The use of fluorescein sodium in the biopsy and gross-total resection of a tectal plate glioma

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Intravenous administration of fluorescein sodium fluoresces glioma burden tissue and can be visualized using the surgical microscope with a specialized filter. Intraoperative guidance afforded through the use of fluorescein may enhance the fidelity of tissue sampling, and increase the ability to accomplish complete resection of tectal lesions. In this report the authors present the case of a 19-year-old man with a tectal anaplastic pilocytic astrocytoma in which the use of fluorescein sodium and a Zeiss Pentero surgical microscope equipped with a yellow 560 filter enabled safe complete resection. In conjunction with neurosurgical navigation, added intraoperative guidance provided by fluorescein may be beneficial in the resection of brainstem gliomas.

Intravenous administration of fluorescein sodium fluoresces glioma burden tissue and can be visualized using the surgical microscope with a specialized filter. Intraoperative guidance afforded through the use of fluorescein may enhance the fidelity of tissue sampling, and increase the ability to accomplish complete resection of tectal lesions. In this report the authors present the case of a 19-year-old man with a tectal anaplastic pilocytic astrocytoma in which the use of fluorescein sodium and a Zeiss Pentero surgical microscope equipped with a yellow 560 filter enabled safe complete resection. In conjunction with neurosurgical navigation, added intraoperative guidance provided by fluorescein may be beneficial in the resection of brainstem gliomas.

The quadrigeminal plate, also known as the tectum, is embryonically derived from the alar plate of the neural tube and contains auditory and visual reflex pathways.12 The position of the superior colliculi, inferior colliculi, and the close proximity of the cerebral aqueduct leave this anatomical region susceptible to lesional disruption of visual and auditory pathways as well as interruption of normal CSF flow.12 Patients harboring lesions within the tectal plate commonly present with obstructive hydrocephalus secondary to occlusion of the cerebral aqueduct. Additional common symptoms include headaches, nausea, vomiting, visual abnormalities such as oculomotor palsy and Parinaud syndrome, and imbalance.8

Lesions occupying the tectal plate include pineal-derived lesions, benign hamartomas, low-grade astrocytomas, and, rarely, anaplastic astrocytomas. Tectal plate gliomas comprise approximately 5%8 of all pediatric brainstem gliomas and are represented by pilocytic astrocytoma (36%), fibrillary astrocytoma (21%), oligoastrocytoma (14%), ganglioglioma (7%), and high-grade astrocytoma (7%).21 Management strategies for tectal plate lesions in the pediatric population vary by center and may include tissue diagnosis for contrast-enhancing lesions, through a stereotactic biopsy, endoscopic biopsy, or an open biopsy and resection. Gross-total resection is reserved for tumors that present to the surface of the brainstem and those in which a clear plane can safely be established between the lesion and surrounding eloquent tissue.13

Surgical approaches to the tectum are similar to described techniques for pineal region lesions, and include suboccipital-transtentorial, interhemispheric transtentorial, and supracerebellar-infratentorial approaches.12–14 In addition to intraoperative neuronavigation, adjuvant use of fluorescein sodium may increase the fidelity of tissue sampling and aid in the resection of tectal lesions by distinguishing the tumor from the surrounding eloquent tissue in real time.

Fluorescein sodium is a highly fluorescent molecule that is currently FDA approved for use in ophthalmology, and has been reported to assist in the resection of high-grade gliomas.1,2,11,17 Fluorescein extravasates into areas of blood-brain barrier breakdown representative of tumor tissue. The use of fluorescein in glioblastoma resection has been associated with improved rates of tumor resection.2,9,19 Intravenous administration of fluorescein has been demonstrated to be safe, although allergic anaphylactic reactions have been reported.3,4,6 The pharmacokinetics of fluorescein are favorable for intraoperative use, with rapid distribution to tissues within 10 minutes, a plasma half-life of 23.5 minutes, and overall systemic clearance of 500 mg of fluorescein in 2 to 3 days (http://ecatalog.alcon.com/PI/FluoresciteInjection_us_en.pdf).

