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Neurosurgery:
doi: 10.1227/NEU.0b013e31828bf445
Review: Editor's Choice

Diagnostic Value and Safety of Stereotactic Biopsy for Brainstem Tumors: A Systematic Review and Meta-analysis of 1480 Cases

Kickingereder, Philipp MD*; Willeit, Peter MD‡,§; Simon, Thorsten MD; Ruge, Maximilian I. MD*

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Editor's Choice
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Author Information

*Department of Stereotactic and Functional Neurosurgery, University Hospital of Cologne, Cologne, Germany;

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom;

§Department of Neurology, Medical University Innsbruck, Innsbruck, Austria; and

Department of Pediatric Hematology and Oncology, University Hospital of Cologne, Cologne, Germany

Correspondence: Maximilian I. Ruge, MD, Department of Stereotactic and Functional Neurosurgery, University Hospital of Cologne, Kerpener Straße 62, 50937 Cologne, Germany. E-mail: maximilian.ruge@uk-koeln.de

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.neurosurgery-online.com).

Received September 16, 2012

Accepted January 29, 2013

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Abstract

BACKGROUND: The feasibility and safety of stereotactic biopsy for brainstem tumors (BSTs) are controversial. Although magnetic resonance imaging (MRI) has been reported as the preferred diagnostic tool, histopathological analysis is frequently necessary to establish a definitive diagnosis. Recent advances in molecular characterization of brainstem gliomas—accounting for the majority of BSTs—have revealed several potential targets for molecular-based therapies. Hence, a molecular stereotactic biopsy that combines histopathological diagnosis with molecular-genetic analysis will become increasingly important for patients with BSTs.

OBJECTIVE: We conducted a systemic review and meta-analysis to determine the risks and benefits of stereotactic biopsy for BSTs.

METHODS: A systematic search in PubMed, Embase, and the Web of Science yielded 3766 potentially eligible abstracts. Meta-analysis was conducted on 38 studies describing 1480 biopsy procedures for BSTs. Primary outcome measures were diagnostic success and procedure-related complications. Data were analyzed according to standard meta-analytic techniques.

RESULTS: The weighted average proportions across the analyzed studies were: 96.2% (95% confidence interval [CI]: 94.5%-97.6%) for diagnostic success, 7.8% (95% CI: 5.6%-10.2%) for overall morbidity, 1.7% (95% CI: 0.9%-2.7%) for permanent morbidity, and 0.9% (95% CI: 0.5%-1.4%) for mortality. Meta-regression revealed a significant correlation between diagnostic success rates and the number of biopsy procedures performed annually in each center (P = .011). Other factors did not affect the outcome measures.

CONCLUSION: Stereotactic biopsy of BSTs is safe. It allows exact histopathological diagnosis as a prerequisite for adequate treatment and opens new perspectives for the molecular characterization of these tumors as a crucial first step toward more individualized treatment concepts.

ABBREVIATIONS: BST, brainstem tumor

CI, confidence interval

D-BSG, diffuse brainstem glioma

HGG, high-grade glioma

LGG, low-grade gliomas

TC, transcerebellar

TF, transfrontal

The management of patients with brainstem tumors (BSTs), which account for just 1.6% of central nervous system tumors, is complex and controversial.1 Lesions in this localization may represent various histopathological entities of heterogeneous clinical, biological, and radiological character2-5 that require potentially different treatment regiments, ranging from observation to maximum application of oncological therapies resulting in cure or dismal survival. Consequently, recommendations for diagnostic workup of lesions in this highly eloquent and vulnerable area of the brain are similar in variety and include imaging (magnetic resonance [MR]- or nuclear medicine-based) as a noninvasive strategy and/or surgically obtaining tissue for histological workup as an invasive strategy.

Although magnetic resonance imaging (MRI) is essential for diagnosing BSTs, several studies showed disconcordance between MRI-based and histopathological diagnosis in a considerable number of patients. Schumacher et al6 reported a high sensitivity of 94%, but a low specificity of 43% for MRI in distinguishing tumor from nontumorous disease in a pediatric population. Rachinger et al3 revealed that 30% of adult patients with BSTs received a different biopsy-proven histopathological diagnosis compared with the initial radiological assessment. In their study, the sensitivity and specificity of MRI for diagnosing low- and high-grade gliomas (LGG and HGG) was as low as 63% and 47% for the LGG subgroup and 58% and 62% for the HGG subgroup, respectively. Based on the results of these3,6 and other7-11 studies, tissue confirmation may be frequently necessary for reliably diagnosing—and ultimately, adequately treating—patients with BSTs. In addition, several potential targets revealed recently by molecular characterization of brainstem gliomas are opening the door to potential molecular-based therapies.12-15 This will mean that molecular stereotactic biopsy combining histopathological diagnosis with molecular-genetic analysis16 will become an increasingly important step for providing more individualized treatment for patients with BSTs.

