Photodiagnosis and Photodynamic Therapy (2007) 4, 71—75
Photodiagnosis for frameless stereotactic biopsy of brain tumor Fumio Yamaguchi MD, PhD a,∗, Hiroshi Takahashi b, Akira Teramoto a a
Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan b Department of Neurosurgery, Nippon Medical School Musashikosugi Hospital, Kosigi-cho, Nakahara-ku, Kawasaki 211-8533, Japan Available online 3 November 2006 KEYWORDS 5-ALA; Glioma; Malignant lymphoma; Photodynamic diagnosis; Stereotactic biopsy
Summary Stereotactic biopsy is a minimally invasive method of reaching a pathological diagnosis. However, it is not always possible with this method to obtain the tissue samples required for an exact pathological diagnosis. The factors that can make histological diagnoses uncertain are the heterogeneity of tumors and/or brain shifts in the case of small tumors. In this study, we investigated the usefulness of fluorescence in determining the existence of tumor components in obtained tissues. Six patients underwent stereotactic biopsy. 5-Aminolevulinic acid (5-ALA) was administered orally prior to operation. Frameless stereotactic biopsies were performed. The obtained samples were irradiated with 405 nm light and all samples showed red light excitation. Intraoperative rapid pathological diagnosis was made in each case by microscopic examination of frozen section samples. The final pathological diagnoses were of three glioblastomas, one astrocytoma grade 3, and two malignant lymphomas. One case was initially thought to be gliosis on rapid pathological diagnosis, but the final pathological diagnosis reached by examination of a permanent HE stained section was astrocytoma grade 3. Another case, finally diagnosed as malignant lymphoma, was initially diagnosed as infiltration of lymphocytes. The discrepancies between rapid and permanent pathological diagnoses might be caused by the destruction of cells. 5-ALA photodynamic diagnosis is not influenced by the destruction of tissues, simply because it does not depend on the structure of tissues. Stereotactic fluorescence biopsy is very useful in that it enables rapid and exact biopsy and obviates the necessity of waiting for an intraoperative report from a pathologist. © 2006 Elsevier B.V. All rights reserved.
Objective ∗ Corresponding author. Tel.: +81 3 3822 2131; fax: +81 3 5685 0986. E-mail address: [email protected] (F. Yamaguchi).
Frameless biopsy with a neuro-navigator is regularly performed for deep-seated tumors, multiple lesions, and in cases where the removal of a tumor
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2006.09.005
72 would lead to deterioration in the patient’s ADL. In this procedure, rapid pathological diagnosis is essential, and this means that tumor tissues sometimes remain undetected in the obtained specimens [1]. The reason tumor components are occasionally not detected on rapid pathological diagnosis may be the destruction of tissues in the freezing process. Photodynamic diagnosis with 5-aminolevulinic acid (5-ALA) has been widely performed for the last several years in many institutes in Japan and Germany to detect brain tumors like gliomas. The procedure is simple [2—4], and postoperative patient care is easier than that following the use of other photosensitizing agents [5]. We have been using 5-ALA fluorescence diagnosis during stereotactic biopsy procedures in a rapid and effective method we call stereotactic fluorescence biopsy.
Patients and methods Between June 2004 and May 2005, six consecutive patients with brain tumors required biopsies. The final pathological diagnoses for these patients
F. Yamaguchi et al. were four gliomas and two malignant lymphomas. Twenty mg/kg body weight of 5-aminolevulinic acid dissolved in 50 ml of 5% glucose solution was administered orally to each patient 1 h prior to the induction of anesthesia. If the patient was unconscious or unable to swallow, the 5-ALA solution was administered through a gastric tube. Frameless stereotactic biopsies were carried out with a neuro-navigator (Stealth Station® , Medtronic SNT, Louisville, CO, USA). The entry point and target point were planned respectively, and a Hennig Instrument GuideTM (Elekta, Stockholm, Sweden) [6] was used to hold the biopsy needle. The needle’s route was determined to avoid eloquent areas and large arteries and veins. A blue laser system (VLDM1, M&M, Tokyo, Japan), which emits 405 ± 1 nm blue light with a power output of 20—60 mW, was used as the light source for fluorescence diagnosis. The obtained specimens were irradiated with 405 nm blue light and observed for red light excitation. Approval of this procedure was obtained from the ethics committee of Nippon Medical School. Informed consent was obtained from the patients and their families.