After intravenous administration, fluorescein sodium fluorescence can be visualized utilizing a surgical microscope equipped with a fluorescent filter system. Specifically, a Zeiss Pentero 900 surgical microscope (Carl Zeiss) outfitted with a yellow 560 long-pass through filter achieves visualization of yellow-green fluorescein-stained tissue in the setting of a normal-appearing background, and allows safe fluorescein-guided microsurgery.

Accordingly, the application of fluorescein sodium to resection of contrast-enhancing lesions in the quadrigeminal plate may confirm the surgical site, confirm acquisition of pathologic tissue, and guide resection. In this paper we report the case of a patient who received 10% fluorescein sodium (Alcon Laboratories) at 3 mg/kg intravenously prior to resection of a contrast-enhancing lesion located within the tectal plate.

Case Report

History and Presentation

A 19-year-old man with a 2-month history of intermittent headaches, double vision, nausea, and vomiting initially presented to his primary care physician, where MRI revealed a 1.7 cm × 1.9–cm contrast-enhancing mass of the midbrain and associated hydrocephalus (Fig. 1). Examination of the patient revealed orientation to name, date, and place, without additional focal neurological deficits. Given the contrast enhancement of the lesion on MRI and the concern for a possible high-grade glioma, a decision was made to operate rather than pursue a more conservative management course.

FIG. 1.
FIG. 1.

Preoperative MRI illustrating a 1.7 cm × 1.9–cm mass located in the tectal plate. Axial (A) and sagittal (B) T1-weighted postcontrast images are shown.

Operation

The patient underwent endoscopic third ventriculostomy for treatment of hydrocephalus 1 week prior to the planned resection of the tectal lesion. Approximately 1 week later, the patient was consented for intravenous administration of 10% fluorescein sodium prior to surgery via an institutional review board–approved protocol. The patient was placed into the right lateral decubitus position for a right-sided occipital transtentorial approach. Fluorescein sodium (10%) was intravenously administered to the patient at a dose of 3 mg/kg at the time of incision.

A right parietooccipital craniotomy and occipital transtentorial corridor exposed the posterior superior brainstem. The superior colliculi were moderately swollen and avascular. A midline incision was made at the geometrical center of the lesion between the superior colliculi. Subsequently, the yellow 560 filter was employed and the lesion was found to be highly fluorescent (Fig. 2A and B). Resection of the mass was achieved with neurosurgical navigation in conjunction with intraoperative fluorescent guidance (Fig. 2C and D). Residual fluorescein-stained tissue allowed for verification of complete resection, and no visible fluorescent tissue remained within the resection cavity (Fig. 2D). Total operative time was 4 hours 3 minutes, and was without complication.

FIG. 2.
FIG. 2.

Intraoperative images obtained using a Zeiss Pentero 900 microscope equipped with a yellow 560 filter. Microsurgical photograph of the tectal lesion under white light (A) and with the yellow 560 filter engaged (B) from initial stages of tumor resection. A microsurgical mirror was used to examine the resection cavity for residual tissue. Residual tissue located in the proximal borders of the resection cavity was identified and removed (C). Final inspection of the resection cavity indicated no residual tumor tissue (D). Figure is available in color online only.

Postoperative Course

Postoperatively, the patient was found to have symptoms consistent with Parinaud syndrome and bilateral ophthalmoplegia. Throughout his hospital course, his ocular symptoms resolved significantly, and he was discharged to rehabilitation on postoperative Day 10 with a moderate upgaze palsy. Three months postoperatively, the patient continues to demonstrate improvement of his Parinaud syndrome compared with his postsurgical baseline. Postoperative MRI of the brain demonstrated gross-total resection of the lesion in the immediate postoperative period (Fig. 3) as well as on surveillance MRI 2 months later. Consequently, a clinical decision was made to conservatively monitor the patient without treatment with chemotherapy and/or radiation.

FIG. 3.
FIG. 3.

Postoperative MRI demonstrating complete resection of the tectal lesion. Axial (A) and sagittal (B) T1-weighted postcontrast images are shown.