Nevertheless, treatment decisions in most studies are only based on imaging, because many groups consider stereotactic biopsy of BSTs too dangerous, referring to studies reporting transient or permanent morbidity rates of up to 28% or 9%,17,18 and mortality rates of up to 4%.19 However, other studies have demonstrated that stereotactic biopsy can be associated with a substantially lower risk and high diagnostic yields.3,18,20,21 The aim of the present meta-analysis was to precisely determine the risks and benefits of stereotactic biopsy for BSTs to overcome some of the prejudices against this procedure.

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PATIENTS AND METHODS

Search Strategy and Study Identification

The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines22; no protocol for this meta-analysis has been published or registered. Appropriate studies were identified by searching the electronic databases PubMed, Embase, and Web of Science. Search terms included: biopsy or biopsies in combination with brainstem or brain stem or pons or pontine or mesencephalon or midbrain or medulla oblongata or posterior fossa or infratentorial. Searches were limited to human studies published in English from 1980 to 2012. Reference lists from publications retrieved were also examined to identify additional studies. The websites of the American Association of Neurological Surgeons (1997-2010), the Congress of Neurological Surgeons (1997-2012), the American Society of Clinical Oncology (meeting abstracts: 2004-2012; educational books: 2002-2012), and the German Medical Science (2003-2012) were also searched for relevant (meeting) abstracts that fit our inclusion criteria.

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Selection Criteria

Selection of abstracts for full review was conducted by 2 independent investigators (P.K. and M.I.R) based on predefined inclusion and exclusion criteria. Studies were eligible if they reported original data on stereotactic biopsy of BSTs (defined as tumors located in the midbrain, pons or medulla oblongata) including details on procedure-related complications (morbidity, mortality) and diagnostic success rates. Studies were excluded if they: (a) presented a reanalysis of subpopulations already included in other studies; (b) reported on biopsy procedures unrestricted to a certain location, not separately addressing the outcome for the brainstem subpopulation; (c) reported a patient population of less than 10 patients; and (d) were commentaries, technical notes, or review articles summarizing the results of previous series. Furthermore, (e) we excluded those series reporting on nonstereotactic (open) biopsies, because this approach has generally been replaced by stereotactically guided biopsies for diagnosing BSTs.17,21,23-27 Each person reviewed the abstracts independently and generated a list of studies to retrieve for full-text review. Lists were then compared and discrepancies resolved by consensus.

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Data Extraction

A data extraction sheet was prospectively designed to extract all the necessary information. Extraction of data was independently performed by 2 authors (P.K. and M.I.R.). Data were subsequently verified between the 2 authors, and discrepancies were settled through consensus discussion. The following details were extracted: treatment institution, year of publication, duration of study, study design (prospective, retrospective), number of patients, sex, age (mean or median age of the study population), age group (children ≤18 years of age, adults), tumor location, imaging modality used for treatment planning, and the applied biopsy trajectory (transfrontal [TF], transcerebellar [TC]). Furthermore, diagnostic success rates (number of patients with a valid histopathological diagnosis), detailed histopathological results, as well as procedure-related (overall and permanent) morbidity and mortality rates were extracted.

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Statistical Analysis

Study-specific proportions of outcome measures (diagnostic success, overall morbidity, permanent morbidity, and mortality) were transformed by using the Freeman-Tukey variant of the arcsine square28 to attain the symmetry of confidence intervals necessary for statistical combination. Transformed proportions were then combined by using random-effects meta-analyses (parallel analyses were based on fixed-effect models). Consistency of findings across studies was assessed by the I² statistic; values of 25%, 50%, and 75% represent mild, moderate, and severe inconsistency.29 Heterogeneity was assessed with meta-regression by comparing results from studies grouped according to study-level characteristics. Evidence of publication bias was assessed with funnel plots. Sensitivity analysis was conducted by repeatedly calculating the effect size with 1 study omitted per iteration. All analyses were performed with Stata release 12.1 (Stata Corp, College Station, Texas). Statistical tests were 2-sided and used a significance level of P < .05.

