering the limited instrumentation, lack of microscope or good lighting and suboptimal anesthesia, these were operative triumphs.

Since that time a number of different approaches have been advocated, including those around the occipital lobe and over the tentorium as described by Poppen. The approach through a dilated lateral ventricle proposed by Van Wagenen was difficult and never gained wide acceptance. The continued difficulty in achieving successful surgical results led to a more conservative approach for pineal region tumors consisting of the insertion of a shunt for hydrocephalus and radiotherapy for presumed malignancy. Unfortunately, this resulted in numerous articles containing anecdotal information and an excellent opportunity was lost to study the natural history of the wide variety of tumor types in the pineal region.

In the 1970s, the increasing use of the operating microscope rekindled interest in direct surgical approaches to the pineal region. Both Japanese and American neurosurgeons were active in this and there was considerable debate as to the best surgical route to the pineal region. The more important issue, however, was not the route but the fact that these debates stimulated interest in operating on such tumors to identify their nature and remove them whenever possible. The most recent development has been the use of stereotactic biopsy as another option for obtaining tissue for histologic diagnosis.

Because of these more aggressive approaches to pineal region tumors, several principles became evident that are now used to guide the management of pineal region tumors. It is now known that pineal tumor types exist along an extensive continuum of histologic variance from benign to highly malignant. Some of these tumors are mixed in nature, simultaneously containing benign as well as malignant elements or even glial and pineal cell constituents. The diagnosis from small specimens is often difficult, even for an experienced pathologist. Despite the advances in radiographic imaging and increased experience with tumor markers, these preoperative diagnostic tests are insufficient and accurate determination of histologic typing requires operative intervention.

Patient Selection

Surgery is indicated for all patients with symptomatic pineal region masses or patients who are asymptomatic but have aqueductal compromise and hydrocephalus. This is based on the assumption that the histologic diagnosis cannot be made without operation and that open operation provides the best method for dealing with the tumor and removing it if possible.

Although stereotactic biopsy has been advocated by some as an initial procedure, it is generally not suitable for most pineal region tumors for the following reasons:

1. If removal can be accomplished, then it is best done at the primary operation.

2. Bleeding, if it occurs, can be controlled better by open operation.

3. A sufficient specimen can be obtained by open operation, whereas this may not be feasible by stereotactic biopsy. Frozen tissues are studied by both methods, but the larger specimen obtained by open surgery makes the identification easier for the neuropathologist.

4. With modern neurosurgical techniques, open operations are reasonably safe.

5. Surgical debulking, even without complete removal, can haw a beneficial effect on the response to adjuvant therapy.

Because of the relative ease and safety of stereotactic biopsy, it is generally reserved for those patients who present with obvious tumor dissemination at the time of diagnosis or those whose major medical problems contraindicate an open surgical procedure.

With the increasing use of computed tomography (CT) scanning and especially, magnetic resonance imaging (MRI), we are now encountering a substantial group of patients with lesions of the pineal gland that are mostly cystic but contain a small amount of solid tissue. In most cases the aqueduct has not been compromised and the patients are not symptomatic from their lesion. Initially such lesions were considered to be low-grade cystic astrocytomas but, after surgical removal, they were found to be composed of normal astrocytes and normal pineal cells. Histologically these are pineal cysts and are normal anatomical variations of the pineal gland. As our 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.

Mortality has been most frequent among a group of highly cellular and extremely vascular malignant pineal cell tumors. These tumors can sometimes present with an apoplectic spontaneous haemorrhage. During surgery, obtaining haemostasis can be difficult and postoperative haemorrhage often accounts for an unfavourable outcome associated with this group of tumors. The use of stereotactic biopsy has been no less successful in dealing with this problem. There is hope that specific tumor markers may be developed that can identify these tumors non invasively to avoid such complications.

Diagnosis

The standard diagnostic workup includes CT and MRI scans without and with the administration of a contrast agent and measurement of beta human chorionic gonadotropin and alpha fetoprotein in both the serum and the cerebrospinal fluid (CSF). MRI has proven to be the most accurate diagnostic examination and provides information on tumor characteristics and the anatomic relationships of the tumor with its surroundings. Angiography is only performed if the MRI suggests a vascular lesion such as a vein of Galen aneurysm or arteriovenous malformation. However, despite this broad diagnostic armamentarium, the exact histologic nature of the tumor cannot be determined reliably with surgery.

