NEUROSURGERY

CLINICAL STUDIES

Pineal Region Tumors and the Role of Stereotactic Biopsy: Review of the Mortality, Morbidity, and Diagnostic Rates in 370 Cases

Jean Regis, M.D., Pablo Bouillot, M.D., Françoise Rouby-Volot, M.D., Dominique Figarella-Branger, Ph.D., M.D., Henry Dufour, M.D., Jean C. Peragut, M.D.

Département de Neurochirurgie (JR, PB, HD, JCP), Service d'Information Médicale (FR-V), and Service d'Anatomopathologie (DF-B), A.P.M., Centre Hospitalier Universitaire la Timone, Marseille, France

OBJECTIVE: It is classically considered that the morbidity and mortality rates are greater for stereotactic biopsies of pineal region tumors, compared with tumors in other regions. However, to date, the number of cases studied in the literature has been insufficient to evaluate these parameters and compare them with the morbidity and mortality rates for stereotactic biopsies of tumors located elsewhere.

METHODS: With the aim of evaluating these parameters, we reviewed 370 stereotactic biopsies of pineal region tumors, from 15 French neurosurgical centers. We statistically verified the absence of heterogeneity of the different French centers with regard to diagnostic, mortality, and morbidity rates. In contrast, statistical heterogeneity was clearly seen for the large stereotactic biopsy series (for all tumor locations) in the literature.

RESULTS: The mortality rate was 1.3% (5 patients of 370), and 3 patients suffered severe neurological complications. This study is the first to clearly demonstrate that the mortality, morbidity, and diagnostic rates for stereotactic biopsies are not different in the pineal region.

CONCLUSION: Our conclusion is that stereotactic biopsy must remain a main diagnostic modality for tumors of the pineal region.
(Neurosurgery 39:907­914, 1996)

Key Words: Brain tumors, Pineal region, Stereotactic biopsy, Stereotaxy, Third ventricle

Tumors of the pineal region, because of their close association with critical vascular and brain structures (41), are well known to pose problems for microsurgery. Classically, open surgical resection is associated with a high risk of morbidity and mortality. In the earlier operations, the operative mortality rate after direct surgery was 30 to 70% and the morbidity rate was up to 65% (46). Thus, a conservative approach was advised (irradiation after a drainage procedure, with surgery being reserved for tumors that failed to respond). It was argued that 75% of pineal tumors are malignant, are rarely amenable to surgical excision, and are radiosensitive (1, 36, 48). This management was associated with an overall mortality rate of less than 5% and a 5-year survival rate of 60 to 75% (85% for germinomas) (1, 26, 28, 36, 46). Improvements in microsurgery and anesthesia have greatly reduced mortality and morbidity rates for direct surgery (33, 54, 55, 57). Despite the advances in microsurgical techniques, excision of pineal tumors remains difficult (10).

A wide variety of tumors occur in the pineal region. Of these tumors, 25% may be subjected to primary surgery, being benign, encapsulated, and/or radioresistant. For 75% of these tumors, a conservative approach is theoretically preferable, with these tumors being malignant and/or radiosensitive (1, 36, 48). Distinguishing the histological types of various tumors remains a main goal for the improvement of treatment planning (2, 3, 6, 11, 21, 51). Sometimes several histological components are mixed in the same tumor, requiring a different management strategy and producing considerable difficulty in diagnosis (13).

Stereotactic biopsies in the pineal region have been reported to be dangerous. The rare series in the literature report no deaths and negligible morbidity (14, 37, 43). However, tumors in the pineal region are relatively rare, and these series include a small number of patients. To evaluate the mortality rate, morbidity rate, and diagnostic yield for the largest population of patients possible, we organized a national inquiry in France (49).

PATIENTS AND METHODS

Between 1975 and 1992, 15 French neurosurgical centers involved in stereotaxy (see the list of investigators under Acknowledgments) performed 7885 stereotactic biopsies. Of this total, 370 tumors (4.7%) were of the pineal region. According to Ringertz et al. (52) and Pendl (44), this region was 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. We have chosen this wide definition because of the similarity of problems encountered with all tumors of this region, even though some are not primarily from the pineal body.

