Pineal region tumors represent 0.4% to 1.0% of intracranial tumors in American literature. Obtaining a tissue diagnosis is the cornerstone of the rational management of pineal lesions. The initial surgical decision involves choosing between a stereotactic biopsy and open microsurgical procedures. Open resection facilitates the maximal removal of tumor volume and has diagnostic accuracy and improved prognosis. Stereotactic biopsy is less invasive and has a lower risk of complications. A review of all major series reporting stereotactic biopsy for pineal region lesions reveals a mean diagnostic yield of 94%, with a morbidity of 1.3% and a mortality of 8.1%.
Pineal region tumors are rare, accounting for 0.4% to 1.0% of intracranial tumors in American and European literature and 4% in Japanese literature. A myriad of tumor subtypes arise in this region, which reflects the heterogeneous nature of the pineal gland. The pineal region lies deep within the cranium, and is closely related to the brainstem and the critical deep venous structures, and the complexities of which have led to a long-standing debate regarding the management of both benign and malignant lesions in this location. Except in rare instances of elevated germ cell markers where histologic confirmation is not necessary, a rational management strategy for pineal region lesions almost always begins by obtaining a tissue diagnosis. A histologic diagnosis can be obtained via direct operative approaches, stereotactic biopsy, and endoscopic transventricular approaches, with the primary objective being establishment of an accurate histologic diagnosis. Given the wide variety of histologic subtypes and mixed tumor pathologies, diagnostic accuracy is essential for making enlightened management decisions. In addition to important prognostic significance, the histologic subtype drives the use of adjuvant therapy, need for metastatic workup, and follow-up decisions. This review focuses specifically on the indications, methodology, accuracy, and safety of stereotactic biopsy for pineal region lesions.
Principles of stereotactic biopsy
Background
Frame-based stereotactic systems translate a point on a 2-dimensional image into a 3-dimensional target. There are many frame-based stereotactic systems, with the Cosman-Roberts-Wells (CRW) (Integra Lifesciences Corp, Plainsboro, NJ, USA) frame among the most popular. The CRW works on an arc radius system, allowing the aiming arc to be moved in 3 spatial places according to the obtained target coordinates. Thus, the focal point of the arc corresponds with the target. Other popular frames include the Leksell (Elekta, Stockholm) and the Brown-Roberts-Wells (BRW).
Patient Selection
Unless CSF or serum markers are positive, thereby confirming a diagnosis of a malignant germ cell tumor, surgical intervention in all patients with pineal region lesions is advocated. The initial surgical decision frequently involves choosing between stereotactic biopsy and open microsurgical procedures. Zealous advocates can be found for either strategy; however, each modality is most effective when used for specific indications rather than applied exclusively for all lesions. Open resection facilitates the maximal removal of tumor volume and provides the benefits of diagnostic accuracy and, in many cases, improved prognosis. Stereotactic biopsy has the advantage of being less invasive, can be performed without the need for general anesthesia, and is associated with an overall lower risk of complications. Stereotactic biopsy is, therefore, favored in patients whose medical comorbidities preclude open surgical resection, patients with multiple lesions, and in the setting of lesions with radiographic evidence of brainstem invasion where open surgery may be of limited value. Further indications include a presentation suggestive of an infectious etiology or of metastatic cancer associated with diffuse systemic disease. Although most pineal region lesions may be safely biopsied, an individual analysis must be made based on the lesion’s location, size, and composition, paying close attention to adjacent neural and vascular structures.
Biopsy Technique
The safety of transit through the brain has been greatly improved by modern imaging and planning software that facilitates the preoperative reconstruction of the stereotactic trajectory. Many variations and nuances exist in the actual performance of stereotactic biopsies of deep-seated lesions at various institutions; however, the basic principles are consistent. As part of their initial evaluation, patients undergo fine-cut contrast-enhanced magnetic resonance imaging (MRI) of the brain. This MRI allows for an in-depth analysis of the lesion in question, and including a fine-cut sequence provides the substrate for accurate image reconstruction during stereotactic planning. On the day of the surgery, a CRW frame is placed (typically with local anesthesia and no sedation) in the preoperative area. After obtaining a fine-cut computed tomography (CT) or MRI scan, patients are transported to the operating room. Alternatively, the frame may be placed with the aid of monitored anesthesia care or under general anesthesia, if necessary, and then transported to radiology for imaging with anesthesia. Patients are then positioned on the operating room table in the supine position with the head neutral, slightly elevated, and fixed to a Mayfield adapter to ensure rigid fixation during the biopsy procedure.
Concurrently, the stereotactic planning is performed on a computer workstation located within the operating room sterile core. The authors’ institution currently uses Brainlab iPlan Stereotaxy (Brainlab, Westchester, IL, USA) for stereotactic planning, but several commercially available platforms are available. First, the CRW frame is localized within the computer system. Then the CT and MRI scans are merged using commercially available software. Although auto-merge features are used, the accuracy of the merge must be confirmed by the surgeon to ensure an accurate and safe plan before proceeding with the target/trajectory selection.