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RESULTS

Search Results

The search strategy retrieved 3766 publications (Figure 1). After screening titles and abstracts, 3697 articles did not meet criteria for inclusion in the meta-analysis. Full text was retrieved for 69 studies. Upon reviewing these studies, 35 were eliminated for not meeting inclusion criteria for the meta-analysis. Four additional studies were identified through a hand search of meeting abstracts in the online repository of the American Association of Neurological Surgeons, Congress of Neurological Surgeons, American Society of Clinical Oncology, and German Medical Science. Consequently, 38 studies were included in the meta-analysis.3,6,18-20,23,24,30-60

Figure 1
Figure 1
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Study Population

The key characteristics of the patients and studies analyzed are listed in Table 1. The studies comprised a sample of 1480 patients.3,6,18-20,23,24,30-60 The cohorts varied between 10 and 200 patients, with a median of 39 patients per study. Annually, a median of 4.8 patients received stereotactic biopsy for BSTs in the individual institutions (range, 1.6-11.1 patients per year). Biopsied lesions were primarily located within the pons (49%), midbrain (21%), and medulla oblongata (4%). Affection of more than 1 brainstem area was reported for 22% of patients. Planning of the biopsy trajectory was primarily based on computed tomography (CT) or multimodal imaging guidance, and was a TF approach in the majority of cases (64%).

Table 1
Table 1
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Meta-analysis

The weighted proportions for diagnostic success and procedure-related complications (overall and permanent morbidity, mortality) across the studies are shown in Figure 2. In detail, the weighted average proportion calculated by random-effects modeling was 96.2% (95% confidence interval [CI]: 94.5%-97.6%) for diagnostic success, 7.8% (95% CI: 5.6%-10.2%) for overall morbidity, 1.7% (95% CI: 0.9%-2.7%) for permanent morbidity, and 0.9% (95% CI: 0.5%-1.4%) for mortality. Pooling proportions using fixed-effect models yielded similar results: 97.0% (95% CI: 96.1%-97.8%) for diagnostic success, 6.9% (95% CI: 5.7%-8.2%) for overall morbidity, 1.4% (95% CI: 0.9%-2.1%) for permanent morbidity, and 0.9% (95% CI: 0.5%-1.4%) for mortality. In detail, 5 individual studies reported mortality for 1 patient each.18,19,36,47,61 Cause of death was available for 4/5 patients and included aggravation of peritumoral edema (2 cases: 1 pediatric and 1 adult patient), intraparenchymal hemorrhage (1 case: age not stated), and respiratory distress (1 case: adult patient; no evidence of hemorrhage).

Figure 2
Figure 2
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Sensitivity analysis for random-effects models that calculated pooled proportions upon exclusion of single studies in turn showed similar results, indicating that overall estimates were not driven by the findings of single studies (See Figure, Supplemental Digital Content 1, http://links.lww.com/NEU/A521 [“Leave-one-out” sensitivity analyses of outcome measures (diagnostic success, mortality, overall and permanent morbidity) assessed in the present meta-analysis]). Between-study heterogeneity was absent for mortality (I² = 0.0%, 95% CI: 0.0%-37.0%), mild for permanent morbidity (I2 = 37.5%, 95% CI: 5.8%-58.5%), and moderate for diagnostic success (I² = 53.7%, 95% CI: 32.8%-68.1%) and overall morbidity (I2 = 57.0%, 95% CI: 37.9%-70.2%). Funnel plots of study-specific proportions were approximately symmetrical and most data points were within the funnel area, indicating low evidence for presence of publication bias (See Figure, Supplemental Digital Content 2, http://links.lww.com/NEU/A522 [Funnel plot of outcome measures assessed in the present meta-analysis]).

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Subgroup Analyses

Meta-regression revealed a significant correlation between diagnostic success rates and the number of biopsy procedures annually performed in each center (Figure 3). However, overall or permanent morbidity or mortality rates were not significantly affected by this parameter.

Figure 3
Figure 3
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Other factors, including study design (prospective vs retrospective), biopsy trajectory (TF vs TC), imaging modality used for biopsy planning, tumor location, sex, age group (studies reporting on children vs those reporting on adults), or the mean patient age in the individual studies had no significant influence on the assessed outcome measures.

