J Neurooncol (2008) 89:49–50 DOI 10.1007/s11060-008-9584-7
IMAGES IN NEURO-ONCOLOGY
Low grade astrocytoma presenting with visual loss Morris D. Groves Æ Ruth L. Katz
Received: 19 February 2008 / Accepted: 28 March 2008 / Published online: 9 April 2008 Ó Springer Science+Business Media, LLC. 2008
An 18 year old man presented with 1 week of monocular blindness. Examination revealed no light perception from the left eye, a dilated left pupil and bilateral papilledema. Brain MRI revealed a non-enhancing left thalamic mass (Fig. 1a) and contrast enhancement of the optic nerves (Fig. 1b, arrows), as well as MRI contrast enhancement along the thoracic cord, conus medullaris and cauda equina, suggestive of tumor dissemination in these regions. CSF opening pressure was 44 cm H2O, protein was 896 mg/dl, contained 11 WBCs, and tumor cells. Biopsy of the thalamic mass revealed a grade II astrocytoma. Tumor cells (Fig. 1c) from the CSF and the brain revealed EGFR polysomy. GFAP positive tumor cells also revealed polysomy for PI3kinase and pTEN. Because of the tumor cells found floating in the CSF and MRI evidence of enhancement along the cord and cauda equina, the patient was treated with craniospinal irradiation (CSI). Thirty-six Gray (Gy) was delivered to the brain and spine, followed by an additional boost (final dose 54 Gy over 30 fractions) to the left thalamic tumor, using intensity modulated radiotherapy. Consideration was given to combining temozolomide chemotherapy with the CSI, but because of a concern for possible significant myelosuppression from such a large radiation field along with the chemotherapy, CSI was administered alone. In preparation for possible intrathecal chemotherapy, a ventricular reservoir was placed.
Even though the patient is clinically stable, his CSF pressures have remained high ([30 cm H2O) as measured through the reservoir. He continues to have CSF removal on a weekly or twice weekly basis for pressure relief. Because of the persistence of tumor cells floating in the CSF, temozolomide chemotherapy at a dose of 100 mg/ M2/day, 7 days on 7 days off, was initiated 11 weeks after the completion of radiation. This therapy is ongoing. The incidence of CSF dissemination in high grade gliomas can be as high as 27% at autopsy [1], while diagnosis before death can be as low as 2% [2]. In low grade gliomas, the incidence of CSF dissemination of tumor cells at the time of tumor diagnosis is 5% [3]. Amplification of the EGFR gene is not usually associated with grade II astrocytoma, but can be seen in up to 10% of anaplastic astrocytomas and 36% of primary glioblastomas [4]. Common genetic changes in grade II astrocytomas include p53 mutations, chromosome 7q, 5p, 9 and 19p gains, and losses on 19q, 1p, Xp. Due to the small sample size of the biopsy, it is possible that the true grade of this patient’s tumor might have been grade III or IV. If this tumor is actually a grade II astrocytoma, the abnormalities of EGFR, pTEN and PI3kinase may have contributed to it’s behavior. Acknowledgment We gratefully acknowledge Ms. Abha Khanna, who performed the FISH and made the PI3kinase probe.
References M. D. Groves (&) R. L. Katz The University of Texas MD Anderson Cancer Center, Unit 431, 1515 Holcombe Boulevard, Houston, TX 77030, USA e-mail:
[email protected] R. L. Katz e-mail:
[email protected]
1. Onda K, Tanaka R, Takahashi H, Takeda N, Ikuta F (1989) Cerebral glioblastoma with cerebrospinal fluid dissemination: a clinicopathological study of 14 cases examined by complete autopsy. Neurosurgery 25:533–540 2. Vertosick FT, Selker RG (1990) Brain stem and spinal metastases of supratentorial glioblastoma multiforme: a clinical series. Neurosurgery 27:516–521
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50 Fig. 1 Panel A: Axial, T2 FLAIR (fluid-attenuated inversion recovery) MRI brain scan demonstrating high signal mass in left posterior thalamus (mass was non-enhancing on contrast-enhanced scans). Panel B: Coronal T1 contrastenhanced MRI brain scan demonstrating contrast enhancement of both optic nerves (arrows). Panel C: Photomicrographs of tumor cells using fluorescence in-situ hybridization (FISH) demonstrating EGFR polysomy (tumor tissue and CSF), and PTEN and PI3K polysomy (tumor tissue)
J Neurooncol (2008) 89:49–50
A
C
B
Tumor
CSF
EGFR (7p12) FISH: Polysomy (4-4) EGFR (red) & centromeric 7 (green) in tumor cells stained with GFAP (arrow) and atypical cells in CSF (arrow)
PTEN (10q23.3) FISH: Polysomy (4-4) PTEN (red) & centromeric 10 (green) in GFAP positive cells (arrow)
PIK3CA (3q26) FISH: Polysomy (4-4) centromeric 3 (red) & PIK3CA (green) in tumor cell (arrow)
3. Gajjar A, Bhargava R, Jenkins JJ, Heideman R, Sanford RA, Langston JW, Walter AW, Kuttesch JF, Muhlbauer M, Kun LE (1995) Low-grade astrocytoma with neuraxis dissemination at diagnosis. J Neurosurg 83:67–71
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4. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007) WHO classification of tumours of the central nervous system. IARC, Lyon