The pineal region is roughly defined as the area of the brain bounded by the splenium of the corpus callosum and the tela choroidea dorsally, the quadrigeminal plate and tectum of the midbrain ventrally, the posterior aspect of the third ventricle rostrally, and the vermis of the cerebellum caudally. Targets are generally selected within regions of avid contrast enhancement, preferably in the center of the lesion to facilitate placement of the midpoint of the window of a Nashold biopsy needle (Integra Lifesciences Corp, Plainsboro, NJ, USA) within the lesion. Various trajectories can be used based on preoperative imaging, which, in the current era, would include a contrast-enhanced MRI study, although the majority of older studies relied on CT imaging. The biopsy trajectory can be orthogonal lateral, oblique anterolateral (anterolateral superior), or posterolateral ( Fig. 1 ). Although no data convincingly demonstrate the superiority of one trajectory over another, a low frontal approach that stays below the internal cerebral veins is ideal and is the most commonly used approach. This trajectory traverses the frontal lobe and internal capsule such that optimal entry points and targets can be chosen to minimize pathways through ependymal surfaces and adjacent vasculature. A posterolateral approach via the parieto-occipital junction can be used, but is probably most appropriate for lesions with significant lateral and superior extension.
After the target and entry points are chosen, a probe’s-eye view is used to ensure that pial, ependymal, and vascular elements are avoided and that the frame is set according to the determined coordinates. In the operating room, all frame settings and measurements must be meticulously checked. The use of a phantom system with the CRW frame is particularly helpful to ensure that all instruments are confirmed with reference to the target point. Once patients are properly sedated, the procedure may proceed. The importance of skillful neuroanesthesia cannot be overstated to allow for a safe biopsy. Local anesthesia with mild sedation is usually sufficient and further minimizes morbidity associated with general anesthesia while allowing for periodic neurologic assessment of patients. Access to the cranium can be obtained via a twist drill or through a more substantial burr hole at the proposed entry site. A small burr hole is favored to allow for direct visualization to avoid possible entry through a sulcus; however, either approach is reasonable. A Nashold side-cutting biopsy needle is used to obtain the specimen. After passing the biopsy needle to the proper depth, a small amount of suction is applied and held for several seconds before the rotation of the inner sleeve to amputate the specimen. The specimen is evacuated using a gentle saline irrigation through the biopsy needle. To begin, 2 samples are routinely retrieved to allow for a smear, frozen, and standard permanent pathologic analysis. It is helpful to pay attention to the directionality of the biopsy window and initially take the 2 specimens from different orientations based on the imaging characteristics. Should bleeding occur, steady irrigation should be performed with cool saline until the bleeding clears. Specimens are picked up immediately by the neuropathologist and reviewed with the operating neurosurgeon. Until a diagnostic result is obtained, the outer sheath of the needle should remain in place to facilitate additional biopsies if necessary.
Frameless Stereotactic Biopsy
Frameless neuronavigation techniques were introduced in the 1990s and have since evolved into a viable method of stereotactic biopsy in select circumstances. The technology has been embraced by many neurosurgeons and is supplanting frame-based techniques in general neurosurgical practice. Briefly, a fine-cut MRI or CT scan is obtained and an intraoperative registration is achieved using either scalp fiducial markers or surface merging. These procedures are often performed under general anesthesia to eliminate any potential patient movement. The patients’ head is fixed in a 3-point Mayfield clamp, and using a proprietary neuronavigation system, patients are registered, and the entry/target points are chosen in the same manner as previously described for frame-based procedures. Frameless neuronavigation technology is rapidly improving and advances, such as preregistered biopsy needles, navigation without rigid fixation, and novel systems with mechanical probe holders to maintain a fixed trajectory, are sure to improve the safety and efficacy of frameless stereotactic biopsies. However, because of the lengthy trajectories required for pineal region biopsies, the margin of error is generally greater for frameless compared with frame-based systems.
There are no studies that specifically examine the frameless stereotactic biopsy for pineal region lesions and, in fact, pineal region lesions are excluded from several series. Overall, the literature comparing frameless to frame-based biopsy would suggest that the safety and efficacy are comparable. Smith and colleagues, however, concluded that although equally efficacious, the frame-based approach required less anesthesia resources, less operating room time, and shorter hospital stays and should be considered the first-line approach for stereotactic brain biopsy. Lunsford and colleagues report on their vast experience performing stereotactic biopsies and reaffirm the safety profile of frame-based biopsies and point out several significant advantages compared with frameless systems, including precise image integration, twist-drill access, preplotting of probe pathways, ability to use intravenous sedation without intubation, and a high degree of precision. They went on to compare their outcomes using frame-based biopsies with published outcomes using frameless approaches and demonstrated a 2.9% and 0.075% morbidity and mortality for frame-based versus 8.6% and 1.5% for frameless systems. Thus, although frameless systems are available and have been gaining increased popularity, frame-based image-guided systems for pineal region biopsies are preferred because of their widespread availability, ease of use, and consistent accuracy.