Pathological Examination

Formalin-fixed, paraffin-embedded sections acquired from this patient illustrate the pathological diagnosis of an anaplastic pilocytic astrocytoma. The mitotic activity was globally increased, with multiple foci having a range of 4–7 mitotic figures per 10 high-power fields, as well as several microscopic fields containing multiple mitotic figures (as high as 5 per high-power field). Increased single-cell necrosis was also noted. Ki 67 labeling was variably increased but was focally measured as high as 17%. Additionally, large fragments of global tumor necrosis and florid glomeruloid vascular proliferations were observed (Fig. 4).

FIG. 4.
FIG. 4.

Formalin-fixed, paraffin-embedded sections demonstrate an anaplastic pilocytic astrocytoma. Increased mitotic activity, tumor necrosis, and glomeruloid vascular proliferations are globally noted. Original magnification ×40. Figure is available in color online only.

Discussion

Fluorescein Sodium: Safety and Application

Recent evidence suggests the safe application of fluorescein sodium in malignant glioma and can be applied to lesions of the tectal plate, where safe entry and identification of the gliotic plane are necessary.15 Administration of 10% fluorescein sodium at a dose of 3 mg/kg after the induction of anesthesia, but prior to surgical incision, was not associated with adverse events and provided adequate fluorescence of the lesion without associated staining of the surrounding normal parenchyma. Furthermore, fluorescein-stained tissue was consistent with neurosurgical navigation, and provided the surgical team with intraoperative microsurgical guidance during tumor resection. This minimized normal tissue manipulation, and facilitated microsurgical dissection of the lesion from the surrounding parenchyma.

With the Zeiss yellow 560 filter, it was relatively easy to visualize the discretely fluorescein tumor tissue. Fluorescein staining was found by the operating surgeons to be advantageous during the course of the surgery, and provided intraoperative identification of residual tumor tissue. Utilizing a microsurgical mirror (Fig. 2C), identification of residual fluorescent tissue within the resection cavity facilitated complete resection and was verified on postoperative MRI (Fig. 3).

Anaplastic Pilocytic Astrocytoma

Pilocytic astrocytomas are generally regarded as benign tumors (WHO Grade I), usually occurring in pediatric and young adult populations. Typically, these tumors are located within the posterior fossa, and treatment ranges from radiographic surveillance to resection. Although generally considered an indolent disease, aggressive histopathological features, subtotal resection, and brainstem lesions are linked to worse prognosis.5,18,20,22

Histopathological diagnosis of pilocytic astrocytoma is important, as identification of anaplastic features may influence treatment algorithms.10,20,22 Although relatively rare, the presence of malignant features within pilocytic astrocytomas is associated with a more aggressive disease course. Anaplastic pilocytic astrocytoma differs from typical pilocytic astrocytoma and these tumors exhibit increased mitotic figures, necrosis, and endothelial proliferations.7,10,23 Presence of these features is associated with a decrease in overall and progression-free survival when compared with typical pilocytic astrocytoma.16,22,23 Given the rarity of this tumor, limited research exists defining the postoperative treatment of anaplastic pilocytic astrocytoma, although reports suggest response to early temozolomide chemotherapy.16

In patients with a brainstem tumor, safe maximal resection may prove beneficial in the overall prognosis of patients.20 Adjuvant use of fluorescein may increase surgical identification of tumor tissue for histopathological analysis and impact the ability to achieve maximal safe resection.

Our clinical case presentation illustrates the safety and utility of fluorescein sodium in the identification and resection of quadrigeminal lesions. In combination with neurosurgical navigation, the additional intraoperative guidance afforded by fluorescein may ultimately impact patient treatment and prognosis by facilitating the more specific resection of pathological tissue in such a highly eloquent area. Additional studies are warranted to fully investigate the utility of fluorescein sodium in the resection of brainstem lesions.

Author Contributions

Conception and design: Ung, Kellner. Acquisition of data: Ung. Analysis and interpretation of data: Kellner. Drafting the article: Ung, Kellner, Wang, Faust. Critically revising the article: Ung, Kellner, Neira, Wang, Canoll, Bruce. Reviewed submitted version of manuscript: Wang, D’Amico, Faust, Canoll, Feldstein, Bruce. Approved the final version of the manuscript on behalf of all authors: Ung. Study supervision: Ung, Bruce.