Figure 1 (A) Gadolinium-enhanced T1-weighted MR images. Gadolinium-enhanced small masses (white arrows) were found in the left frontal lobe. These images suggest malignant glioma. (B) The target point and the entry point were set to avoid important structures (pyramidal tract, visual pathway, language cortices and vessels). (C) Blue-laser light induced the obtained specimen to emit red light, showing that it contained viable tumor cells.
Photodiagnosis for frameless stereotactic biopsy of brain tumor Table 1
1 2 3 4 5 6
73
Summary of cases undergoing fluorescence biopsy
Patient age
Sex
Preoperative diagnosis
Rapid pathology
Red light emission
Final pathology
58 57 78 68 51 71
F M M F M M
GBM GBM GBM Malignant glioma ML ML
GBM GBM AstroG3 Reactive gliosis Lymphocyte ML
+ + + + + +
GBM GBM AstroG3 AstroG3 ML ML
GBM: glioblastoma multiforme, AstroG3: astrocytoma grade3, ML: malignant lymphoma.
Results Representative case (Case #4) A 68-year-old woman developed systemic tonic convulsions. On admission, she exhibited consciousness disturbance and right hemiparesis (MMT2/5). The lesion on MRI was an irregular enhancing mass with surrounding edema in the left frontal lobe (Fig. 1A). These findings suggested that the tumor was highly invasive and not well demarcated. A primary brain tumor, such as a glioma, was suspected in the differential diagnosis. However, a pathological diagnosis was necessary to plan appropriate treatment. We were concerned that total removal of the tumor would lead to postoperative deterioration of her neurological symptoms, so we decided on a stereotactic biopsy followed by adjuvant therapies. The patient underwent a frameless stereotactic biopsy. The target point chosen was the enhanced lesion, and it was confirmed that there were no eloquent areas along the biopsy needle’s trajectory. The needle was registered as a probe on the neuronavigator, and its insertion was monitored on the navigator’s guidance-view (Fig. 1B). Postoperative CT confirmed that the specimen had come from the planned target (Fig. 2). Red light excitement was observed on irradiation with blue light (405 nm) of the obtained specimen (Fig. 1C). The sample was submitted for rapid pathological diagnosis, which revealed glial cell hyperplasty. However, no neoplasm could be confirmed in the tissue, so the diagnosis was gliosis. The final histopathological diagnosis reached by examination of a permanent HE stained section was astrocytoma grade 3.
Other cases The samples obtained from the other patients all showed red luminescence. Case 5, which rapid diagnosis had indicated was lymphocytic invasion, was found to be a malignant lymphoma postoperatively when a permanent preparation was examined. The
Figure 2 The precise biopsy point was reconfirmed by post-operative CT scan.
permanent diagnoses agreed with the rapid pathological diagnoses in the other cases (Table 1).