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Pathological Results

A detailed list of the pathological entities diagnosed throughout the studies included in the present meta-analysis is shown in Table 2. In brief, histopathological evaluation revealed brain tumors in 88.23% of brainstem lesions. Glial neoplasms were found in 76.23% of biopsy samples, metastases in 3.97%, lymphomas in 2.58%, primitive neuroectodermal tumors in 1.84%, and ependymomas in 1.25%. Nonneoplastic lesions—most commonly originating from infectious diseases—accounted for 8.61% of biopsy samples. Stereotactic biopsy was nondiagnostic in the remaining 3.16% of patients.

Table 2
Table 2
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DISCUSSION

Quantifying risks and benefits of certain neurosurgical procedures is often difficult, because available data in the literature are usually level III evidence and frequently derive from limited patient series. Thus, designing a rigorous meta-analysis assessing the risks (morbidity, mortality) and benefits (diagnostic success) associated, in this case, with stereotactic biopsy of BSTs, as well as displaying the variety of histopathological findings, provides important data for neurologists, neuro-oncologists, neuroradiologists, and neurosurgeons communicating with patients and their families about this procedure and its outcome.

So far, the diagnostic management of patients with lesions in the brainstem has remained controversial.3,8,30,43,62-64 Therefore, the following issues had to be addressed: (1) to what extent is MRI as a noninvasive diagnostic tool valid enough for diagnosing BSTs, and (2) can potentially different treatment options or observation be based just on imaging, or (3) should histology be obtained, requiring an invasive approach, which harbors a certain risk for procedure-related complications?

Gliomas are the predominant pathology within the brainstem, accounting for 76.23% of all biopsy samples (Table 2). However, a variety of differential diagnoses such as infectious, autoimmune, vascular, metabolic, and other tumoral entities65 must to be ruled out, because these would require completely different treatment strategies. Although MRI is widely accepted as a well-established diagnostic tool for BSTs,5,66,67 the diagnostic concordance of MR-based imaging with histology obtained by stereotactic biopsy for BSTs varies extensively, ranging from 42% to 100% (Table 3).

Table 3
Table 3
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One major reason to vote against stereotactic biopsy for brainstem lesions is the perceived high-risk profile, which has indeed been reported in small and outdated series.17,19,24-26 With the present meta-analysis on 1480 patients, we are now able to demonstrate that stereotactic biopsy of BSTs yields a high rate of diagnostic success (96.2%) and is associated with a low rate of procedure-related complications (overall morbidity, 7.8%; permanent morbidity, 1.7%; mortality, 0.9%). Overall morbidity and mortality rates for stereotactic brain biopsy in general are reported as approximately 4.9% and 0.7% (mean value from published series with at least 100 patients),68 which are similar to our meta-analyses for BSTs specifically. Moreover, a recent comparison of stereotactic brain biopsies in eloquent and noneloquent regions showed no significant difference with regard to procedural complications and diagnostic yield.69 In general, with careful planning, stereotactic biopsy of BSTs can be considered as equally safe and accurate, in comparison with biopsy procedures outside the brainstem.

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Biopsy Procedures in Pediatric BSTs: Summary of Evidence

BSTs frequently occur in children, accounting for 10.7% of all pediatric brain tumors.1 Diffuse brainstem gliomas (D-BSGs), defined as poorly demarcated and nonenhancing lesions on MRI, are the predominant pathology, accounting for 58% to 75% of all BSTs, and carry a uniformly poor prognosis (median survival less than 1 year).67,70 So far, for these patients, the general consensus is to avoid a biopsy if the MRI characteristics are typical of a D-BSG, because MRI is considered sufficiently reliable in these cases.67 Furthermore, because there is no correlation between survival and histopathological grade of D-BSGs,6,64,71 stereotactic biopsy might not alter the treatment, nor affect the outcome.30,70 So far, the only indication for histopathological confirmation in a child with a diffuse nonenhancing mass in the brainstem would be an atypical clinical or radiological appearance, or when mandated by a study protocol.20,70 A recent survey among pediatric neurosurgeons, however, showed considerable interobserver discordance in interpreting a typical MRI image of D-BSGs and found agreement in only 43.8% of cases.72 Therefore, some authors recommend performing stereotactic biopsy procedures to a greater extent.63,73 In addition, recent advances in molecular characterization of D-BSGs revealed several potential targets (especially receptor tyrosine kinases, eg, PDGFR-alpha, MET, and IGF1R, which are frequently upregulated in D-BSGs12-14) for molecular-based therapies. In this context, biopsy-driven clinical trials will become increasingly important for (pediatric) patients with D-BSGs.15,62,74-76

