Surgery of Spinal Cord Pilocytic Astrocytoma Complicated by Leptomeningeal Dissemination to the Brain and Spine and Rapid Progression

Home , Pilocytic astrocytoma, Spinal tumor

Formosan Journal of Surgery (2013) 46,65e69

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CASE REPORT Surgery of spinal cord pilocytic astrocytoma complicated by leptomeningeal dissemination to the brain and spine and rapid progression

Yu-Lin Chou a,b, Joon-Khim Loh a,b,*, Shiuh-Lin Hwang a,b a Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan b Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Received 10 June 2012; received in revised form 29 August 2012; accepted 14 September 2012 Available online 6 April 2013

KEYWORDS Summary Pilocytic astrocytoma (PCA) is a common benign astrocytic tumor in children that children; usually arises in the cerebellum, brainstem, hypothalamic region, or optic pathways. It can leptomeningeal also arise in the spinal cord as an intradural intramedullary PCA. In rare cases, it presents with dissemination; leptomeningeal dissemination, which leads to a poor clinical outcome. We present a rare case pilocytic astrocytoma of spinal cord pilocytic astrocytoma with leptomeningeal dissemination to the brain and spine with rapid progression. We present a 13-year-old girl with progressive weakness of her right arm. An intramedullary hypervascular neurogenic tumor at the C3eC6 level was identified by magnetic resonance imaging (MRI) and surgical excision was performed. PCA was proven by pathology. The tumor recurred 3 months later and an intramedullary polycystic astrocytoma at the C1eT1 level was confirmed by MRI. Total tumor resection was performed and pathological characteristics again confirmed PCA. However, diplopia with blurred vision was noted 1 month after the last surgery, which was accompanied by signs of increased intracranial pres- sure (IICP). MRI indicated leptomeningeal enhancement in the brain and tumor seeding along the spinal cord. Chemotherapy and radiotherapy were administered, but the clinical course rapidly deteriorated and the patient died of respiratory distress. Although the prognosis for low-grade astrocytomas is good in most reported studies, this case showed leptomeningeal dissemination with a rapid course that resulted in death. A fatal outcome might be anticipated when encountering difficult intramedullary spinal cord lesions, as in our case. Copyright ª 2013, Taiwan Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.

* Corresponding author. Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung 80708, Taiwan. E-mail address: saﬁ[email protected] (J.-K. Loh).

1. Introduction

Pilocytic astrocytoma (PCA) is a common astrocytic tumor in children that most commonly arises in the cerebellum, brainstem, hypothalamic region, or optic pathways.1 It can also arise from the spinal cord, which accounts for 9% of PCA cases.2 It is usually benign with a favorable outcome, although in rare cases it presents with leptomeningeal dissemination, which leads to a poor clinical outcome.3 We present a case of spinal cord intradural intramedullary PCA with leptomeningeal dissemination to the brain and spine with rapid progression.

2. Case report

A 13-year-old girl presented with progressive weakness of Figure 2 Histology of the spinal cord tumor showing a her right arm that first occurred over 1 month before her biphasic pattern with compact bipolar cells and loose-textured visit. An intramedullary hypervascular neurogenic tumor at multipolar cells with microcysts and granular bodies (hema- the C3eC6 level was identified by magnetic resonance im- toxylin and eosin stain, 40Â). aging (MRI) (Fig. 1A). Surgical resection of the tumor and an intraoperative frozen section revealed a high-grade astrocytoma; thus, a C3eC6 laminectomy and subtotal tumor Three months later, progressive muscle weakness in the resection were performed. However, the permanent pa- patient’s right arm recurred. MRI revealed enlargement of thology report was a WHO grade I PCA that exhibited a the intramedullary astrocytoma at the C1eT1 level biphasic pattern with compact bipolar cells and loose- (Fig. 1B). A C3eT1 laminectomy and total resection of the textured multipolar cells with microcysts and granular spinal tumor were performed. Piecemeal resection of the bodies. An immunohistochemical study showed that the tumor was carried out until a clean surgical field was ob- tumor cells were GFAP-positive and EMA-negative. The Ki- tained under a microscope at the end of the procedure, and 67 labeling index was <5% (Fig. 2). a clean postoperative MRI was recorded (Fig. 1C). The