Discussion Although stereotactic biopsy is a non-invasive method of arriving at a pathological diagnosis, the diagnosis cannot always be relied on [7]. Diagnostic uncertainty can normally be accounted for by heterogeneity of the neoplasm and/or brain shifts causing displacement of the target. The purpose of this study was to determine whether fluorescence diagnosis is useful in confirming the composition of neoplasms in biopsy samples. For a frame-based biopsy, a frame has to be fixed to the patient’s head before image examination,
74 and this can cause both physical and mental discomfort. The advantage to the patient of a frameless biopsy is, therefore, obvious. Another great advantage of performing a biopsy with a neuro-navigator is the discretion it allows in setting the entry point and target point on a monitor, and the ability to confirm the trajectory through the brain structure. The entry point should be set to avoid any eloquent areas, venous sinuses or large vessels so as not to damage them. The trajectory of the biopsy needle should not pass through the pyramidal tract, association fibers connecting the language cortices, or ventricles. Paying attention to these points minimizes the risk of additional neurological damage and intracerebral hemorrhage. Another advantage of biopsy with a neuro-navigator is that as many target points as necessary can be established. If the targeted tumor is heterogeneous, samples from multiple sites are necessary as a matter of course to reach a correct diagnosis and to understand the tumor’s biological activities. Accuracy is an important consideration in comparing frameless with frame-based biopsies. The mean error of a neuronavigator is 2.75 mm [8], and the Hennig Instrument GuideTM used with a navigator has a mean error of 3.8 mm over a 58 mm route [9], as determined by MRI (Viewing Wand, Elekta Instrument AB, Stockholm, Sweden). In most cases, such errors are insignificant. However, carrying out a precise biopsy from the locus planned preoperatively may be difficult when the lesion is very small, especially if there is a large brain shift. In such cases, fluorescence diagnosis can rapidly determine whether the obtained tissue contains tumor components or not, and another target point can be selected when the specimen shows no red light irradiation. The standard method of preparing a specimen for rapid pathological diagnosis is freezing, as it allows quick preparation of the section sample. The disadvantages are that preparation of thin sections and serial sections is difficult, and that the tissue easily disintegrates [7]. And if there is a breakdown of cells and tissue in the frozen section, it is almost impossible to arrive at a correct diagnosis [10]. Once 5-ALA has entered neoplastic cells, however, the level of protoporphyrin IX (PpIX) in the mitochondria increases, as a result of which red light can be excited by blue light even in disintegrated tissue. Because there is little breakdown of cells and tissue, examination of permanent preparations postoperatively is much more likely to lead to a correct diagnosis than examination of frozen sections. This is a great advantage of fluorescence diagnosis. In fact, rapid pathological diagnosis led to incorrect diagnoses in two of our four cases; correct diagnoses were made only after the tissues in
F. Yamaguchi et al. which red color had been confirmed were submitted as permanent preparations for examination later. The tissues submitted for rapid diagnosis presented red fluorescence, and there seem to be limits to the effectiveness of rapid diagnosis based on frozen sections, even when the tissues are the same as those used for permanent preparations. Negative answers from the pathology department on the existence of tumor components in collected tissue lead to repeated biopsies from multiple sites, which in turn lead to more brain tissue being damaged and extended operation time. Such disadvantages can be overcome by our method: the operation can be terminated once fluorescencepositive tissues are obtained. Stereotactic biopsy is especially recommended in the diagnosis of malignant lymphomas [11], and we believe it should become a standard method. On the other hand, the disadvantage of this fluorescence method is its unavailability for tumors which do not take up 5-ALA or produce protoporphyrin IX, resulting in no fluorescence. Our cases were expected to show fluorescence, because preoperative image analysis strongly suggested the diagnoses eventually reached, and malignant gliomas and malignant lymphomas are known to show strong fluorescence. However, there may be false-negative neoplasms, which do not show fluorescence. Kaneko reported that 25 samples out of 61 malignant glioma samples (41%) did not show fluorescence [2]. Therefore we must be very careful for false-negative cases. In addition, macroscopical fluorescence is not expected in low-grade gliomas or inflamed tissues, so this method will be unsuitable for diagnosing them [2]. Moreover histological diagnosis cannot be made by fluorescence diagnosis. Needless to say, fluorescence diagnosis cannot distinguish between glioblastoma, anaplastic astrocytoma and malignancy lymphoma and histopathological diagnosis gives accurate and exact histological diagnosis. When the fluorescence is weak, confirmation of PpIX fluorescence by spectroscopy is an option; however further analysis is necessary to determine whether tissues with weak fluorescence are actually the tumors we expect. The development of new tissue-labeling substances taken in by the neoplasms of low-grade malignancies can be expected.
