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Accuracy of frameless and frame-based image-guided stereotactic brain biopsy in the diagnosis of glioma: comparison of biopsy and open resection specimen
From Neurological Research, 6/1/05 by Woodworth, Graeme

Objectives: Tissue heterogeneity and rapid tumor progression may decrease the accuracy and prognostic value of stereotactic brain biopsy in the diagnosis of gliomas. Correct tumor grading is therefore dependent on the accuracy of biopsy needle placement. There has been a dramatic increase in the utilization of frameless image-guided stereotactic brain biopsy; however, its accuracy in the diagnosis of glioma remains unstudied.

Methods: The diagnoses of 21 astrocytic brain tumors were derived using image-guided stereotactic biopsy (12 frame-based, nine frameless) and followed by open resection of the lesion 7.5 (0.5-4) months later. The histologic diagnoses yielded by the biopsy were compared with subsequent histologic diagnosis from open tumor resection.

Results: Histology of 21 stereotactic biopsies accurately represented the greater lesion at open resection a median of 45 days later in 16 (76%) cases and correctly guided therapy in 19 (91%) cases. Biopsy accuracy of frameless versus frame-based stereotaxis was similar (89 versus 66%, p=0.21). In three (14%) cases, biopsy specimens were adequate to diagnose glioma; however, histology was insufficient for definitive tumor grading. Anaplastic oligodendroglioma (ODG) was under-graded as low-grade ODC in one (5%) case. Biopsy of new onset glioblastoma multiforme (GBM) yielded necrosis/gliosis and was termed non-diagnostic in one patient. Tumors >50 cm^sup 3^ were 8-fold less likely to accurately represent the grade of the entire lesion at resection compared with lesions

Discussion: Both frameless and frame-based MRI-guided stereotactic brain biopsy are safe and accurately represent the larger glioma mass sufficiently to guide subsequent therapy. Large tumor volume had a higher incidence of non-concordance. Increasing the number of specimens taken through the long dimension of large tumors may improve diagnostic accuracy. [Neurol Res 2005; 27: 358-362]

Keywords: Biopsy; craniotomy; glioma grade; pathology; stereotactic


Stereotactic biopsy techniques have been widely utilized for the diagnosis of intra-cranial glioma for many decades1"5. Recently, there has been a dramatic increase in the utilization of frameless image-guided Stereotactic brain biopsy. Current thinking assumes accurate diagnosis of gliomas with both frameless and frame-based Stereotactic biopsy6-8. These techniques provide only a small sample of tissue from a predetermined target point in a radiologically defined lesion. The high tissue heterogeneity and rapid tumor grade progression associated with gliomas may decrease the accuracy and prognostic value of sterotactic biopsy diagnosis.

Previous studies assessing the diagnostic accuracy of frame-based image-guided Stereotactic biopsy mostly compare the immediate frozen section diagnosis with the permanent sections of the biopsy9"12. Other groups have compared the pathologic accuracy of frame-based stereotactic brain biopsy with the tissue diagnosis following open craniotomy in a variety of tumor types7. Authors have generally lumped all mass lesions together and have only looked at small numbers of gliomas7. Two studies have compared frame-based stereotactic brain biopsy specimen to subsequent resection specimen solely in the evaluation of gliomas13'14. However, these studies either compared biopsy and resection specimens from differing institutions, surgeons, and pathologists13 or allowed a mean duration of 6 months between biopsy and open resection specimen14. Furthermore, the accuracy of frameless image-guided techniques in the diagnosis of glioma has not been studied.

We evaluated whether the pathological diagnoses obtained by frameless or frame-based image-guided stereotactic brain biopsy were accurately representative of the greater lesion at the time of open resection in a surgeon- and pathologist-controlled study.