Figure 1 Spinal MRI (sagittal T1-weighted MRI with gadolinium contrast) showing (A) preoperative intramedullary tumor, (B) recurrence of the intramedullary astrocytoma from the cervical to the thoracic level, (C) total removal of the tumor after the second surgery, (D) leptomeningeal enhancement at the cervical level extended to the cauda equina, and (E) tumor seeding in the central canal with related syringomyelia at C2eC6 with (F) worsening of leptomeningeal metastases at the upper T spine level. Spinal cord PCA with brain & spine dissemination 67 pathology report was still PCA and radiotherapy was carried leptomeningeal metastases at the upper T spine level out because of the rapid recurrence. (Fig. 1E and F). Only 1 month after the last surgery, the patient expe- Because of the poor response, the chemotherapeutic rienced diplopia with blurred vision, which was accompa- agent was changed to temozolomide, and then to cyclo- nied by dizziness, headache, and poor appetite. MRI of the phosphamide and mesna. Disturbance of consciousness brain showed some leptomeningeal enhancement around occurred with frequent seizures after 1 month of treat- the brain stem and suspicion of seeding (Fig. 3A and B). ment. A repeat brain MRI showed multiple enlarged nodules Spinal MRI showed that leptomeningeal enhancement at in the cerebellum, the left medial temporal lobe, the right the cervical level had extended to the cauda equina temporal horn, and the right insula, and diffuse involve- (Fig. 1D). ment along the cerebral and cerebellar leptomeninges Because of the leptomeningeal dissemination to the (Fig. 3C and D). The patient then developed respiratory brain and spine, chemotherapy with vincristine and carbo- distress and no further treatment was administered in platin was administered. However, the patient’s visual accordance with the wishes of her family members. She defect progressed to near-blindness after 3 weeks of died 1 week later after a total clinical course of less than 9 treatment. Another brain MRI revealed worsening of the months. leptomeningeal enhancement around the brain stem and multiple enhancing lesions at the rostrum of the left corpus callosum, third ventricle, both superior cerebellar pedun- 3. Discussion cles, and both cerebellar hemispheres. The weakness of the patient’s right arm also recurred, PCAs are benign and slow-growing, with a high rate of cure along with a feeling of numbness. Another MRI of the C-T after resection3; some 9% of these are found to be intra- spine revealed tumor seeding in the central canal with medullary.2 Tumor cell dissemination within the cerebro- related syringomyelia at C2eC6 and worsening of spinal ﬂuid (CSF) has primarily been reported for malignant

Figure 3 Brain MRI (axial T1-weighted MRI with gadolinium contrast) showing (A, B) leptomeningeal enhancement around the brain stem and cerebellar hemispheres and (C, D) multiple enlarged nodules in the cerebellum, the left medial temporal lobe, the right temporal horn, the right insular lobe, and diffuse involvement along the cerebral and cerebellar leptomeninges. 68 Y.-L. Chou et al.

Table 1 Spinal WHO grade I PCA with leptomeningeal dissemination. Study Age Sex Initial symptoms Primary Time to Recurrent symptoms Tumor spread (y) location recurrence Ng et al4 9 F Progressive C5eC7 2.5 y (brain) Occipital headaches, Sylvian ﬁssures, paraparesis vomiting, slurring of brainstem, speech, generalized cerebellar sulci toniceclonic convulsion Abel et al6 4 M Unsteadiness C7eT10 6 mo (spine) Decreasing bilateral Cisternal space and loss of 2.5 y (brain) leg function of midbrain, balance suprasellar space, auditory canal Our case 13 F Progressive right C3eC6 3 mo (spine) Right arm weakness, Cerebellum, left arm weakness 4 mo (brain) diplopia, blurred vision, medial temporal lobe, dizziness, headache, right temporal horn, poor appetite, limb right insular lobe, weakness cerebral and cerebellar leptomeninges, C2eC6, T11e12, L1e5