Other diseases may also cause symptomatic brainstem lesions in children: focal low-grade brainstem gliomas, atypical neurocytoma, primitive neuroectodermal tumors, atypical teratoid/rhabdoid tumors, tuberculomas, toxoplasmosis, encephalitis, pyogenic abscesses, and demyelination.20,21,51,52,61,77 For these cases, obtaining histopathological proof seems necessary because of the wide variety of differential diagnoses, making stereotactic biopsy obligatory for any focal and/or enhancing mass in the brainstem.11,20,27,64

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Biopsy Procedures in Adult BSTs: Summary of Evidence

In adults, BSTs are much less frequent than in childhood, accounting for only 1.5% to 2.6% of all intracranial tumors.1,78 Similar to the pediatric population, diffuse brainstem gliomas are the predominant pathology.65 Although MRI reveals patterns similar to those observed in pediatric D-BSGs, they carry a far better prognosis, with median survival rates of 6.3 to 7.3 years.78,79 Furthermore, histological tumor grade significantly correlates with the outcome of adult patients with brainstem gliomas,64,79,80 unlike the pediatric population.6,64,71 Therefore, an accurate diagnosis obtained through stereotactic biopsy is essentially important, because the diagnostic value of MRI is insufficient in determining the histological grade. Rachinger et al3 reported that a correct identification of LGG and HGG in adults with BSTs could be achieved in only 35% and 27% of cases. Reithmeier et al7 presented similar results: in their study, among 55 adult patients with BSTs, the sensitivity for diagnosing LGG and HGG based on MRI was as low as 41% and 21%. In addition, the variety of differential diagnoses is much more diverse than in children5 and includes neoplastic (eg, metastasis, lymphoma, germinoma, acoustic neuroma), infectious (eg, tuberculomas, toxoplasmosis, pyogenic abscesses), vascular (eg, hematomas, vasculitis, arteriovenous malformations, hypertensive encephalopathy, infarctions), or other diseases (eg, neuro-Behcet, sarcoidosis, progressive multifocal leukoencephalopathy, or demyelinating diseases).65 However, the diagnostic value of MRI is considered insufficient for reliably diagnosing BSTs in adults. Rachinger et al3 reported that neuroradiological assessment differed from histopathological diagnosis in 30% of cases with suspected brainstem gliomas. Thus, treatment decisions that are solely based on radiological findings may have fatal consequences (eg, unnecessary radiation and/or chemotherapy for benign lesions that were mistakenly interpreted as gliomas on radiological assessment).3,11 The authors concluded that tissue diagnosis is mandatory for adequate treatment decisions and should be regarded as standard in adult patients with BSTs.3,7,64

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Technical Considerations

Several techniques for performing a stereotactic biopsy of the brainstem have been described, most importantly the TF approach, which is usually applied for lesions located in the midbrain or upper pons, and the TC approach, which is preferred for lesions in the lower pons or medulla oblongata.81,82 Although the TF approach is longer, it allows sampling of tumors located in all segments of the brainstem. The entry site must be chosen carefully to avoid injury of ventricles, vascular structures, and the tentorium. The TC approach is shorter and passes less eloquent structures on its trajectory. A recent study by Dellaretti et al18 found no significant correlation between the preferred surgical approach and diagnostic success rates, or procedure-related complications. This is in line with the results from our meta-analyses revealing that the biopsy trajectory had no impact on outcome measures (diagnostic success, morbidity, or mortality). Thus, both approaches can be considered safe trajectories with comparable diagnosis success rates.

Of note is that the reported diagnostic yield of 96.2% may be limited by the fact that the majority of studies in our meta-analysis relied only on cross-sectional imaging (ie, CT and/or MRI) for defining the margins of the lesion and the biopsy trajectory. This approach, however, has been shown to be associated with undergrading of BSTs.8,52 Especially gliomas, accounting for the majority of BSTs, are notorious for their heterogeneity, and a small biopsy sample may represent a benign focus in a largely malignant tumor.83,84 Incorporating metabolic imaging such as positron emission tomography (PET) has been shown to increase the diagnostic reliability of stereotactic biopsy for BSTs,8,52 because this method allows the inclusion of hypermetabolic areas (“hot spots”) in the biopsy trajectory; such areas reliably correspond to malignant components of these heterogeneous tumors.85-87 As a future direction, multimodal planning including CT, MRI, and PET may be essential for defining representative biopsy trajectories to increase the diagnostic reliability of biopsy procedures for BSTs. However, the exact value and indications of including metabolic imaging data for defining representative biopsy trajectories in patients with BSTs remains to be determined in future studies.