Conclusion Stereotactic fluorescence biopsy is a safe and useful method. Fluorescence diagnosis, especially with 5-ALA, is a method with few complications that enables quick and exact biopsies.
Photodiagnosis for frameless stereotactic biopsy of brain tumor
References [1] Hall WA. The safety and efficacy of stereotactic biopsy for intracranial lesions. Cancer 1998;82:1749—55. [2] Kaneko S. Intraoperative photodynamic diagnosis of human glioma using ALA induced protoporphyrin IX. No Shinkei Geka 2001;29:1019—31 (in Japanese). [3] Stummer W, Stocker S, Wagner S, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acidinduced porphyrin fluorescence. Neurosurgery 1998;42: 518—26. [4] Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 2000;93:1003—13. [5] Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 1997;68:31—7. [6] Brommeland T, Hennig R. A new procedure for frameless computer navigated stereotaxy. Acta Neurochir (Wien) 2000;142:443—7.
75
[7] Firlik KS, Martinez AJ, Lunsford LD. Use of cytological preparations for the intraoperative diagnosis of stereotactically obtained brain biopsies: a 19-year experience and survey of neuropathologists. J Neurosurg 1999;91: 454—8. [8] Steinmeier R, Rachinger J, Kaus M, Ganslandt O, Huk W, Fahlbusch R. Factors influencing the application accuracy of neuronavigation systems. Stereotact Funct Neurosurg 2000;75:188—202. [9] Brommeland T, Hennig R. Mechanical accuracy of a new stereotactic guide. Acta Neurochir (Wien) 2000;142:449—54. [10] Brainard JA, Prayson RA, Barnett GH. Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases. Arch Pathol Lab Med 1997;121:481—4. [11] Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000;92:261—6.
Photodiagnosis for frameless stereotactic biopsy of brain tumor Fumio Yamaguchi MD, PhD a,∗, Hiroshi Takahashi b, Akira Teramoto a a
Department of Neurosurgery, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan b Department of Neurosurgery, Nippon Medical School Musashikosugi Hospital, Kosigi-cho, Nakahara-ku, Kawasaki 211-8533, Japan Available online 3 November 2006 KEYWORDS 5-ALA; Glioma; Malignant lymphoma; Photodynamic diagnosis; Stereotactic biopsy
Summary Stereotactic biopsy is a minimally invasive method of reaching a pathological diagnosis. However, it is not always possible with this method to obtain the tissue samples required for an exact pathological diagnosis. The factors that can make histological diagnoses uncertain are the heterogeneity of tumors and/or brain shifts in the case of small tumors. In this study, we investigated the usefulness of fluorescence in determining the existence of tumor components in obtained tissues. Six patients underwent stereotactic biopsy. 5-Aminolevulinic acid (5-ALA) was administered orally prior to operation. Frameless stereotactic biopsies were performed. The obtained samples were irradiated with 405 nm light and all samples showed red light excitation. Intraoperative rapid pathological diagnosis was made in each case by microscopic examination of frozen section samples. The final pathological diagnoses were of three glioblastomas, one astrocytoma grade 3, and two malignant lymphomas. One case was initially thought to be gliosis on rapid pathological diagnosis, but the final pathological diagnosis reached by examination of a permanent HE stained section was astrocytoma grade 3. Another case, finally diagnosed as malignant lymphoma, was initially diagnosed as infiltration of lymphocytes. The discrepancies between rapid and permanent pathological diagnoses might be caused by the destruction of cells. 5-ALA photodynamic diagnosis is not influenced by the destruction of tissues, simply because it does not depend on the structure of tissues. Stereotactic fluorescence biopsy is very useful in that it enables rapid and exact biopsy and obviates the necessity of waiting for an intraoperative report from a pathologist. © 2006 Elsevier B.V. All rights reserved.
Objective ∗ Corresponding author. Tel.: +81 3 3822 2131; fax: +81 3 5685 0986. E-mail address: [email protected] (F. Yamaguchi).