This is a retrospective study. A questionnaire was used for the collection of data. Patients presenting with a tumor in the pineal region (as defined above) without strong evidence (cerebrospinal fluid [CSF] cytological, blood and CSF marker, and radiological analyses) for diagnosis were selected for biopsy.

The age range was 2 to 73 years; for 70% of these patients, age ranged from 10 to 73 years. The gender ratio was 3 male:2 female patients.

Of these 15 centers, 8 used mainly or only the Talairach frame, 2 used mainly or only the Leksell frame, 2 used both of these frames, and 3 used another system. Most of these biopsies were performed with "Sedan's needle," only 23% with forceps, and none with Backlund's instrument. For patients from the earlier period, ventriculography was commonly performed, but now this technique is rarely used.

When the trajectory was orthogonal lateral, telemetric angiography was always performed. Stereotactic computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) is currently used. The approach was orthogonal lateral or oblique anterolateral in most cases; it was rarely posterolateral.

We consider the mortality rate to be directly related to the biopsy procedure itself. The morbidity (new deficit or deterioration of a preexisting deficit) was, in our study, separated into severe (coma, akinetic mutism, or other long-term, severe, neurological consequences) and slight (transient neurological deficit, hydrocephalus, Parinaud syndrome, etc.). Patients were examined by the neurosurgeons pre- and postoperatively, with clinical follow-up during the months after the procedure. The diagnostic yield was calculated by dividing the number of biopsy procedures leading to definitive histological diagnosis by the total number of procedures.

The different comparisons between the population distributions were evaluated with the chi2 statistics test. An analysis of variance was used to compare the mean ages for the different histological types.

RESULTS

The chi2 test showed no differences among the various neurosurgical centers of our series in terms of mortality rate, morbidity rate, or diagnosis. This result shows that our series is homogeneous for mortality, morbidity, and diagnostic rates. This allowed us to group these results and analyze them together.

Morbidity and mortality rates

The mortality rate was 1.3% (n = 5). In each of these cases, a postoperative CT scan showed hematoma.

Three patients (0.8%) showed postoperative, long-term, severe, neurological deterioration (long-term coma and akinetic mutism). In 27 patients (7%), a slight transient neurological deficit was noted. Among these 35 complications, a hematoma of the pineal region was found on the CT scan 11 times (of a total of 16 complications exhibiting hemorrhage). Seeding along the biopsy trajectory was noted for only one patient (0.27%). There was no case of infection.

Diagnostic yield and pathological features

The diagnostic yield was 94%. In 19 cases (5%), the biopsy did not lead to a diagnosis (no tissue or no pathological response).

For four patients (1%), the first histological diagnosis seemed to be wrong, as determined after open surgery or after a second histopathological examination. For five patients (1.3%), the results seemed to be incomplete for tumors combining several different histological types, of which only one was identified in the biopsy. In these cases, histological determination was completed after surgical removal proposed in the "first intention" or after partial responses to radiotherapy and/or chemotherapy. It is difficult to assume that in the remaining cases the histological diagnosis based on the biopsy was correct and complete, but the clinical course was consistent with the diagnosis that was assigned. In 346 cases (93.5%) the stereotactic biopsy influenced the treatment strategy, proving definitive for a surgical approach or a nonsurgical one and helping determine the choice of nonsurgical approach. Thirty-eight percent of patients underwent a surgical procedure in line with the biopsy result. The 24 remaining cases include the 5 deaths and 19 failures.

We used the histopathological classification of Russel and Rubinstein (53). The three most common histological types (Table 1) were germinomas (27%), pineocytomas/blastomas (24%), and astrocytomas (26.5%). Distribution by age for each histological type corresponds to classical data (27, 40, 53) and are summarized in Figure 1. The tumors able to secrete common tumor markers (19, 20, 25, 32, 47, 55, 56, 60) constituted only 2.5% of all specimens in this study and 9.2% of the germ cell tumors (placental alkaline phosphatase not available before 1992).

The heterogeneity of the material lead us to evaluate the heterogeneity of our results, to estimate their validity. To evaluate the diagnostic value of age, we separated the histological types classified as highly curable by radiation from the others. The analysis of variance showed a statistical difference (P = 0.0001) in mean age in relation to histological type, with an apparent threshold at 30 years.