tumors, although it has also been observed in a few cases of chemotherapy regimen with carboplatin and vincristine,6 and PCA,4 and in most of these cases the tumor was intracra- both remained in a stable condition. However, radiotherapy nial.5 A review of the literature shows only two cases of and chemotherapy provided no benefits for our patient and intramedullary WHO grade I PCA associated with lep- the leptomeningeal dissemination progressed rapidly. tomeningeal dissemination (Table 1).4,6 The most common areas of leptomeningeal dissemination are the Sylvian fissures, basilar cisterns, and cauda 4. Conclusion equina, in which a slower rate of CSF flow and gravity may contribute to this phenomenon.6 In the present case, the We described a child with a spinal PCA that showed lep- tumor was disseminated, contrary to the pattern of CSF tomeningeal dissemination rostrally and caudally after flow, to the supratentorial areas. Furthermore, unlike other surgical resections. The clinical course for this case was cases in which only rostral dissemination had occurred,4,6 unique because of the rapid progression of PCA that our patient also presented with caudal dissemination. disseminated to the brain with neurogenic deficits, in spite Why a low-grade tumor acts in an aggressive manner of chemotherapy and radiotherapy. This case demonstrates remains uncertain. Earlier hypotheses speculated that that a low-grade astrocytoma may exhibit leptomeningeal surgical resection released tumor cells into the CSF, which dissemination with a rapid course and lead to death. Our resulted in seeding.7 However, there are numerous reports case demonstrates that a fatal outcome is a possibility in of dissemination at initial presentation. Studies have also certain cases of spinal PCAs in children after surgery. failed to demonstrate any correlation between dissemination and resection.3 Tihan et al described the pathological characteristics of References these tumors as a subset of low-grade gliomas or monomorphous pilomyxoid tumors.8 These have the same fea- 1. Mamelak AN, Prados MD, Obana WG, Cogen PH, Edwards MS. tures as a PCA, but have a more monomorphous and myxoid Treatment options and prognosis for multicentric juvenile pilocytic astrocytoma. J Neurosurg. 1994;81:24e30. character, no Rosenthal fibers or eosinophilic granular 2. Fernandez C, Figarella-Branger D, Girard N, et al. Pilocytic bodies, and have a more aggressive phenotype and poorer astrocytomas in children: prognostic factorsda retrospective outcome. However, in our case, the tumor had features study of 80 cases. Neurosurgery. 2003;53:544e553. more in keeping with a PCA than a pilomyxoid astrocytoma. 3. Buschmann U, Gers B, Hildebrandt G. Pilocytic astrocytomas The lesion had not undergone malignant transformation to with leptomeningeal dissemination: biological behavior, clin- a more aggressive histology. ical course, and therapeutical options. Childs Nerv Syst. 2003; Treatment for disseminated low-grade astrocytomas is 19:298e304. challenging. Radiotherapy is hardly ever used for children 4. Ng HK, Leung CH, Boet R, Poon WS. Spinal cord pilocytic as- because of the immature central nervous system.1 trocytoma with cranial meningeal metastases. J Clin Neurosci. e Chemotherapy with carboplatin, vincristine,9 cyclo- 2001;8:374 377. 5. Perilongo G, Garre` ML, Giangaspero F. Low-grade gliomas and hexylchloroethylnitrosourea (CCNU), 6-thioguanine (6-TG), 10 leptomeningeal dissemination: a poorly understood phenome- procarbazine, and temozolomide for low-grade astrocy- non. Childs Nerv Syst. 2003;19:197e203. tomas have led to good responses. In two previously reported 6. Abel TJ, Chowdhary A, Thapa M, et al. Spinal cord pilocytic cases of spinal PCA with leptomeningeal dissemination, one astrocytoma with leptomeningeal dissemination to the brain. patient accepted a course of cranial radiotherapy of Case report and review of the literature. J Neurosurg. 2006; approximately 30 Gy,4 whereas the other accepted a 105:508e514. Spinal cord PCA with brain & spine dissemination 69

7. Kocks W, Kalff R, Reinhardt V, Grote W, Hilke J. Spinal 9. Townsend N, Handler M, Fleitz J, Foreman N. Intramedullary metastasis of pilocytic astrocytoma of the chiasma opticum. spinal cord astrocytomas in children. Pediatr Blood Cancer. Childs Nerv Syst. 1989;5:118e120. 2004;43:629e632. 8. Tihan T, Fisher PG, Kepner JL, et al. Pediatric astrocy- 10. Aryan HE, Meltzer HS, Lu DC, Ozgur BM, Levy ML, Bruce DA. tomas with monomorphous pilomyxoid features and a less Management of pilocytic astrocytoma with diffuse lep- favorable outcome. J Neuropathol Exp Neurol. 1999;58: tomeningeal spread: two cases and review of the literature. 1061e1068. Childs Nerv Syst. 2005;21:477e481.