Frameless biopsy with a neuro-navigator is regularly performed for deep-seated tumors, multiple lesions, and in cases where the removal of a tumor
1572-1000/$ — see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.pdpdt.2006.09.005
72 would lead to deterioration in the patient’s ADL. In this procedure, rapid pathological diagnosis is essential, and this means that tumor tissues sometimes remain undetected in the obtained specimens [1]. The reason tumor components are occasionally not detected on rapid pathological diagnosis may be the destruction of tissues in the freezing process. Photodynamic diagnosis with 5-aminolevulinic acid (5-ALA) has been widely performed for the last several years in many institutes in Japan and Germany to detect brain tumors like gliomas. The procedure is simple [2—4], and postoperative patient care is easier than that following the use of other photosensitizing agents [5]. We have been using 5-ALA fluorescence diagnosis during stereotactic biopsy procedures in a rapid and effective method we call stereotactic fluorescence biopsy.
Patients and methods Between June 2004 and May 2005, six consecutive patients with brain tumors required biopsies. The final pathological diagnoses for these patients
F. Yamaguchi et al. were four gliomas and two malignant lymphomas. Twenty mg/kg body weight of 5-aminolevulinic acid dissolved in 50 ml of 5% glucose solution was administered orally to each patient 1 h prior to the induction of anesthesia. If the patient was unconscious or unable to swallow, the 5-ALA solution was administered through a gastric tube. Frameless stereotactic biopsies were carried out with a neuro-navigator (Stealth Station® , Medtronic SNT, Louisville, CO, USA). The entry point and target point were planned respectively, and a Hennig Instrument GuideTM (Elekta, Stockholm, Sweden) [6] was used to hold the biopsy needle. The needle’s route was determined to avoid eloquent areas and large arteries and veins. A blue laser system (VLDM1, M&M, Tokyo, Japan), which emits 405 ± 1 nm blue light with a power output of 20—60 mW, was used as the light source for fluorescence diagnosis. The obtained specimens were irradiated with 405 nm blue light and observed for red light excitation. Approval of this procedure was obtained from the ethics committee of Nippon Medical School. Informed consent was obtained from the patients and their families.
Figure 1 (A) Gadolinium-enhanced T1-weighted MR images. Gadolinium-enhanced small masses (white arrows) were found in the left frontal lobe. These images suggest malignant glioma. (B) The target point and the entry point were set to avoid important structures (pyramidal tract, visual pathway, language cortices and vessels). (C) Blue-laser light induced the obtained specimen to emit red light, showing that it contained viable tumor cells.
Photodiagnosis for frameless stereotactic biopsy of brain tumor Table 1
1 2 3 4 5 6
73
Summary of cases undergoing fluorescence biopsy
Patient age
Sex
Preoperative diagnosis
Rapid pathology
Red light emission
Final pathology
58 57 78 68 51 71
F M M F M M
GBM GBM GBM Malignant glioma ML ML
GBM GBM AstroG3 Reactive gliosis Lymphocyte ML
+ + + + + +
GBM GBM AstroG3 AstroG3 ML ML
GBM: glioblastoma multiforme, AstroG3: astrocytoma grade3, ML: malignant lymphoma.
Results Representative case (Case #4) A 68-year-old woman developed systemic tonic convulsions. On admission, she exhibited consciousness disturbance and right hemiparesis (MMT2/5). The lesion on MRI was an irregular enhancing mass with surrounding edema in the left frontal lobe (Fig. 1A). These findings suggested that the tumor was highly invasive and not well demarcated. A primary brain tumor, such as a glioma, was suspected in the differential diagnosis. However, a pathological diagnosis was necessary to plan appropriate treatment. We were concerned that total removal of the tumor would lead to postoperative deterioration of her neurological symptoms, so we decided on a stereotactic biopsy followed by adjuvant therapies. The patient underwent a frameless stereotactic biopsy. The target point chosen was the enhanced lesion, and it was confirmed that there were no eloquent areas along the biopsy needle’s trajectory. The needle was registered as a probe on the neuronavigator, and its insertion was monitored on the navigator’s guidance-view (Fig. 1B). Postoperative CT confirmed that the specimen had come from the planned target (Fig. 2). Red light excitement was observed on irradiation with blue light (405 nm) of the obtained specimen (Fig. 1C). The sample was submitted for rapid pathological diagnosis, which revealed glial cell hyperplasty. However, no neoplasm could be confirmed in the tissue, so the diagnosis was gliosis. The final histopathological diagnosis reached by examination of a permanent HE stained section was astrocytoma grade 3.