TABLE 1. Distribution of Histological Types
Histological Type No. of Tumors
Germinomas 101
Astrocytomas 98
Pineoblastomas 45
Pineocytomas 44
Other tumors of neuroglia (24)
Ependymomas 16
Oligodendrogliomas 6
Ganglioneuromas 2
Pineal cystsa 10
Other germ cell tumors (26)
Teratomas 16
Embryonal cell carcinomas 6
Choriocarcinomas 4
Others (22)
Metastases 10
Meningiomas 10
Lymphomas 2
aDefined as nonneoplastic glial cysts within the pineal gland.


FIGURE 1. Relationship between age and histological type.

Separating patients into two age groups (Group I, <30 yr; Group II, >30 yr), we studied the distribution of radiosensitive (germinomas only or germinomas and pineoblastomas) and nonradiosensitive (P = 0.00001 [10-5] or P = 0.00000001 [10-8] for germinomas only) histological types. Of the patients less than 30 years of age, 51.2% had radiosensitive tumors, whereas 18.8% of the patients over 30 years of age had them. Of the patients with radiosensitive tumors, 84.2% were under 30 years of age. Of the patients with nonradiosensitive tumors, 51.7% were under 30 years of age.

Correlations among mortality rate, morbidity rate, probe trajectory, type of instrument, and pathological features

We tried to correlate morbidity rate, mortality rate, and diagnostic failure with the clinical, histological, and technical parameters. In all five cases of death, the probe trajectory was orthogonal lateral, but statistical analysis did not show a relationship between the choice of trajectory and the risk of morbidity (P = 0.32).

In the five cases of death, a hematoma was discovered in the CT scans. In three of them, the tumor was a pineoblastoma (patients were 55, 61, and 67 yr of age). The instrument used for the biopsy was a Sedan's needle in three cases and a forceps in two cases.

It is noteworthy that most cases of severe complications (without death) occurred with hard tumors. After histological examination, it was found that these hard tumors were teratomas, pineocytomas, and an astrocytoma of the pineal body.

Comparisons of mortality rate, morbidity rate, and diagnostic yield for stereotactic biopsies in the pineal region and in other brain areas

After proving the homogeneity of our material, we compared our results for mortality, morbidity, and diagnostic rates with those previously reported in the larger series of stereotactic biopsies in the literature, without consideration of location (4, 8, 18, 24, 29, 30, 34, 35, 42). These large series were chosen after an exhaustive study of this subject in the literature. We retained the most important series and those that were well described.

The average diagnostic yield was 93.74%, compared with 94% in our series. The average mortality rate was 0.81%, compared with 1.3% in our series. The average severe morbidity rate was 3%, compared with 0.8% in our series.

The use of the cross-tabulation test (chi2) applied to the number of deaths, complications, and diagnoses among these series in the literature showed statistically significant differences. This heterogeneity does not allow a global comparison between our series and the series in the literature. Therefore, we proceeded with pairwise comparisons. We failed to find any statistical differences for mortality rate (P = not significant), morbidity rate (P = not significant), or diagnostic rate (P = not significant).

DISCUSSION

Trial radiotherapy of pineal region tumors leads to the inappropriate irradiation of patients with benign or radioresistant tumors (1, 26, 28, 36, 46), without any benefit and, sometimes, especially in children, with delays in development or other radiation-induced injuries. With 30 to 50% of pineal region tumors being radioresistant, we consider this empirical irradiation unacceptable (20, 57). This point of view could change with the availability of radiosurgery (7, 12, 16) for selected patients (L. Manera, J. Regis, O. Chinot, D. Porcheron, O. Levrier, P. Farnarier, J.C. Peragut, submitted for publication).

Because of improvements in microsurgical techniques, the direct surgical approach can be recommended today. Resection provides accurate histological diagnoses with reduced mortality rates. However, there is still morbidity/mortality and only a small number of tumors can be resected completely. The mortality rate after microsurgical resection of pineal tumors is between 5 and 10% (25, 57). Postoperative complications include new visual defects, epidural fluid collection, infection, and cerebellar ataxia (10, 39, 50, 57).