References

  • 1

    Acerbi FBroggi MEoli MAnghileri ECavallo CBoffano C: Is fluorescein-guided technique able to help in resection of high-grade gliomas?. Neurosurg Focus 36:2E52014

    • Search Google Scholar
    • Export Citation
  • 2

    Acerbi FBroggi MEoli MAnghileri ECuppini LPollo B: Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases. Acta Neurochir (Wien) 155:127712862013

    • Search Google Scholar
    • Export Citation
  • 3

    Balbino MSilva GCorreia GCTP: Anaphylaxis with convulsions following intravenous fluorescein angiography at an outpatient clinic. Einstein (Sao Paulo) 10:3743762012

    • Search Google Scholar
    • Export Citation
  • 4

    Bearelly SRao SFekrat S: Anaphylaxis following intravenous fluorescein angiography in a vitreoretinal clinic: report of 4 cases. Can J Ophthalmol 44:4444452009

    • Search Google Scholar
    • Export Citation
  • 5

    Cyrine SSonia ZMounir TBadderedine SKalthoum THedi K: Pilocytic astrocytoma: a retrospective study of 32 cases. Clin Neurol Neurosurg 115:122012252013

    • Search Google Scholar
    • Export Citation
  • 6

    Dilek OIhsan ATulay H: Anaphylactic reaction after fluorescein sodium administration during intracranial surgery. J Clin Neurosci 18:4304312011

    • Search Google Scholar
    • Export Citation
  • 7

    Dirks PBJay VBecker LEDrake JMHumphreys RPHoffman HJ: Development of anaplastic changes in low-grade astrocytomas of childhood. Neurosurgery 34:68781994

    • Search Google Scholar
    • Export Citation
  • 8

    Griessenauer CJRizk EMiller JHHendrix PTubbs RSDias MS: Pediatric tectal plate gliomas: clinical and radiological progression, MR imaging characteristics, and management of hydrocephalus. J Neurosurg Pediatr 13:13202014

    • Search Google Scholar
    • Export Citation
  • 9

    Koc KAnik ICabuk BCeylan S: Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. Br J Neurosurg 22:991032008

    • Search Google Scholar
    • Export Citation
  • 10

    Krieger MDGonzalez-Gomez ILevy MLMcComb JG: Recurrence patterns and anaplastic change in a long-term study of pilocytic astrocytomas. Pediatr Neurosurg 27:1111997

    • Search Google Scholar
    • Export Citation
  • 11

    Kuroiwa TKajimoto YOhta T: Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report. Surg Neurol 50:41491998

    • Search Google Scholar
    • Export Citation
  • 12

    Lapras CBognar LTurjman FVillanyi EMottolese CFischer C: Tectal plate gliomas. Part I: Microsurgery of the tectal plate gliomas. Acta Neurochir (Wien) 126:76831994

    • Search Google Scholar
    • Export Citation
  • 13

    Lázaro BCRLandeiro JA: Tectal plate tumors. Arq Neuropsiquiatr 64:4324362006

  • 14

    McLaughlin NMartin NA: The occipital interhemispheric transtentorial approach for superior vermian, superomedian cerebellar, and tectal arteriovenous malformations: advantages, limitations, and alternatives. World Neurosurg 82:4094162014

    • Search Google Scholar
    • Export Citation
  • 15

    Miyamoto SMikuni NYamada KTakahashi JAHashimoto N: Radical resection for intrinsic midbrain pilocytic astrocytoma: report of two cases. Acta Neurochir (Wien) 147:93972005

    • Search Google Scholar
    • Export Citation
  • 16

    Rodriguez FJScheithauer BWBurger PCJenkins SGiannini C: Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol 34:1471602010

    • Search Google Scholar
    • Export Citation
  • 17

    Schebesch KMProescholdt MHöhne JHohenberger CHansen ERiemenschneider MJ: Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:6936992013

    • Search Google Scholar
    • Export Citation
  • 18

    Shibahara IKawaguchi TKanamori MYonezawa STakazawa HAsano K: Pilocytic astrocytoma with histological malignant features without previous radiation therapy-case report. Neurol Med Chir (Tokyo) 51:1441472011

    • Search Google Scholar
    • Export Citation
  • 19

    Shinoda JYano HYoshimura SOkumura AKaku YIwama T: Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note J Neurosurg 99:5976032003