Other cases The samples obtained from the other patients all showed red luminescence. Case 5, which rapid diagnosis had indicated was lymphocytic invasion, was found to be a malignant lymphoma postoperatively when a permanent preparation was examined. The
Figure 2 The precise biopsy point was reconfirmed by post-operative CT scan.
permanent diagnoses agreed with the rapid pathological diagnoses in the other cases (Table 1).
Discussion Although stereotactic biopsy is a non-invasive method of arriving at a pathological diagnosis, the diagnosis cannot always be relied on [7]. Diagnostic uncertainty can normally be accounted for by heterogeneity of the neoplasm and/or brain shifts causing displacement of the target. The purpose of this study was to determine whether fluorescence diagnosis is useful in confirming the composition of neoplasms in biopsy samples. For a frame-based biopsy, a frame has to be fixed to the patient’s head before image examination,
74 and this can cause both physical and mental discomfort. The advantage to the patient of a frameless biopsy is, therefore, obvious. Another great advantage of performing a biopsy with a neuro-navigator is the discretion it allows in setting the entry point and target point on a monitor, and the ability to confirm the trajectory through the brain structure. The entry point should be set to avoid any eloquent areas, venous sinuses or large vessels so as not to damage them. The trajectory of the biopsy needle should not pass through the pyramidal tract, association fibers connecting the language cortices, or ventricles. Paying attention to these points minimizes the risk of additional neurological damage and intracerebral hemorrhage. Another advantage of biopsy with a neuro-navigator is that as many target points as necessary can be established. If the targeted tumor is heterogeneous, samples from multiple sites are necessary as a matter of course to reach a correct diagnosis and to understand the tumor’s biological activities. Accuracy is an important consideration in comparing frameless with frame-based biopsies. The mean error of a neuronavigator is 2.75 mm [8], and the Hennig Instrument GuideTM used with a navigator has a mean error of 3.8 mm over a 58 mm route [9], as determined by MRI (Viewing Wand, Elekta Instrument AB, Stockholm, Sweden). In most cases, such errors are insignificant. However, carrying out a precise biopsy from the locus planned preoperatively may be difficult when the lesion is very small, especially if there is a large brain shift. In such cases, fluorescence diagnosis can rapidly determine whether the obtained tissue contains tumor components or not, and another target point can be selected when the specimen shows no red light irradiation. The standard method of preparing a specimen for rapid pathological diagnosis is freezing, as it allows quick preparation of the section sample. The disadvantages are that preparation of thin sections and serial sections is difficult, and that the tissue easily disintegrates [7]. And if there is a breakdown of cells and tissue in the frozen section, it is almost impossible to arrive at a correct diagnosis [10]. Once 5-ALA has entered neoplastic cells, however, the level of protoporphyrin IX (PpIX) in the mitochondria increases, as a result of which red light can be excited by blue light even in disintegrated tissue. Because there is little breakdown of cells and tissue, examination of permanent preparations postoperatively is much more likely to lead to a correct diagnosis than examination of frozen sections. This is a great advantage of fluorescence diagnosis. In fact, rapid pathological diagnosis led to incorrect diagnoses in two of our four cases; correct diagnoses were made only after the tissues in