Special Considerations in Children and Uncooperative Patients
Stereotactic procedures require specific modifications when performed in children. A primary limitation is the inability for most children to cooperate with the procedure. Many children are unable to tolerate application of the head frame. Thus, general anesthesia is typically required for children (and uncooperative or agitated adults) with intubation performed before the application of the CRW frame. The other consideration in children is the size and integrity of the skull. Infants often have incompletely ossified skulls, and dural or cortical penetration is a risk with overzealous pin tightening. Strict age or size cutoffs for use of the CRW system do not exist, but children with a head circumference of 25 cm or greater can be secured with pediatric pins and safely biopsied.
Anesthetic Considerations
A successful pineal stereotactic biopsy depends on cooperation between surgeon, anesthesiologist, and patient. This relationship is facilitated by effective patient preparation regarding expectations and the nature of the procedure. These procedures are ideally performed with monitored anesthesia care using gentle amnestic sedation and generous local anesthesia, thus providing cooperative, comfortable, and safe patients. In the case of children or uncooperative patients, it may be necessary to use general anesthesia. This practice allows the use of muscle paralysis and absolutely still patients, thus, allowing safe passage of the biopsy needle. The use of general anesthesia, however, eliminates assessment of neurologic function and is associated with its own morbidity and mortality unrelated to the procedure. Critical attention to blood pressure management is also crucial to minimize the risks of hemorrhagic complications.
Pathologic Considerations
Compared with open biopsy, image-guided stereotactic biopsy provides the advantage of obtaining tissue from a predetermined target within the lesion. The major disadvantage remains the small size of the biopsy cores, which may result in possible sampling error. This factor is especially true with pineal region lesions, which are often heterogeneous in nature. For instance, different degrees of malignancy may exist within regions of a pineal neoplasm resulting in an inaccurate diagnosis. Proper handling and interpretation of stereotactic biopsy specimens is crucial to deriving meaningful information and, thus, justifying the risks of the procedure.
Biopsy specimens are placed in a petri dish with saline and are picked up immediately by the on-call neuropathologist. The operating surgeon provides critical information concerning the clinical history, imaging characteristics, and consistency of the lesion. These factors must be taken into consideration to properly assess the cytologic features and correctly diagnose the lesion. A smear is often prepared as the initial step in tissue processing. If a diagnosis can be rendered, the remainder of the tissue is fixed for permanent pathology. If the smear is not diagnostic, a frozen section is typically performed. If a diagnosis still cannot be rendered, additional specimens may be requested. The decision to obtain additional specimens must take into account the reliability of the frozen specimen diagnosis, the risk of bleeding, and the likelihood of tumor heterogeneity. A nondiagnostic specimen should prompt a reevaluation of the target and trajectory along with a reverification of the stereotactic coordinates. A firm lesion may be shifted by the end of the needle without actually penetrating the capsule and may require adjustment of the angle of trajectory or an increase in length. In some instances, the firmness of the tumor may not permit a specimen through the simple suction provided with a Nashold-type needle. A decision may be made to use a cup forceps or cutting biopsy needle to obtain the specimen. The surgeon must take into account the significantly increased risk of bleeding inherent in such a decision.
Perioperative Management
Standard neurosurgical care dictates the management of these patients, but a few critical points deserve mention. Within the first 24 hours postoperatively, patients are monitored in the neurologic intensive care unit and employ strict blood pressure control (systolic blood pressure less than 140 mmHg). Perioperative antibiotics are administered, but steroids or antiepileptics are not routinely used unless the clinical scenario dictates. Patients undergo immediate postoperative CT scans without contrast to rule out intracerebral hemorrhage and to establish a baseline should a neurologic deficit manifest itself. Patients are typically discharged in 24 to 48 hours postoperatively.
Literature review
Methods
An inclusive PubMed search performed for English-language articles published from 1990 to February 1, 2011, with the keywords pineal, tumor, region, biopsy, and stereotactic, returned 1001 articles. Of those, 60 articles were relevant to the biopsy of pineal tumors or the pineal region. Only those studies containing greater than 5 pineal region tumors represented in the article or in which pineal region tumors comprised greater than 10% of the patients/tumors in the study were included for analysis. Ultimately, 8 studies were analyzed and relevant data tallied into tabular format ( Table 1 ). Mean percentage is provided when possible.
Related posts:
On the Surgery of the Seat of the Soul: The Pineal Gland and the History of Its Surgical Approaches
Preoperative Evaluation of Pineal Tumors
Surgical Approaches to the Pineal Region
Minimally Invasive Approaches to the Pineal Region
Clinical Outcomes after Treatment of Germ Cell Tumors
Contemporary Management of Pineocytoma
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