Certain tumors can be suspected from the appearance of the scans, particularly teratomas that contain multiple germ layers. The radiographic workup does provide relevant information about the following:

1. Size of the tumor, especially its lateral and superior extent.

2. Vascularity of the lesion and the nature of its contents (whether homogenous or heterogeneous).

3. Irregularities of margination and the probability of invasion.

4. Most importantly, the anatomic relationships of the tumor and the surrounding structures. These include tumor involvement of the third ventricle and its position within the third ventricle, extension of the tumor into or above the corpus callosum, superior-lateral extension of the tumor into the region of the ventricular trigone, involvement or compression of the quadrigeminal region and aqueduct by the tumor relationship of the tumor to the anterior cerebellar vermis, and location of the deep venous system.

Anatomy

The vast majority of tumors arise in the region of, and are attached to, the undersurface of the velum interpositum, which includes the choroid plexus, deep venous system, and choroidal arteries. If the tumor invades these important midline structures, the attachment may be minimal or extensive. 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 an anastomosis to the pericallosal arteries and quadrigeminal arteries.

Some tumors extend to the foramen of Monro, but most are centered at the pineal gland, extending anteriorly 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 and this can be recognized through the MRI. Mostly, however, the vein of Galen, internal cerebral veins, basal veins of Rosenthal 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. Most tumors are not highly vascular, with the exception of malignant pineocytomas, hemangioblastomas and hemangiopericytoma. The most important aspects of the anatomy, which can be gleaned by radiologic 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 that may be encountered during surgery .

Hydrocephalus

Most patients present with hydrocephalus. It is generally preferable to place a ventriculoperitoneal shunt 3 to 7 days prior to the definitive tumor surgery to allow the ventricles sufficient time to gradually decompress. Although ventriculoperitoneal shunting carries the risk of peritoneal seeding in the presence of malignant pineal tumors, this occurs only rarely. On occasions where 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. This ventricular drain can be removed or converted to a permanent shunt on postoperative day 2 or 3, depending on which circumstances prevail.

Surgery

Operative Considerations

Common approaches to the pineal region include infratentorial supracerebellar, occipital transtentorial and transcallosal inter­hemispheric approaches. The best approach to use depends on the anatomic location or spread of the tumor, along with a degree of familiarity and confidence that the surgeon has with a given approach.

The infratentorial supracerebellar approach is most commonly used for several reasons:

1. The approach is to the center of the tumor, which begins at the midline and grows eccentrically.

2. The approach is ventral to the velum interpositum and the deep venous system. to which the tumor is often adherent. This minimizes the risk of damage to the vascular drainage of this critical region.

3. The exposure in the sitting position is comparable to that of other routes.

4. No normal tissue is violated on route to the tumor.

5. If the tumor is not removed completely, a shunt catheter can be placed from the third ventricle, over the cerebellum, to the cisterna magna as a modification of Torkildsen's procedure. If the incisura is not blocked by tumor, this may be sufficient to control hydrocephalus.

Either the transcallosal interhemispheric or occipital transtentorial approach is used under the following circumstances:

1. Tumors that extend superiorly, involving or destroying the posterior aspect of the corpus callosum and deflecting the deep venous system in a dorsolateral direction.

2. Tumors that extend laterally to the region of the trigone.

3. In rare cases where the tumor displaces the deep venous system in a ventral direction (often seen with meningiomas).

Under these circumstances the transcallosal interhemispheric approach can provide extensive exposure, although the subtentorial portion of the tumor on the contralateral side of the approach is not easily visualized. This approach requires retraction of the parietal lobe and the disruption of bridging veins between the parietal lobe and the sagittal sinus, creating the potential for venous infarction and retraction injury. Additionally, the veins of the deep venous system usually overlie the tumor, forcing the surgeon to work around them to avoid injury. Like the transcallosal approach, the occipital transtentorial approach has the disadvantage of encountering the deep venous system overlying the tumor, but usually there are no draining veins to the SSS. Once the tentorium is divided, however, this approach permits a wide view of the pineal region with particularly good visualization of the quadrigeminal plate. A major drawback is the high frequency of visual field deficits associated with this approach.