A gross total resection has been reported in 0 to 69% of the patients (50, 57). The benefits of an incomplete or subtotal resection should be discussed. Some authors think that a subtotal resection promotes adjuvant radio- or chemotherapy, whereas others think that it does not and that open surgery causes CSF and brain seeding of malignant cells (26).

Total resection seems possible with meningiomas, epidermoid tumors, and benign teratomas (10, 50, 55). However, subsequent reports indicated that 60 to 80% of the tumors in this region are radiosensitive (20, 26, 28, 36, 58). In our series the lower number of 51% can be explained by the small number of pediatric cases. With this direct surgical method, some pineal region tumors will be incompletely resected, with a mortality/morbidity risk that is unnecessary because they are radiosensitive; for most of these tumors, additional therapy is required.

Therefore, determination of the accurate histological diagnosis is very important. Despite their improvement, imaging techniques fail to provide this diagnosis (15, 22, 23, 31, 37­39, 59, 61, 62). MRI can yield precise localization. In only a few cases, i.e., mature teratoma (computed tomography and MRI) or meningioma (computed tomography, MRI, and angiography), neuroradiological diagnosis is accurate enough for a therapy decision to be made.

In a previous report (8), we demonstrated with 3052 patients that stereotactic biopsies (for all locations) provide a high level of accuracy (90%), a low mortality rate (0.6%), and a low morbidity rate (3%). In the special case of pineal region tumors, however, this has not been shown conclusively.

Conway (14) and Moser and Backlund (37) reported no deaths and no severe complications. These biopsies were performed on the CT scan area, and those authors reported a high rate of nondiagnostic biopsies. Pecker et al. (43) reported only 1 nondiagnostic biopsy among 25 biopsies of pineal region tumors. More recently, Dempsey et al. (17) reported 15 biopsies in the pineal region, yielding histological diagnoses in all patients, with no related mortality or morbidity.

Eperonnat (21) and Peragut et al. (45) reported three deaths after biopsies of pineal tumors. All of the series in the literature (5, 9, 14, 17, 29, 37, 43) are too small and inappropriate for accurate evaluation of the real diagnostic yield, mortality rate, and morbidity rate. Our series of 370 stereotactic biopsies of the pineal region tumors allowed us to evaluate these rates, to compare the former with the rate for stereotactic biopsies in general, and to consider the use of stereotactic biopsy in the management of pineal region tumors.

However, pineal region tumors are rare, i.e., 3 to 8% of intracranial tumors in children and 0.4 to 1% in adults (36, 53, 54). In our study, 5% of the stereotactic biopsies are in the pineal region, emphasizing the usefulness of this procedure in this region despite its danger. To obtain enough cases, additional series must be added. Thus, the main statistical bias to analyze in this large series was its heterogeneity. These biopsies were performed between 1975 and 1992 in 15 centers. Four centers (Rennes, Marseille, Paris-Saint Anne, and Lille) performed 70% of these biopsies (256 biopsies) and worked for many years with very similar techniques, according to the teaching of J. Talairach. Moreover, we statistically verified the absence of heterogeneity among the different centers for diagnostic, mortality, and morbidity rates. In contrast, statistical heterogeneity is clearly seen among the large series of stereotactic biopsies (all locations) in the literature, mainly for minor complications whose definition is different with different authors. However, these series cover different periods, with major technical differences explaining the heterogeneity of their results. This study is the first to clearly demonstrate that the mortality, morbidity, and diagnostic rates of stereotactic biopsies are not different in the pineal region.

Complication avoidance

Dempsey et al. (17) think that the chosen trajectory is important for complication avoidance and often use low frontal approaches to stay below the internal cerebral veins, but we failed to demonstrate a relationship between complications and trajectory. Most cases of severe complication occurred with hard tumors (pineocytomas, teratomas, and an astrocytoma of the pineal body). In all of these cases, the neurosurgeon encounters a hard tumor that is difficult to penetrate as the instrument pushes it away. Most of the failures were also related to hard tumors. Since this study, the evidence of the histological value and danger of such hardness has led to a change in our procedure. In cases of failure after the first attempt to penetrate the tumor, we stop the procedure and adopt a microsurgical approach for removal and diagnosis. A higher overall risk of morbidity correlating with "hard tumors" cannot be established rigorously in the absence of knowledge of the number of hard tumors in the population that are biopsied without complication. The evidence that 84.2% of the patients with radiosensitive tumors (germinomas and pineoblastomas) were younger than 30 years does not radically change our method of management but emphasizes the role of microsurgery for patients older than 30 years and of radiotherapy for younger patients.