    • Search Google Scholar
    • Export Citation
  • 20

    Stüer CVilz BMajores MBecker ASchramm JSimon M: Frequent recurrence and progression in pilocytic astrocytoma in adults. Cancer 110:279928082007

    • Search Google Scholar
    • Export Citation
  • 21

    Ternier JWray APuget SBodaert NZerah MSainte-Rose C: Tectal plate lesions in children. J Neurosurg 104:6 Suppl3693762006

  • 22

    Tibbetts KMEmnett RJGao FPerry AGutmann DHLeonard JR: Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol 117:6576652009

    • Search Google Scholar
    • Export Citation
  • 23

    Tomlinson FHScheithauer BWHayostek CJParisi JEMeyer FBShaw EG: The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study. J Child Neurol 9:3013101994

    • Search Google Scholar
    • Export Citation

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Article Information

Contributor Notes

Correspondence Timothy H. Ung, Irving Cancer Research Center, Columbia University Medical Center, 1130 St. Nicholas Ave., #10-01, New York, NY 10032. email: tu2142@columbia.edu.INCLUDE WHEN CITING Published online September 25, 2015; DOI: 10.3171/2015.5.PEDS15142.Disclosure The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Headings
Figures
  • View in gallery

    Preoperative MRI illustrating a 1.7 cm × 1.9–cm mass located in the tectal plate. Axial (A) and sagittal (B) T1-weighted postcontrast images are shown.

  • View in gallery

    Intraoperative images obtained using a Zeiss Pentero 900 microscope equipped with a yellow 560 filter. Microsurgical photograph of the tectal lesion under white light (A) and with the yellow 560 filter engaged (B) from initial stages of tumor resection. A microsurgical mirror was used to examine the resection cavity for residual tissue. Residual tissue located in the proximal borders of the resection cavity was identified and removed (C). Final inspection of the resection cavity indicated no residual tumor tissue (D). Figure is available in color online only.

  • View in gallery

    Postoperative MRI demonstrating complete resection of the tectal lesion. Axial (A) and sagittal (B) T1-weighted postcontrast images are shown.

  • View in gallery

    Formalin-fixed, paraffin-embedded sections demonstrate an anaplastic pilocytic astrocytoma. Increased mitotic activity, tumor necrosis, and glomeruloid vascular proliferations are globally noted. Original magnification ×40. Figure is available in color online only.

References
  • 1

    Acerbi FBroggi MEoli MAnghileri ECavallo CBoffano C: Is fluorescein-guided technique able to help in resection of high-grade gliomas?. Neurosurg Focus 36:2E52014

    • Search Google Scholar
    • Export Citation
  • 2

    Acerbi FBroggi MEoli MAnghileri ECuppini LPollo B: Fluorescein-guided surgery for grade IV gliomas with a dedicated filter on the surgical microscope: preliminary results in 12 cases. Acta Neurochir (Wien) 155:127712862013

    • Search Google Scholar
    • Export Citation
  • 3

    Balbino MSilva GCorreia GCTP: Anaphylaxis with convulsions following intravenous fluorescein angiography at an outpatient clinic. Einstein (Sao Paulo) 10:3743762012

    • Search Google Scholar
    • Export Citation
  • 4

    Bearelly SRao SFekrat S: Anaphylaxis following intravenous fluorescein angiography in a vitreoretinal clinic: report of 4 cases. Can J Ophthalmol 44:4444452009

    • Search Google Scholar
    • Export Citation
  • 5

    Cyrine SSonia ZMounir TBadderedine SKalthoum THedi K: Pilocytic astrocytoma: a retrospective study of 32 cases. Clin Neurol Neurosurg 115:122012252013

    • Search Google Scholar
    • Export Citation
  • 6

    Dilek OIhsan ATulay H: Anaphylactic reaction after fluorescein sodium administration during intracranial surgery. J Clin Neurosci 18:4304312011

    • Search Google Scholar
    • Export Citation
  • 7

    Dirks PBJay VBecker LEDrake JMHumphreys RPHoffman HJ: Development of anaplastic changes in low-grade astrocytomas of childhood. Neurosurgery 34:68781994