Various positions have been described for these approaches. The sitting-slouched position is used most often for the infratentorial supracerebellar and occipital transtentorial approaches. This position enables gravity to work in the surgeon's favour by helping tumor dissection from the roof of the third ventricle and minimizing blood pooling in the operative field. It does carry the risk of venous air embolism, and of ventricular and cortical collapse with the subsequent collection of blood or air in the subdural space. However, with proper precautions these complications are infrequent. The occipital transtentorial approach often utilizes the three-fourths prone-lateral decubitus position, which, although avoiding many of the complications of the sitting position, does not allow gravity to work in the surgeon's favuor. The Concorde position was developed to combine aspects of both the prone and semi-sitting positions but still has the disadvantage of blood pooling in the operative field.

Infratentorial Supracerebellar Approach

The infratentorial supracerebellar approach is a modification of the technique proposed by Krause, the approach being made through the posterior fossa over the cerebellum. The position of the patient is critical to the smooth performance of this operation. The patient is placed in a sitting-slouched position with the head flexed and held forward by a pin-vise type of head holder so that the body conforms to a C-configuration. The aim is to position the patient's tentorium as close to the horizontal as possible.

Because of the depth of the exposure and the need for magnification and proper illumination, the operative microscope is essential to this operation. The angled eyepieces are reversed and a 275-mm objective is the most utilitarian. To avoid fatigue. arm­rests are needed for the surgeon, who is seated during the operation.

A midline incision is used and a craniotomy is performed, leaving the foramen magnum intact but extending at least to the upper edge of the transverse sinuses and torcular to allow slight upward retraction upon the midline of the tentorium. If a craniotomy is to be performed, the sinuses must first be exposed before the bone over them is traversed with the craniotome.

The cerebellum must be completely relaxed, without any dural tension. This can be accomplished by mannitol administration, shunt insertion or ventricular drainage. The dura is opened in a three-flap fashion and the upper flaps are reflected upward. The central flap is the most critical to maximizing exposure. This allows visualization of the upper surface of the entire cerebellar hemispheres and vermis. The bridging veins across the upper surface of the cerebellum are cauterized and divided to relax the cerebellum. We have not encountered oedema or permanent cerebellar damage from interrupting these numerous bridging veins. Once the veins are divided. the cerebellum drops down because of gravitational forces. After protecting the superior surface of the cerebellum with cottonoid, one self-retaining retractor is placed over the vermis, pulling it posteriorly and inferiorly. The operating microscope is brought in at this point and is initially angled upward. An irrigating system using an 18-gauge spinal needle on the retractor arm is directed to the pineal region and connected to a syringe containing irrigating solution.

With the operative microscope in place, the rostral portion of the vermis is visualized. The arachnoid of the quadrigeminal cistern is often thickened in the presence of tumor and must be opened widely. while damage to the precentral cerebellar vein is avoided. This vein is usually in the midline but can be rostral, caudal or displaced to one side. It is easily identified as the thickened arachnoid is opened. The arachnoid is opened close to the cerebellar edge: this opening is then extended laterally and the free edge of the tentorial incisura is pursued. This exposes small arteries of the choroidal group supplying the posterior surface of the tumor. Laterally, the large veins of Rosenthal are also exposed.

At this point the microscope trajectory is modified horizontally or angled slightly downward to avoid opening the vein of Galen. Cauterizing and dividing the precentral cerebellar vein will expose the large posterior surface of the tumor. With further opening of the arachnoid and cauterization of the choroidal arteries to the tumor, the exposure becomes quite generous. The retractor is moved forward to retract the anterior vermis downward and posteriorly. If the tumor is large, the quadrigeminal plate may be obscured. The tumour's vascularity and degree of encapsulation should be noted and a biopsy taken for frozen-tissue analysis. If the tumor is cystic, its contents may be aspirated with a spinal needle to further decompress the area. If a further superior view is required, a retractor may be placed under the tentorium to elevate it slightly using a self-retaining system.