All patients that had undergone image-guided stereotactic brain biopsy followed by open craniotomy for glioma at the Johns Hopkins Hospital between 1995 and 2003 were identified. Patients prior to 2000 underwent frame-based image-guided stereotactic brain biopsy. Following the adaptation of frameless stereotaxis in 2000 at the Johns Hopkins Hospital, all patients in this study underwent frameless image-guided stereotactic biopsy. All biopsy and resection specimens were performed by two surgeons (A.O. and J.W.) and evaluated by a single neuropathologist. Patient demographics, operative variables, clinical outcomes, pathological diagnosis yielded by stereotactic biopsy and open resection, and radiological characteristics of the tumor were retrospectively obtained in all cases. Histological diagnosis of the biopsy and subsequent open resection specimens were compared in patients undergoing the frameless versus frame-based techniques. The association between all recorded variables and the accuracy of biopsy diagnosis was assessed by logistic regression analysis.

Frameless image-guided stereotactic biopsy

In all cases a 1.5 Tesla MRI scanner (GE Medical Systems, Milwaukee, Wl, USA) was used to acquire the preoperative images. Imaging studies were performed the day of or day before surgery. Twelve fiducial markers were appropriately positioned on the surface of the patient's head to enable operating room registration between the equipment and the patient. General anesthesia was induced and the head fixed in a three-point Mayfield clamp secured to the table, lntraoperative image guidance was achieved using a wandbased navigation system (Stealth Station, Medtronic, Broomfield, CO, USA). The guidance tube for the wand and biopsy needle allowed for targeting of the lesion in a 3-D orientation according to the straight trajectory, which was planned with the navigation system's software by defining an entry and target point. The system calculated the positioning accuracy giving a root mean square error and used a matching algorithm to successfully register with the fiducial markers. With the registration process completed and its accuracy confirmed, the biopsy device (SNN-Olivier FreeGuide, Philips Medical Systems, The Netherlands) was then attached to the Mayfield clamp. Areas corresponding to contrast enhancement on MRI were targeted for biopsy in both superficial and deep portions of the lesion. The target was selected and the distance to the site was measured and marked on the Nashold biopsy needle (Radionics, Z Medical, Inc., Baltimore, MD, USA). A 0.5 cm linear incision was made at the defined stereotactic site. A battery-operated drill was used to induce a 3/16 inch opening into the skull and the dura opened with a sharp needle. The biopsy needle was then passed down to the area of the lesion at the previously determined distance. Approximately 8 mm long and 1 mm thick tissue specimens were obtained and sent to pathology for frozen sectioning. If the pathology reading was non-diagnostic, further samples were taken from an additional enhancing region of the lesion.

Frame-based image-guided stereotactic biopsy

The Lesell stereotactic frame (Leksell Stereotactic System®, Elekta Instruments, Atlanta, GA, USA) was used for stereotactic biopsy in all cases. Contrasted T1 MRI images or contrasted CT images were utilized for identification of three biopsy targets and to establish stereotactic coordinates. Areas corresponding to an area of contrast enhancement were targeted for biopsy. All patients received local anesthetic with minimal sedation at the time of surgery. An ~0.5 cm linear incision was made at the defined stereotactic site. A battery-operated drill was used to induce a 3/16 inch opening into the skull. Tissue specimens of 8 mm long and 1 mm thick were obtained with a Nashold biopsy needle. If the tumor was not evident or only radiation injury was evident on frozen section, additional biopsy specimens were obtained.


Patient population

Twenty-one patients underwent the image-guided stereotactic biopsy followed by open resection for glioma between 1995 and 2003. Twelve (57%) underwent frame-based stereotactic biopsy while nine (43%) underwent frameless stereotactic biopsy. The mean age of all patients was 40±14 years, 12 (57%) were male, 11 (52%) presented with recurrent versus new brain tumor, and seven (33%) had received prior external beam radiation therapy. The median (IQR, interquartile range) tumor volume was 40 (16-80) cm^sup 3^. Twenty (95%) were enhancing lesions and 18 (86%) were heterogeneous lesions on MRI. Tumor location was parietal in seven (33%) patients, frontal in six (29%), temporal in four (19%), thalamic in three (14%), and basal ganglia in one (5%) patient. The median (IQR) duration between stereotactic biopsy and open resection was 1.5 (0.5-4) months. Patients receiving frameless versus frame-based stereotactic biopsy had smaller median tumor size and more frequently had thalamic tumors (Table 1). There were no other baseline differences between treatment groups.

