Diffuse leptomeningeal spread of supratentorial recurrent pilocytic astrocytoma in a child.

Dear Sir,

Pilocytic astrocytoma (PA) constitutes a significant proportion (25%) of pediatric primary brain tumors.[12] It primarily involves infratentorial compartment (vermis, cerebellar hemisphere), thalamus, hypothalamus, and optic pathway.[234] Supratentorial intraventricular location in young age (<3 years) is exceedingly rare.[2345] Natural history of PA is typically benign with favorable long-term outcome,[3] except rarely reported more aggressive clinical course.[1678910] Clinical factors predicting outcome in PA include age, location, and extent of resection.[13611] Histopathological and molecular parameters predicting outcome include p53 status, oligodendroglioma like features, calcification, vascular hyalinization, matrilin-2, and aldehyde dehydrogenase 1 family member L1 levels.[21112131415] Recent studies have pointed towards role of PI3K/AKT pathway activation in addition to mitogen-activated protein kinases/extracellular-signal-regulated kinase signaling pathway in biologically aggressive PA variants.[12] Differentiating classic PA from aggressive pilomyxoid astrocytoma variant (PMA) and anaplastic transformation is of paramount importance for prognostication and treatment algorithm.[1617] Three patterns of recurrence in PA are local recurrence, malignant transformation on long-term surveillance (usually > 10 years) and least commonly observed metastatic/multicentric disease on short-term surveillance.[18] We report an unusual case of recurrent supratentorial intraventricular PA presenting with a large local recurrence along with grossly disseminated disease along complete neuraxis in short span of 1 year following primary surgery.

Index case presented at 3 years age with delayed developmental milestones and increasing head size. Imaging [Figure 1] demonstrated supratentorial intraventricular lesion. Tumor decompression was done leaving small residual along posterior third ventricle [Figure 1]. Biopsy confirmed PA with 1% Milano Italia Borsa index. Owing to benign histopathological features and young age, decision to perform close follow-up was taken. He again presented within 1 year with rapidly increasing head size, recurrent vomiting and left-sided weakness. Imaging [Figure 2] showed local recurrence with metastatic deposits along entire neuraxis. Perfusion imaging [Figure 2] ruled out malignant transformation. Tumor debulking of recurrent lesion revealed recurrent PA [Figure 3]. Adjuvant chemo- and radiotherapy was given in view of widely metastatic disease. Retrospective evaluation of initial preoperative scans showed a small enhancing lesion in prepontine cistern, thereby suggesting rare synchronous, multifocal nature of PA at presentation.

Figure 1

Preoperative gadolinium magnetic resonance imaging contrast-enhanced magnetic resonance imaging brain axial, (a) coronal (b) and sagittal (c) sections demonstrating large, heterogeneously enhancing, predominantly solid, intraventricular lesion (thick arrow) in right lateral ventricle with posterior third ventricular extension and accompanying hydrocephalus. Small prepontine homogenously enhancing lesion (thin arrow) is suggestive of synchronous nature of disease. Postoperative contrast-enhanced magnetic resonance imaging brain axial, (d) coronal (e) and sagittal (f) sections demonstrating resolution of hydrocephalus, development of right subdural hygroma, residual primary lesion (thick arrow) in posterior third ventricular region with infratentorial growth and accompanying satellite nodules in posterior fossa and increasing synchronous primary lesion (thin arrow)

Figure 2

(a) Postoperative perfusion imaging confirmed no significant increase in relative cerebral blood volume (thick white arrow) in recurrent lesion. Follow-up contrast-enhanced magnetic resonance imaging brain axial, (b) coronal (c) and sagittal (d) sections demonstrating intensely enhancing, solid local recurrence in posterior third ventricle region (thick arrow), distant synchronous recurrence in prepontine cistern (thin arrow) along with multiple, nodular, metastatic deposits (thin arrow) along ependymal lining and diffuse uniform leptomeningeal enhancement in the entire neuraxis as highlighted in screening contrast-enhanced magnetic resonance imaging whole spine (e)

Figure 3

(a) Tumor with compact and microcystic areas, H and E, ×100; (b) mild to moderate nuclear pleomorphism with giant cells and hyalinized blood vessels, H and E, ×200; tumor cells were immunopositive for gial fibrillary acidic protein (c) while they were negative for p53, (d) isocitrate dehydrogenase-1. (e) There is no loss of ATRX immunoexpression. (f) The Milano Italia Borsa-1 labelling index is low (g)

Leptomeningeal disease (LD) is essentially a hallmark of malignant lesions.[19] Reported incidence of LD in low-grade glioma varies from 4% to 12%, 5% of them presenting at initial presentation.[2021] Factors predisposing for LD include tumor location adjacent to cerebrospinal fluid (CSF) space, antigenic profile, degree of adhesiveness, CD44 expression and metabolic pattern (protease secretion and growth factor pathway activation).[918222324] It usually presents with hydrocephalus, meningismus, focal neurological deficit, or seizure.[7] High-risk areas for LD include basilar cistern, sylvian fissure, and cauda equina, being gravity dependent areas and having sluggish CSF flow.[19] Amplification of epidermal growth factor receptor gene located at short arm of chromosome 7 has been recently attributed to pathophysiology for LD, making it a potential target for alteration of natural history in high-risk cases.[25] PA usually presents with a stereotypic radiographic pattern of cyst with a mural nodule, predominantly solid lesion with minimal cystic component is seen in <17% of cases.[13] Clinical-pathologic dissociation is an area of ongoing debate in selective subgroup of PA patients having atypical natural history despite benign histological features. Histological differentiation from more aggressive PMA phenotype (common in infants and young children) can be done based on more monomorphous and myxoid character, absence of Rosenthal fibers and eosinophilic granular bodies in PMA.[17] Another close differential is anaplastic PA, characterized by hypercellularity, moderate to severe cellular atypia, brisk mitotic activity (>4/high-power field) with or without necrosis.[1626]

Screening of entire neuraxis is warranted in intraventricular lesions despite benign natural history. Since CSF evaluation yields inconsistent results in LD, gadolinium magnetic resonance imaging is considered gold standard for its diagnosis.[27] Treatment of LD in PA is typically adjuvant in form of multi-agent chemotherapy, radiotherapy or stereotactic radiosurgery.[282930] To conclude, solid supratentorial intraventricular PA presenting as recurrent disseminated LD in less than a year is unusual and highlights importance of early surveillance in large lesions having intraventricular locations for timely adjuvant therapy and optimal outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.