For tumor removal, we use a group of instruments that have been modified to be longer than normal. These include cautery forceps, dissectors, suction tips. the long-curved tip of the ultrasonic aspirator, tumor forceps and transsphenoidal instruments. Depending on the composition of the tumor, it may be decompressed internally with tumor forceps, suction and cautery, or the ultrasonic aspirator. With gradual decompression of an encapsulated tumor, the margins may be folded into the decompressed area, The superior borders are often adherent, sometimes invading the velum interpositum. These connections must be cauterized and divided without injuring the deep venous system. Inferiorly, the quadrigeminal plate tends to remain obscure and is difficult to expose or dissect from the tumor. Gravity is now working against the surgeon at this point and the tumor must be lifted with either suction or tumor forceps to develop this plane if feasible. With further tumor removal, the interior of the dilated third ventricle is exposed. The tumor may be attached to the wall of the third ventricle. specifically the medial nuclei of the thalamus and the pulvinar. Occasionally there is dense attachment to the quadrigeminal plate. In benign and encapsulated tumors, attachment is rarely a problem and a complete resection is usually possible. At the completion of tumor resection, haemostasis is secured with cautery and various haemostatic agents.

The dura is closed in as water-tight fashion as possible to avoid extradural CSF accumulation and pseudo meningocele formation. The muscles and fascia are closed in appropriate layers. The patient is extubated and sent to the intensive care unit in a semi-sitting position.

Transcallosal Interhemispheric Approach

When a supratentorial approach is desirable, the patient is operated on in the sitting-slouched position with an approach from the non-dominant posterior parietal region. A parietal craniotomy is performed, extending across the midline. The dura is opened in a U-shaped fashion and flapped toward the superior sagittal sinus. The hemisphere is separated from the sagittal sinus and the falx. The trajectory is toward the apex of the tentorium and the posterior portion of the corpus callosum. With large tumors, the corpus callosum is generally thin and is resected over an area of about 2 cm from its posterior aspect. This allows visualization of the dorsal surface of the tumor. If the tumor extends into the posterior fossa, the tentorium is incised from the leading edge posteriorly to the limit of the tumor. On occasions when it is desirable to reach the side opposite to the exposure. a suture may be placed in the tentorium adjacent to the straight sinus to rotate the straight sinus and tentorium until the opposite portion is visualized. With large tumors, the deep venous system is generally displaced laterally to the region of the trigone. Some authors, sometimes divide one of the internal cerebral veins. At its best this exposure provides for a comprehensive view of the entire roof of the third ventricle, laterally to both trigones and down the posterior fossa in the region of the anterior medullary vellum.

Occipital Transtentorial Approach

The occipital transtentorial approach as advocated by Clark and others involves an occipital craniotomy and sectioning of the tentorium. It is usually performed in the lateral or three-fourths prone position with the operative approach on the dependent side so that the occipital lobe falls away from the falx. Occasionally one or two bridging veins between the occipital lobe and the superior sagittal sinus must be divided, which can sometimes lead to visual problems. Optimal exposure is gained by sectioning the tentorium adjacent to the straight sinus. This approach brings the surgeon under the splenium of the corpus callosum. It does have the disadvantage that the surgeon must work around the deep venous system, but it provides excellent exposure of the quadrigeminal region. The high incidence of hemianopsia from retraction of the occipital lobe and the eccentric exposure of the bulk of the tumor, limit its usefulness. The principles of the tumor removal are the same as with the supracerebellar infratentorial approach. The tumor is debulked internally and the capsule is then dissected away from the surrounding structures.

Complications of Surgery

Serious complications of pineal tumor surgery, regardless of the route used, are related to the nature of the tumor and its potential for intra- or postoperative hemorrhage. Haemorrhage has played a major role in most of the surgery-related deaths and can occur with a delay of up to several postoperative days. This phenomenon is most prevalent with pineal cell tumors (pineoblastoma and pineocytoma), which tend to be soft and highly vascular. Haemostasis is difficult both at operation and in the postoperative period. Haemorrhage can occur prior to surgery as a so-called "pineal apoplexy" or can be associated with stereotactic biopsy.

Complications of the sitting position, particularly with the posterior fossa approach, include venous air embolism, hypotension and cortical collapse when hydrocephalus of significant degree is relieved by tumor removal. The incidence of cortical collapse can be reduced by preoperative shunting to allow the ventricular system a chance to accommodate over several days before the major operation. This phenomenon can occur in varying degrees and, although striking on the postoperative CT scan, gradually improves without major neurologic complications for the patient. Subdural shunting is rarely required to relieve chronic hygromas resulting from this complication.