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Strengths and Limitations of the Present Study

Our systematic review summarizes and synthesizes study level data from diverse sources representing more than 30 years of experience reported in the world literature related to the feasibility, safety, and diagnostic accuracy of stereotactic biopsy for patients with BSTs. However, some limitations of the present study deserve to be mentioned: the majority of studies in our meta-analysis were performed retrospectively and, hence, may be subject to biases related to data collection or participant selection. Moreover, incomplete and/or inconsistent recording of data in the individual studies limits the value of the performed meta-regression analysis. As a consequence, we were not able to reliably determine the influence of the applied imaging modality (eg, presumed superiority of MRI over CT-based planning) and the tumor location (eg, presumed higher procedural risk for lesions located in the medulla oblongata in comparison with the midbrain) on the assessed outcome measures. Despite these limitations, this meta-analysis provides important data for the neuro-oncological community and will also stimulate further research into the optimal use as well as the limitations of this procedure in clinical practice.

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CONCLUSION

Histopathological confirmation of suspected BSTs from MRI should be obtained in the following cases: (a) pediatric patients with any focal and/or enhancing mass in the brainstem to exclude benign/nontumoral disorders; (b) pediatric patients with a diffuse nonenhancing mass in the brainstem meeting most criteria for D-BSGs, but with atypical clinical or radiological presentation; and (c) pediatric patients with a diffuse nonenhancing mass in the brainstem as part of a clinical trial when mandated by the study protocol to enhance molecular-driven investigations that may have a major impact on future treatment of D-BSGs. In contrast to the pediatric population, (d) adult patients with suspected BSTs should undergo histopathological confirmation in each case, because the number of potential differential diagnoses is much more diverse than in childhood. Based on the results of this meta-analysis, stereotactic biopsy can be considered as an important, accurate, and safe diagnostic tool, even for tumors in highly eloquent brain such as the brainstem, when performed by experienced neurosurgeons. It allows the combination of traditional histopathological diagnosis with state-of-the-art molecular genetic analysis, enabling detailed characterization of these tumors, as a crucial first step toward more individualized treatment concepts.

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Disclosure

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

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55. Samadani U, Stein S, Moonis G, Sonnad SS, Bonura P, Judy KD. Stereotactic biopsy of brain stem masses: Decision analysis and literature review. Surg Neurol. 2006;66(5):484–491.

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59. Woodworth GF, McGirt MJ, Coon A, Huang J, Garonzik I, Olivi A. Stereotactic biopsy of the Brainstem: Neurological Sequelae, technical, and diagnostic Considerations. Paper Presented at: American Association of Neurologic Surgeons. [Abstract archive]. Presented at the 73rd Annual Meeting of the AANS; 2005; New Orleans, Louisiana.

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COMMENT

The management of brainstem mass lesions remains controversial, particularly when the lesion cannot be removed and is infiltrating in nature, while the benefits of stereotactic procedures are still debatable.1

The use of stereotactic biopsy in the diagnosis of brainstem tumors has become less popular; this is particularly true following the publication of the studies by Epstein2 and Epstein and McCleary.3 The authors published 2 articles in consecutive years condemning the biopsy of these tumors. In 1985, Epstein2 stated that a small biopsy specimen does not appear to provide useful information. Epstein and McCleary3 followed this a year later with the comment that no consistent useful information could be obtained from biopsy samples.

Additionally, some authors have reported that in patients with brainstem tumors not amenable to surgery, diagnosis should be based only on MRI findings, except in cases of atypical lesions, because such lesions are associated with a diagnosis of tumors that are different from diffuse gliomas. However, the literature does not clearly report which MRI findings define an atypical lesion.4

Over the past few years, some centers have shown renewed interest in stereotactic biopsy of brainstem lesions. Certain studies have produced interesting results; however, these studies only report individual center experience.5-7

The present study demonstrated that biopsy sampling is a safe procedure and can provide useful information regarding patient treatment.