Limits of the study methodology

This is a retrospective study allowing compilation of a huge number of tumors from pineal region biopsies (compared with previous reports), and the main goal is to define the mortality and morbidity rates for this procedure. The questionnaire was centered on this aim and did not allow testing for additional correlation between technical aspects and morbidity rate, mortality rate, and diagnostic yield.

In the early part of the series (1975­1979), we suspect that some tumors could have originated from adjacent regions and not from the pineal body. This would explain the considerable number of astrocytomas in this population. With regard to the mortality and morbidity evaluations of the biopsies from this region, we have considered this acceptable.

The value of 94% for the diagnostic yield is questionable, because the diagnosis was considered accurate when the following criteria were met: 1) histological examination gave a diagnosis, 2) this diagnosis was confirmed in cases in which an open surgical procedure was performed, 3) no discrepancy was observed with blood and CSF markers and CSF cytological findings, and 4) the clinical course was consistent with the diagnosis. One can argue that some heterogeneous tumors can remain among cases meeting these criteria; however, the patients responded positively to nonsurgical management, and we can assume that in all of these cases, the biopsy played its role correctly in the therapeutic decision-making process.

Conclusion

In our large series, stereotactic biopsy for tumors of the pineal region seems to be a safe and effective way to provide a histological diagnosis. The mortality (1.3%) and morbidity (0.8%) rates are not higher and the diagnostic yield (94%) is not lower than in other locations. The risk of seeding is very low. Stereotactic biopsy provides a histological diagnosis and thus allows one to choose between microsurgical and nonmicrosurgical treatment. The stereotactic biopsy of pineal region tumors thereby forestalls the microsurgical treatment of radiosensitive tumors and radiotherapy of radioresistant, (potentially) totally resectable, benign tumors. Other ways of obtaining histological diagnoses, such as CSF cytological or tumor marker analyses, are rarely conclusive in this series but in some cases can avoid the risk of a biopsy. A prospective study would be necessary to evaluate more precisely and rigorously the factors associated with complications and to elaborate on the technical issues for pineal tumors biopsies, which are of great importance. To guide subsequent treatment, we think that histological diagnosis is necessary and that stereotactic biopsy is the safer and more efficient way to obtain this.

ACKNOWLEDGMENTS

We thank M. Choux for advice and the following people for contributions to the investigation: D. Legars, Hôpital Nord (Amiens, France); F. Cohadon, Hôpital Pellegrin Tripode (Bordeaux, France); J. Chazal, Hôpital Fontmaure (Chamaliéres, France); A. Benabid, Centre Hospitalier Universitaire (CHU) des Sablons (Grenoble, France); S. Blond, CHU Lille (Lille, France); J.-J. Moreau, CHU Dupuytren (Limoges, France); P. Farnarier, O. Levrier, E. Eperonnat, D. Gambarelli, N. Graziani, and F. Grisoli, CHU de la Timone (Marseille, France); J.L. Barat, Hôpital St. Julien (Nancy, France); Y. Lajat and D. Menegalli Boggelli, Hôpital Laennec (Nantes, France); B. Devaux, Hôpital St. Anne (Paris, France); F. Hor, Val de Grace (Paris, France); J.-P. Nguyen, Hôpital Henri Mondor (Paris, France); D. Scarabin, CHU de PontChaillou (Rennes, France); J. Brunon and M.-J. Motuo Fotso, Hôpital Bellevue (St. Etienne, France); and J. Sabatier, CHU de Purpan (Toulouse, France).

Received, February 21, 1996.
Accepted, June 12, 1996.
Reprint requests: Jean Regis, M.D., Service de Neurochirurgie Fonctionnelle et Stéréotaxique, CHU La Timone, 264 rue St. Pierre, 13385 Marseille, CEDEX 05, France.