Comparison of biopsy and resection specimen

Stereotactic biopsy histology accurately represented the greater lesion at open resection a median of 45 days later in 16 (76%) cases (Table 2). The biopsy specimen alone would have correctly guided therapy in 19 (91%) cases. In three (14%) cases, the biopsy specimens were adequate to diagnose glioma; however, histology was insufficient for definitive tumor grading. Anaplastic oligodendroglioma (ODG) was under-graded as low-grade ODG in one (5%) case. In another case, the biopsy yielded gliosis/necrosis and was determined non-diagnostic in the evaluation of a new brain mass. Upon the conversion to craniotomy, open resection yielded glioblastoma multiforme. Transient arm or hand paresis was noted in three (14%) cases. No permanent morbidity or mortality occurred after biopsy. Asymptomatic biopsy site hemorrhage was noted in two (10%) cases.

Predictors of diagnostic accuracy

Concordance between stereotactic biopsy and open resection diagnosis was similar in frameless (89%) versus frame-based (66%) stereotaxis, p=0.21. An increasing tumor volume (cm^sup 3^) was associated with inaccurate glioma grading (OR, 1.01; 95% Cl, 1.0-1.02, p=0.05). Tumors >50 cm^sup 3^ were 8-fold less likely to accurately represent the entire lesion at resection (OR, 8.8; 95% Cl, 0.9-100, p=0.05). Of nine tumors biopsied >50 cm^sup 3^, four (44%) were not concordant with open resection. Of 12 tumors biopsied


This is the first study to demonstrate that frameless image-guided stereotactic brain biopsy accuracy is equivalent to the frame-based technique for the diagnosis of glioma. This is also the first surgeon- and pathologist-controlled study to evaluate whether a diagnosis obtained by image-guided stereotactic brain biopsy accurately represents the entire glioma when obtained acutely after biopsy in all cases.

The accuracy of the frameless technique was equivalent to the frame-based technique, agreeing with subsequent open resection in 76% of cases, leading to appropriate treatment in all but two cases (91%). In three cases, the lack of necrosis in the presence of highgrade histology on biopsy precluded the definitive differentiation of GBM from anaplastic astrocytoma. In these cases, a non-specific diagnosis of recurrent astrocytoma was given, and a treatment course appropriate for both grades III and IV glioma was suggested. In one case, frameless biopsy remained non-diagnostic despite retrieval of multiple specimens from a new brain lesion. It is plausible that the repetitive retrieval of necrosis and gliosis from this GBM may have resulted from a frame-shift error in stereotaxis, placing the needle in the necrotic center. In these cases, it is appropriate to redo stereotaxis imaging and biopsy at a later date or convert to an open biopsy. The later was performed in this case.

In our series, under-grading high-grade astrocytic tumors at biopsy may have been a result of operative protocols based on the heterogenous radiological appearances of a high-grade astrocytoma. In these cases, stereotactic biopsy of suspected intra-cranial neoplasms was targeted away from hypointense areas of necrotic tissue, biasing the histopathoiogical diagnosis to under-grade grade IV astrocytomas as grade III. Hence, previous authors have suggested that grade III astrocytoma on biopsy should be classified as a GBM13 . If evidence of necrosis was not considered mandatory to diagnose GBM on biopsy specimen in this study, all three anaplastic astrocytomas classified as "recurrent glioma" would have been erroneously diagnosed as GBM. Therefore, it may be appropriate to diagnose these lesions as malignant glioma and refrain from differentiating AA from GBM in this setting.

These results suggest that the diagnosis obtained on stereotactic biopsy is sufficient to predetermine the need for adjuvant therapy at subsequent resection (brachytherapy, gliadel) preventing reliance on frozen section to guide intra-operative decisions on the placement of adjuvant treatments.