Safe because a precise histological diagnosis was established in 95.88% of cases, and the cumulative overall and permanent morbidity rates related to stereotactic biopsy were 8.12% and 1.92%, respectively, whereas the (cumulative) procedure-related mortality was 0.35%;

Useful because a diagnosis of glioma was determined in 77.07% patients and in the remaining cases, histological diagnosis verified a wide variety of comorbidities, including metastasis, lymphoma, inflammatory disease, and others. Thus, in relation to the therapeutic consequences of radiotherapy and radiochemotherapy, patients with pathologies different from diffuse glioma probably gained some benefit from the biopsy procedure, particularly patients with no histological evidence of tumor, in which treatment based on radiological diagnosis could have had severe consequences.8

In the past few decades there have been numerous advances in neuro-oncology. Consequently, it is highly probable that conventional fractionated radiotherapy will not remain the only efficient treatment in diffuse brainstem glioma over the next few decades. Indeed, stereotactic radiotherapy and new chemotherapies, gene or immunotherapies, alone or in combination, will succeed in improving the outcome of these patients.9 These therapies will inevitably require tissue sampling for diagnostic confirmation and tumor grading, for molecular marker studies, or for immunological purposes, before the adoption of the target therapies.10

Marcos Dellaretti

Júlio Leonardo Barbosa Pereira

Belo Horizonte, Brazil

1. Dellaretti M, Touzet G, Reyns N, et al.. Correlation between magnetic resonance imaging findings and histological diagnosis of intrinsic brainstem lesions in adults. Neuro Oncol. 2012;14(3):381–385. View Full Text | PubMed | CrossRef Cited Here... |

2. Epstein F: A staging system for brain stem gliomas. Cancer. 1985;56(7 suppl):1804–1806. Cited Here...

3. Epstein F, McCleary EL: Intrinsic brain-stem tumors of childhood: surgical indications. J Neurosurg. 1986;64(1):11–15. Cited Here...

4. Dellaretti M, Pereira JLB. Editorial: brainstem glioma. Response. J Neurosurg: Pediatrics. 2011;8:537–538. Cited Here...

5. Schumacher M, Schulte-Montig J, Stoeter P, Warmuth-Metz M, Solymosi L. Magnetic resonance imaging compared with biopsy in the diagnosis of brainstem diseases of childhood: a multicenter review. J Neurosurg. 2007;106(2 suppl):111–119. Cited Here...

6. Pincus DW, Richter EO, Yachnis AT, Bennett J, Bhatti MT, Smith A: Brainstem stereotactic biopsy sampling in children. J Neurosurg. 2006;104(2 suppl):108–114. Cited Here...

7. Dellaretti M, Reyns N, Touzet G, et al.. Stereotactic biopsy for brainstem tumors: comparison of transcerebellar with transfrontal approach. Stereotact Funct Neurosurg. 2012;90(2):79–83. PubMed | CrossRef Cited Here... |

8. Rachinger W, Grau SJ, Holtmannspoetter M, Herms J, Tonn JC, Kreth FW. Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared to MRI only. J Neurol Neurosurg Psychiatry. 2009;80(10):1134–1139. View Full Text | PubMed | CrossRef Cited Here... |

9. Selvapandian S, Rajshekhar V, Chandy MJ: Brainstem glioma: comparative study of clinico-radiological presentation, pathology and outcome in children and adults. Acta Neurochir (Wien). 1999;141(7):721–726. Cited Here...

10. Jeuken JW, Van der Maazen RW, Wesseling P. Molecular diagnostics as a tool to personalize treatment in adult glioma patients. Technot Cancer Res Treat. 2006;5(3):215–229. Cited Here...

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CME QUESTIONS

1. What is the mortality rate of stereotactic brainstem biopsy for suspected brainstem malignancy?

a. 1%

b. 3%

c. 5%

d. 7%

e. 9%

2. What is the most common brainstem pathology that requires stereotactic biopsy in the adult population?

a. Infection

b. Inflammatory lesion

c. Metastasis

d. Glioma

3. What is the diagnostic success rate of a stereotactic brainstem biopsy for a suspected tumor?

a. 40-54%

b. 55-69%

c. 70-84%

d. 85-99%

Keywords:

Brainstem tumors; Diagnostic yield; Meta-analysis; Procedural complications; Stereotactic biopsy

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