There are unusual and unexpected complications related to the cervical spinal cord and indirectly to the flexed position of the head in the sitting position,especially ifthe patient has local problem in the neck, which could lead postoperatively to a permanent quadriplegia. Another complication could be in an individual with an arteriovenous malformation of the pineal gland which could cause quadriparesis, presumably due to spinal cord stretching from the intraoperative posture.

The complications of the interhemispheric approach are related to retraction of the parietal lobe, with transient sensory or stereognostic deficits on the opposite side. These have not been serious or permanent. Unlike the occipital transtentorial approach, the interhemispheric approach has not been associated with visual field defects.

Regardless of the operative approach used, various pupillary abnormalities, difficulty focusing or accommodating, internuclear ocular palsies and limitation of upward gaze can be expected when the tumor is dissected from the quadrigeminal region. These deficits improve gradually but may last for many months or up to a year before normal function returns. Manipulation of the brain adjacent to the third ventricle can lead to impaired consciousness. The fourth cranial nerve is generally caudal to the tumor and is rarely identified. Of all the cranial nerves in the region, however, it is the closest and injury may result in a specific extraocular palsy. Ataxia has been minimal and usually transient. The incidence and severity of deficits is increased with prior radiation therapy, the presence of symptoms preoperatively, and a high degree of malignant and invasive tumor characteristics.

Shunt malfunction can occur in up to 20 percent of patients following surgery. To minimize this problem, with the infratentorial approach a catheter can be left from the opening in the third ventricle over the cerebellum to the cisterna magna to provide additional CSF diversion.

Postoperative Management

All patients with malignant pineal cell tumors, germ cell tumors and ependymomas should have postoperative staging to look for spinal metastasis. Spinal MRI with contrast is the procedure of choice. We also perform CSF cytology but have not found this to be particularly helpful for guiding management decisions.

All patients with malignant pineal region tumors should receive 4000 cGy to the whole brain with an additional 1500 cGy to the pineal region. The only exceptions to this include the occasional pineal cell tumor or ependymoma with a histologically benign appearance that has been completely excised. In these cases a decision may be made for close follow-up with serial MRI scans while withholding radiation therapy unless the tumor recurs. We do not routinely give spinal radiation unless there is radiographic evidence of tumor seeding.

Chemotherapy is reserved for those patients with nongerminomatous malignant germ cell tumors. In these patients, it is advisable to give chemotherapy first, before radiation therapy. Although some studies have suggested that chemotherapy may be useful for pineal cell tumors and as an adjunct in the treatment of germinomas to reduce the amount of radiation necessary, these results are still preliminary.

Because some tumors may be of a mixed cell type, such as benign teratoma with a small inclusion of germ cell malignancy, detailed and comprehensive evaluation of the specimen is necessary to determine the appropriate mode of therapy. A report of one patient who had a removal of what was considered to be a germinoma. After receiving radiation to the entire neuroaxis, he then returned with massive seeding and recurrence of what was now an embryonal cell carcinoma. The radiation had eliminated the germinoma while a small nidus of embryonal carcinoma (tumor more appropriately treated with chemotherapy) was permitted to run rampant.

Results

An excellent surgical outcome occurs in more than 90 percent of the time. Operative mortality around 4 percent, which in nearly all instances is related to complications of postoperative haemorrhage. Morbidity, mostly involving extraocular dysfunction is minor and usually temporary. Permanent major morbidity occurs in 3 percent of patients. Not surprisingly, risk factors for increased operative morbidity and mortality included malignant tumors, prior radiation therapy and the presence of significant preoperative neurological impairment.

The most common tumors are astrocytomas and germinomas, each representing about 16 percent of all pineal tumors. One-third of all tumors are benign and have been nearly always completely resectable and curable with surgery alone. Among all tumors, benign and malignant, a gross total resection is possible 45 percent of the time. A histologic diagnosis can be made in all patients.

Surgery for all pineal region tumors with removal of benign encapsulated tumors and debulking of malignant tumors is recommended. Large specimens are necessary for accurate histologic typing. Advances in surgical management have led to improved surgical outcome. Additional therapy is based on operative findings, including histologic diagnosis as well as tumor staging for metastatic disease.