Pilocytic astrocytoma (World Health Organization grade I) has a benign biologic behavior, and one of the highest survival rates of any type of astrocytoma. However, it occasionally exhibits an atypical behavior characterized by local recurrence, or, in rare cases, malignant transformation and metastasis.Reference Mamelak, Prados, Obana, Cogen and Edwards 1 – Reference Civitello, Packer, Rorke, Siegel, Sutton and Schut 3 Leptomeningeal dissemination of a pilocytic astrocytoma in children, especially young children, is very rare.Reference Mamelak, Prados, Obana, Cogen and Edwards 1 – Reference Civitello, Packer, Rorke, Siegel, Sutton and Schut 3 We describe a case of a pilocytic astrocytoma with leptomeningeal dissemination in a young boy.
A 2-year, 9-month-old boy was admitted in 2007 with a 6-month history of progressive left-sided weakness. Examination revealed left-side hemiparesis with partial pseudobulbar palsy, increase tendon reflexes in his left limbs, and a positive Babinski sign on the left. Cranial magnetic resonance imaging (MRI) scans disclosed a solid, well-circumscribed, contrast-enhancing mass in the right thalamus and basal ganglia, with a cystic component (Figure 1). Gadolinium-enhanced T1-weighted axial (Figure 1A) and coronal (Figure 1B) images revealed a nonenhancing cystic mass with an intensely enhancing mural nodule (7.9×5.4×6.4 cm) over the right basal ganglion and thalamus. A subtotal resection was chosen over gross total resection because the location of the tumor in the thalamus is an eloquent area. A repeat MRI was performed immediately after surgery to serve as the basis for future comparison.
Figure 1 (A) Gadolinium-enhanced axial T1-weighted (A) axial and (B) coronal MRI scans of a nonenhancing cystic mass with enhancing mural nodule over the right basal ganglion and thalamus. (C) MRI taken 16 days after surgery showed diffuse enhancement (arrows) and tumor tissue along the surgical tract, with extension into the subdural space, and residual tumor in the thalamic area (arrow head). (D) Axial and (E) coronal T1-weighted MRI of the brain immediately before chemotherapy. (F) MRI performed 4 months after completion of chemotherapy revealed calcification, and no residual disease or additional lesions.
The patient’s postoperative course was unremarkable, and he could walk without assistance. Gadolinium-enhanced coronal T1-weighted MRI 16 days after surgery (Figure 1C) showed diffuse enhancement not seen in the MRI scans obtained immediately postoperatively, indicating possible tumor seeding along the surgical tract with extension into the subdural space. Residual tumor in the thalamic area was also noted. Reoperation was not considered because the areas of seeding were inoperable. No seeding of the spinal leptomeninges was noted in the spine MRI scan. Repeat MRI performed 10 weeks postoperatively and immediately before the start of chemotherapy showed similar results (Figure 1D, E).
Histopathological examination of the surgical specimen showed a moderately cellular glial tumor with spindle-shaped cells arranged in bundles. A biphasic pattern of loose glial tissue and compact piloid tissue was noted (Figure 2A). The piloid tissue component was composed of fusiform cells with wavy fibrillary processes and Rosenthal fibers, and the tumor was positive for glial fibrillary acid protein and vimentin, indicating astrocytic origin (Figure 2B, C). The Ki-67 index was 2% to 3% (Figure 2D). Based on the histopathological examination, the final diagnosis was pilocytic astrocytoma.Reference Aichholzer, Mazal and Haberler 4
Figure 2 (A) Histological examination showed a biphasic pattern of loose glial tissue and compact piloid tissue. (B) The piloid tissue component was composed of fusiform cells with wavy fibrillary processes and Rosenthal fibers. (C) Tumor cells were diffusely positive for glial fibrillary acidic protein (immunostain, 100×). (D) Ki-67 index was 2% to 3%.
The patient received a six-course regimen of vincristine (1.5 mg/m2) and carboplatin (175 mg/m2). MRI performed 4 months after completion of chemotherapy revealed only calcification in the medial margin, but no residual or additional lesions (Figure 1F). No recurrence was noted in the subsequent 6 years of follow-up.
Leptomeningeal dissemination of pilocytic astrocytoma is uncommon, and as there have been only a few cases reported, its incidence is undetermined. In a review of the literature, we identified 29 cases of tumor recurrence/metastasis attributed to tumor seeding along the surgical, biopsy, or the aspiration tract, and five were malignant anaplastic astrocytomas or glioblastoma multiforme, unlike the relatively benign astrocytoma in our case. In more than half of cases (52%), recurrence or metastasis was not detected until more than 1 year after the invasive intervention, with the longest interval being 21 years. It is estimated that 5% of all pediatric low-grade gliomas have leptomeningeal dissemination at diagnosis, and 7% to 10% have dissemination at the time of progression.Reference Perilongo, Garrè and Giangaspero 5 Studies have reported an incidence of dissemination ranging from 4% to 12%.Reference Mamelak, Prados, Obana, Cogen and Edwards 1 , Reference Civitello, Packer, Rorke, Siegel, Sutton and Schut 3
Specific extracellular substrates such as proteins, glycosaminoglycans, parenchymal cells, adhesion molecule production, protease secretion, growth factor pathway activation, immunogenicity of the tumor cells, and mechanical factors can all aid the leptomeningeal spread of pilocytic astrocytomas.Reference Pollack, Hurtt, Pang and Albright 2 , Reference Civitello, Packer, Rorke, Siegel, Sutton and Schut 3 Surgical manipulation can also promote dissemination.Reference Mamelak, Prados, Obana, Cogen and Edwards 1 Patients with dissemination from a pilocytic astrocytoma may remain asymptomatic and survive for a long period.Reference Mamelak, Prados, Obana, Cogen and Edwards 1 , Reference Pollack, Hurtt, Pang and Albright 2
Complete resection can be curative in pediatric patients with low-grade gliomas, with a survival rate of more than 90% at 10 years.Reference Gnekow, Falkenstein and von Hornstein 6 If only partial excision can be performed, chemotherapy may be recommended, especially if the patient is younger than 3 years of age.Reference McLaughlin 7 Radiation therapy is not typically used in younger patients because it can produce long-term neurocognitive and endocrine toxicity. Genkow et alReference Gnekow, Falkenstein and von Hornstein 6 reported that dissemination, age <1year, and nonpilocytic histology were unfavorable factors for progression following radiotherapy, and diencephalic syndrome, dissemination, and age ≥11years were unfavorable factors following chemotherapy. Ater et alReference Ater, Zhou and Holmes 8 found that factors independently predictive of worse survival were younger age, tumor size >3 cm2, and tumor location in the thalamus. In summary, the case reported provides neuroimaging and pathological findings of a pilocytic astrocytoma in a 2-year-old child with dissemination characteristics more commonly seen in World Health Organization grade III or IV astrocytomas. Neurosurgeons operating on patients with these tumor types should be aware of the possibility of tumor seeding along the operative tract. Even for a low-grade astrocytoma, as in our case, imaging at regular intervals after surgery to screen for tumor seeding along the surgical tract can be critical to the final outcome.
DISCLOSURES
The authors do not have anything to disclose.