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COMMENTS

This article by Regis et al. comprises an aggregate 17-year experience of 15 French centers performing stereotactic biopsies of pineal region lesions. This article clearly shows that stereotactic biopsy procedures with pineal region lesions are not only accurate but also safe. The overall mortality rate was 1.3%; the morbidity rate was 7%. These results include procedures performed with several types of stereotactic frames, two types of biopsy instruments, and two surgical approaches. Seeding was noted in only 1 patient of a series of 370 patients. The diagnostic yield was 94%, which is similar to the yield with stereotactic biopsies in other locations.

There are some neurosurgeons who think that stereotactic biopsy has almost no role in the management of pineal region tumors. With little experience and ignorance of the literature, they pronounce stereotactic biopsy in this area too "risky" and preach open procedures, which seem, even in their hands, to have more risk than ever documented in any series of stereotactic biopsies of pineal region lesions.

Some lesions, such as germinomas, are not benefited by resection. Germinomas represent 27% of the patients in the present article. These lesions are better managed with chemotherapy and radiation therapy. These modalities seem just as effective despite the amount of "residual" tumor remaining. I see nothing to be gained from an open procedure in a patient with a germinoma if an accurate histological diagnosis can be established with a carefully performed stereotactic biopsy.

However, in my opinion, an open resection is indicated for most of the other lesions of the pineal area, including pineoblastomas, pineocytomas, teratomas, and pilocytic astrocytomas. Nonetheless, I see little problem in excluding germinomas in young male patients by means of stereotactic biopsy before proceeding with a more ambitious surgical procedure if a histological type other than germinoma is documented.

Contrary to neurosurgical "wisdom," the risk of stereotactic biopsy is small in general and equally small for pineal lesions, as is well documented in this very timely work. The diagnostic yield is high, and the benefit of saving patients with germinomas a more extensive surgical procedure is significant.

Patrick J. Kelly
New York, New York

The authors report a precise statistical analysis to evaluate the validity of stereotactic biopsy for pineal region tumors. I think the data, consisting of a large number of cases cooperatively accumulated from 15 French neurosurgical centers, demonstrate the real features of the mortality, morbidity, and diagnostic rates for stereotactic biopsy of tumors in this region. Although I do not deny the value of stereotactic biopsy, I prefer open direct surgery for pineal region tumors, rather than stereotactic biopsy. The reasons are that techniques for microsurgery have advanced greatly and the safe removal of the tumor can be performed without mortality and hazardous postoperative bleeding. Germ cell tumors often have heterogeneous histological components of mixed tumors, such as germinoma and teratoma. With open surgery, we can remove enough tissue for an accurate diagnosis. Recent magnetic resonance imaging has accurately shown the morphological patterns of the tumors and can predict the histological type far better than in the past decade. For instance, a teratoma can be well differentiated from a germinoma or pineocytoma. Anaplastic astrocytoma or glioblastoma does not extend into the third ventricle but does extend into the parenchymal brain tissue.

I do not hesitate to try radiotherapy without biopsy in some, but not all, cases. We carefully select the cases before such radiotherapy. We never irradiate pineal region tumors in infants before histological verification. We generally administer chemotherapy first for germ cell tumors in infants, after histological verification. We never give trial radiotherapy to tumors suspected to be teratomas or epidermoid cysts. We give trial radiotherapy for pineal region tumors only in cases of suspected germinoma (by magnetic resonance imaging). Local radiosurgery with a gamma knife for those tumors has produced definite and complete responses, without complications. The selection of stereotactic biopsy, open surgery, or radiotherapy at the initial stage of treatment should be decided on a case-by-case basis, with full consideration of meticulous imaging diagnoses, tumor marker examinations, the age and gender of the patients, etc.