F. Yamaguchi et al. which red color had been confirmed were submitted as permanent preparations for examination later. The tissues submitted for rapid diagnosis presented red fluorescence, and there seem to be limits to the effectiveness of rapid diagnosis based on frozen sections, even when the tissues are the same as those used for permanent preparations. Negative answers from the pathology department on the existence of tumor components in collected tissue lead to repeated biopsies from multiple sites, which in turn lead to more brain tissue being damaged and extended operation time. Such disadvantages can be overcome by our method: the operation can be terminated once fluorescencepositive tissues are obtained. Stereotactic biopsy is especially recommended in the diagnosis of malignant lymphomas [11], and we believe it should become a standard method. On the other hand, the disadvantage of this fluorescence method is its unavailability for tumors which do not take up 5-ALA or produce protoporphyrin IX, resulting in no fluorescence. Our cases were expected to show fluorescence, because preoperative image analysis strongly suggested the diagnoses eventually reached, and malignant gliomas and malignant lymphomas are known to show strong fluorescence. However, there may be false-negative neoplasms, which do not show fluorescence. Kaneko reported that 25 samples out of 61 malignant glioma samples (41%) did not show fluorescence [2]. Therefore we must be very careful for false-negative cases. In addition, macroscopical fluorescence is not expected in low-grade gliomas or inflamed tissues, so this method will be unsuitable for diagnosing them [2]. Moreover histological diagnosis cannot be made by fluorescence diagnosis. Needless to say, fluorescence diagnosis cannot distinguish between glioblastoma, anaplastic astrocytoma and malignancy lymphoma and histopathological diagnosis gives accurate and exact histological diagnosis. When the fluorescence is weak, confirmation of PpIX fluorescence by spectroscopy is an option; however further analysis is necessary to determine whether tissues with weak fluorescence are actually the tumors we expect. The development of new tissue-labeling substances taken in by the neoplasms of low-grade malignancies can be expected.
Conclusion Stereotactic fluorescence biopsy is a safe and useful method. Fluorescence diagnosis, especially with 5-ALA, is a method with few complications that enables quick and exact biopsies.
Photodiagnosis for frameless stereotactic biopsy of brain tumor
References [1] Hall WA. The safety and efficacy of stereotactic biopsy for intracranial lesions. Cancer 1998;82:1749—55. [2] Kaneko S. Intraoperative photodynamic diagnosis of human glioma using ALA induced protoporphyrin IX. No Shinkei Geka 2001;29:1019—31 (in Japanese). [3] Stummer W, Stocker S, Wagner S, et al. Intraoperative detection of malignant gliomas by 5-aminolevulinic acidinduced porphyrin fluorescence. Neurosurgery 1998;42: 518—26. [4] Stummer W, Novotny A, Stepp H, Goetz C, Bise K, Reulen HJ. Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. J Neurosurg 2000;93:1003—13. [5] Webber J, Kessel D, Fromm D. Side effects and photosensitization of human tissues after aminolevulinic acid. J Surg Res 1997;68:31—7. [6] Brommeland T, Hennig R. A new procedure for frameless computer navigated stereotaxy. Acta Neurochir (Wien) 2000;142:443—7.
75
[7] Firlik KS, Martinez AJ, Lunsford LD. Use of cytological preparations for the intraoperative diagnosis of stereotactically obtained brain biopsies: a 19-year experience and survey of neuropathologists. J Neurosurg 1999;91: 454—8. [8] Steinmeier R, Rachinger J, Kaus M, Ganslandt O, Huk W, Fahlbusch R. Factors influencing the application accuracy of neuronavigation systems. Stereotact Funct Neurosurg 2000;75:188—202. [9] Brommeland T, Hennig R. Mechanical accuracy of a new stereotactic guide. Acta Neurochir (Wien) 2000;142:449—54. [10] Brainard JA, Prayson RA, Barnett GH. Frozen section evaluation of stereotactic brain biopsies: diagnostic yield at the stereotactic target position in 188 cases. Arch Pathol Lab Med 1997;121:481—4. [11] Bataille B, Delwail V, Menet E, et al. Primary intracerebral malignant lymphoma: report of 248 cases. J Neurosurg 2000;92:261—6.
![[Frameless stereotactic biopsy: diagnostic yield and complications].](/assets/img/hold.png)