    • Search Google Scholar
    • Export Citation
  • 8

    Griessenauer CJRizk EMiller JHHendrix PTubbs RSDias MS: Pediatric tectal plate gliomas: clinical and radiological progression, MR imaging characteristics, and management of hydrocephalus. J Neurosurg Pediatr 13:13202014

    • Search Google Scholar
    • Export Citation
  • 9

    Koc KAnik ICabuk BCeylan S: Fluorescein sodium-guided surgery in glioblastoma multiforme: a prospective evaluation. Br J Neurosurg 22:991032008

    • Search Google Scholar
    • Export Citation
  • 10

    Krieger MDGonzalez-Gomez ILevy MLMcComb JG: Recurrence patterns and anaplastic change in a long-term study of pilocytic astrocytomas. Pediatr Neurosurg 27:1111997

    • Search Google Scholar
    • Export Citation
  • 11

    Kuroiwa TKajimoto YOhta T: Development of a fluorescein operative microscope for use during malignant glioma surgery: a technical note and preliminary report. Surg Neurol 50:41491998

    • Search Google Scholar
    • Export Citation
  • 12

    Lapras CBognar LTurjman FVillanyi EMottolese CFischer C: Tectal plate gliomas. Part I: Microsurgery of the tectal plate gliomas. Acta Neurochir (Wien) 126:76831994

    • Search Google Scholar
    • Export Citation
  • 13

    Lázaro BCRLandeiro JA: Tectal plate tumors. Arq Neuropsiquiatr 64:4324362006

  • 14

    McLaughlin NMartin NA: The occipital interhemispheric transtentorial approach for superior vermian, superomedian cerebellar, and tectal arteriovenous malformations: advantages, limitations, and alternatives. World Neurosurg 82:4094162014

    • Search Google Scholar
    • Export Citation
  • 15

    Miyamoto SMikuni NYamada KTakahashi JAHashimoto N: Radical resection for intrinsic midbrain pilocytic astrocytoma: report of two cases. Acta Neurochir (Wien) 147:93972005

    • Search Google Scholar
    • Export Citation
  • 16

    Rodriguez FJScheithauer BWBurger PCJenkins SGiannini C: Anaplasia in pilocytic astrocytoma predicts aggressive behavior. Am J Surg Pathol 34:1471602010

    • Search Google Scholar
    • Export Citation
  • 17

    Schebesch KMProescholdt MHöhne JHohenberger CHansen ERiemenschneider MJ: Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery—a feasibility study. Acta Neurochir (Wien) 155:6936992013

    • Search Google Scholar
    • Export Citation
  • 18

    Shibahara IKawaguchi TKanamori MYonezawa STakazawa HAsano K: Pilocytic astrocytoma with histological malignant features without previous radiation therapy-case report. Neurol Med Chir (Tokyo) 51:1441472011

    • Search Google Scholar
    • Export Citation
  • 19

    Shinoda JYano HYoshimura SOkumura AKaku YIwama T: Fluorescence-guided resection of glioblastoma multiforme by using high-dose fluorescein sodium. Technical note J Neurosurg 99:5976032003

    • Search Google Scholar
    • Export Citation
  • 20

    Stüer CVilz BMajores MBecker ASchramm JSimon M: Frequent recurrence and progression in pilocytic astrocytoma in adults. Cancer 110:279928082007

    • Search Google Scholar
    • Export Citation
  • 21

    Ternier JWray APuget SBodaert NZerah MSainte-Rose C: Tectal plate lesions in children. J Neurosurg 104:6 Suppl3693762006

  • 22

    Tibbetts KMEmnett RJGao FPerry AGutmann DHLeonard JR: Histopathologic predictors of pilocytic astrocytoma event-free survival. Acta Neuropathol 117:6576652009

    • Search Google Scholar
    • Export Citation
  • 23

    Tomlinson FHScheithauer BWHayostek CJParisi JEMeyer FBShaw EG: The significance of atypia and histologic malignancy in pilocytic astrocytoma of the cerebellum: a clinicopathologic and flow cytometric study. J Child Neurol 9:3013101994

    • Search Google Scholar
    • Export Citation
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