An increasing volumetric tumor size correlated with the decreasing concordance between biopsy and resection specimen. In fact, over one-third of gliomas >50 cm^sup 3^ yielded biopsy specimens insufficient for accurate grading. While it is unclear why large gliomas may present a challenge for specific tumor grading with stereotactic biopsy, increasing central necrosis and higher tissue heterogeneity seen in more aggressive and larger gliomas may underlie this phenomenon. Gliomas, characterized by their highest tissue grade, are often simultaneously comprised of necrosis, low-grade glioma, and high-grade glioma. Larger lesions may present a wider geometrical variation in tissue types as an obstacle to small biopsy samples. Increasing the number and varying the location of biopsy specimens may improve biopsy accuracy in this setting.

Few studies have assessed the accuracy of stereotactic brain biopsy based on the tissue diagnosis from subsequent open craniotomy7'13'14. Chandrasoma et al7. reported that frame-based CT-guided stereotactic biopsy resulted in a 92% agreement between biopsy and open resection in 12 non-astrocytic cases, but only a 61% agreement in 13 astrocytic neoplasms. As in our series, under-grading of glioma and misdifferentiation of radiation-associated necrosis from glioma was responsible for the majority of biopsy and resection specimen nonconcordance. Jackson ef al, reported a much larger series of 82 gliomas evaluated by frame-based stereotactic biopsy followed by open resection13. This series demonstrated only 51% biopsy agreement with subsequent resection specimen, which lead to altered clinical management in 33% of cases, suggesting that gliomas present a unique challenge to the accuracy of stereotactic biopsy. It is unclear if this large discrepancy resulted, in part, from differing pathologists' interpretations and varying surgeons' biopsy yield within that study. McGirt ef al, reported 79% concordance between biopsy and open resection specimens. That study found undergrading was the greatest shortcoming of the frame-based technique for glioma diagnosis, and suggested that MRIguided biopsy may yield a more accurate diagnosis (80%) than that previously demonstrated by CT-guided stereotactic biopsy (51 and 61 %)7'13'14. The 76% accuracy observed in our series is similar to the previously reported range of 51-79%7'13'14 and supports the utility of imageguided stereotactic biopsy in the diagnosis of glioma.


Frameless image-guided stereotactic brain biopsy specimens were representative of the larger tumor at the time of biopsy with sufficient accuracy to guide subsequent therapy, suggesting that frameless stereotactic techniques are as accurate as frame-based techniques in the diagnosis of glioma. Increased volumetric tumor size was a prognostic indicator of biopsy sampling error. Multiple biopsies through the long dimension of tumors may improve diagnostic accuracy for larger tumors. Frameless image-guided stereotactic biopsy is a valuable tool in grading intra-cranial gliomas. This may become increasingly important as therapies targeting antigen expression are utilized, allowing appropriate selection of adjuvant therapy based on stereotactic biopsy, and predetermined administration at time of subsequent resection.


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12 Greene GM, Hitchon PW, Schelper RL, et al. Diagnostic yield in CT-guided Stereotactic biopsy of gliomas. J Neurosurg 1989; 71: 494-497

13 Jackson RJ, Fuller GN, Abi-Said D, et al. Limitations os Stereotactic biopsy in the initial management of gliomas. Neuro-Oncology 2001; 3: 193-200

14 McGirt MJ, Villavicencio AT, Bulsara KR, ef al. MRI-guided Stereotactic biopsy in the diagnosis of glioma: Comparison of biopsy and surgical resection specimen. Surg Neurol 2003; 59: 277-282

15 Chandrasoma P, Apuzzo M. Astrocytic neoplasms. In: Chandrasoma PT, Apuzzo, ML, eds. Stereotactic Brain Biopsy. New York, Igaku-Shoin, 1989: pp. 89-109

Graeme Woodworth, Matthew J. McGirt, Amer Samdani, Ira Garonzik, Alessandro Olivi and Jon D. Weingart

Departments of Neurosurgery and Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA

Correspondence and reprint requests to: Matthew J. McGirt, MD, Department of Neurosurgery, 600 North Wolfe Street, Meyer 8-161, Baltimore, MD 21287, USA. [] Accepted for publication October 2004.

Copyright Maney Publishing Jun 2005
Provided by ProQuest Information and Learning Company. All rights Reserved

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