Kintomo Takakura
 Tokyo, Japan

Regis et al. accumulated a large series of pineal region stereotactic biopsies from 15 centers (performed between 1975 and 1992). As the friendly debate continues over management strategies for pineal region tumors (empiric radiation therapy, microsurgical resection, stereotactic biopsy, radiosurgery, or chemotherapy), this report is useful and adds more fuel to the fire. Because most neurosurgeons think that knowing what a tumor is helps guide management, the diagnostic steps of imaging plus histological sampling are important for selected patients. If, even with the highest quality magnetic resonance imaging scan, we really do not know what a tumor specifically is (e.g., meningioma versus pineocytoma), how can we properly recommend treatment? For extraaxial tumors with well-defined borders that can be cured with microsurgery, resection is appropriate. For a tumor whose nature is one of intrinsic invasiveness, microsurgery can never provide a total cure, unless some kind of biological therapy is also used. The role of stereotactic biopsy is to help guide this process, and Regis et al. have compiled a large series. Whether the histological diagnosis achieved during their stereotactic surgery appropriately guided management is unknown. Nevertheless, they tell us that the histological diagnosis was confirmed by microsurgery in all cases in which microsurgery was performed, there was no discrepancy between markers and histological type, and the clinical course was consistent in other patients (i.e., no surprises were found).

Traditionally, the pineal region has been considered by many to be a "no man's land" for stereotactic biopsy. As these authors show, this need not be the case. Although the pineal region is surrounded by critical parenchymal structures and by important arteries and veins, safe biopsy trajectories can be tailored for specific patients to avoid complications. The renaissance of cranium-base surgery has seen the identification of numerous "approaches," and the same must be seen for stereotactic procedures. We have advocated a low frontal approach to the pineal region (almost via a midforehead entry point) that provides entry into the lateral ventricle (should cerebrospinal fluid sampling be warranted) and remains inferior to the internal cerebral veins and the roof of the third ventricle. An anterior entry into the tumor is facilitated away from the regional venous anatomy. With this approach, we have not had a hemorrhage. With refinements in the technical aspects of stereotactic biopsy, which have significantly improved safety, the key issue is whether a biopsy should be performed in the first place. Patients with smaller metastatic tumors or meningiomas might undergo radiosurgery as a first approach. Patients with a tumor whose diagnosis is unclear require a tissue diagnosis. The frequency of germinomas and the high success rate of radiation therapy and management for them keeps our interest in stereotactic biopsy high, especially for such patients, for whom microsurgical resection is not usually needed. In a recent article by Kanno (1), the results of microsurgery for 30 pineal region tumors were provided. Only four patients had poor outcomes (three died); however, two of the patients had a germinoma and one an astrocytoma, histological diagnoses that might have been better treated without open resection. In summary, this large series provides safety and efficacy data similar to those for stereotactic biopsy in other brain regions and again indicates the usefulness of stereotactic biopsy in the pineal region.

Douglas Kondziolka
Pittsburgh, Pennsylvania

  1. Kanno T: Surgical pitfalls in pinealoma surgery. Min Inv Neurosurg 38:153­157, 1995.

Because of the wide variety of tumors that occur in the pineal region, obtaining a tissue diagnosis is essential for rational management of therapy and follow-up. Stereotactic biopsy can be a useful method for obtaining tissue in selected cases of pineal region tumors. Regis et al. compiled the results of stereotactic biopsies for pineal region tumors from 15 neurosurgical centers in France and found that mortality and morbidity rates for this procedure are relatively low. The main drawbacks to stereotactic biopsy are diagnostic inaccuracies and impediments to treatment resulting from the residual tumor burden. Without the benefit of long-term follow-up in this series, it is likely that the diagnostic inaccuracy was underestimated beyond the 28 cases in which the diagnosis was unobtainable or was found to be erroneous after craniotomy.

Because of its relative ease and low morbidity rate, we have found stereotactic biopsy for pineal tumors to be useful in patients with multiple lesions, clearly invasive tumors, or medical conditions that contraindicate more extensive procedures. For most patients with pineal tumors, however, we prefer open resection, not only to increase the diagnostic accuracy but also to improve the outcome by reducing the tumor burden before radiation or chemotherapy. Benign pineal tumors and certain pineal tumors that are considered malignant, such as well-differentiated ependymomas and pineocytomas, can often be treated with open resection alone.

Jeffrey N. Bruce
Michael Fetell
Neuro-oncologist
New York, New York

Please submit your thoughts or comments to William Chandler, Internet Moderator at wchndlr@umich.edu.

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