Pilocytic Astrocytoma with Adipocytic Differentiation: A Rare Histological Variation.

Lipidization of the low-grade astrocytic tumor is a very rare phenomenon. We report a case of pilocytic astrocytoma with adipocytic differentiation involving the left cerebellar hemisphere and pontis in an 11-year-old boy. Till date, very few such cases have been reported in children. A young boy presented with a clinical picture suggestive of cerebellar dysfunction since 7 months. Imaging revealed a mass lesion involving the left cerebellar hemisphere measuring 4.5×4.1cm. Subtotal excision of the tumor was carried out. Microscopic features were typical of pilocytic astrocytoma but with extensive lipidization of tumor cells. Immunohistochemically, the tumor cells were immunoreactive to glial fibrillary acidic protein, S-100, and immunonegative to p53 and isocitrate dehydrogenase 1. Ki-67 labeling index was 1%. The patient had an uneventful postoperative period and is doing well on follow-up. An extensive review of prior work was carried out to elucidate the clinicopathologic significance of this entity, if any, with special reference to the pediatric age group.

INTRODUCTION

Primary glial tumors rarely show mesenchymal differentiation. Lipomatous change in astrocytic tumors is even rarer, and it was first described by Kepes and Rubinstein[1] in 1981. Astrocytic tumors showing lipomatous differentiation include the ependymoma and pilocytic astrocytoma.[2] Recent work on the ependymoma has suggested that lipomatous differentiation may be a harbinger of a “tenacious” biological course.[3] The clinical, radiological, and histopathological features of cases showing this pattern have seldom been studied. Herein, one such case of adipocyte-like morphology in a pilocytic astrocytoma is reported. Only few cases have been reported in the pediatric age group, with the current case being the first from India. A brief literature review is also incorporated to elucidate the clinicopathologic connotations of this phenomenon, especially in children.

CASE REPORT

An 11-year-old male child was referred to the Neurosurgery Outpatient Department of our institute with complaints of headache, fatigue, intermittent vomiting, imbalance, and swaying in either direction while walking since 7 months. There was no history of fever, seizures, or trauma. Laboratory investigations revealed all biochemical and hematological parameters to be within normal limits. Clinical examination revealed a broad-based ataxic gait, ocular nystagmus, and past pointing on the finger–nose test. Neck rigidity and sensory deficits were absent.

Non-contrast sequential axial computerized tomography (CT) scans showed an iso–hypodense left cerebellar lesion measuring 5.4 × 5 cm with dilated lateral and third ventricles pointing to an obstructive hydrocephalus. Perilesional white matter hypodensity suggesting edema with mass effect was seen. Magnetic resonance imaging showed a well-lobulated intense peripherally enhancing posterior fossa mass lesion involving the left cerebellar hemisphere and left brachium pontis causing midline shift. The lesion was hyperintense on T2-weighted/fluid-attenuated inversion recovery (FLAIR) images and isointense to hypointense on T1-weighted scans [Figure 1]. Abdominal and chest CT as part of staging workup did not reveal any metastases. The patient had a prior operative intervention 2 months back at a local center, where a right ventriculoperitoneal shunt had been inserted.

Figure 1

(A) Contrast enhanced computerized tomography image showing a left cerebellar hemisphere lesion with peripheral enhancement and perilesional edema. (B) Thin-walled left cerebellar space occupying lesion hypodense on T1-weighted and (C) hyperdense on T2-weighted images. (D) FLAIR image showing no suppression

OPERATIVE FINDINGS

Subtotal tumor excision was performed via a midline suboccipital craniotomy. Peroperatively, a solid cystic posterior fossa mass was noted 2 cm below the surface. After decompressing the cystic component, a grey–white moderately vascular mural nodule was observed. As the lesion had an ill-defined plane of cleavage, a small portion infiltrating the roof of the fourth ventricle could not be completely excised.

HISTOPATHOLOGICAL FINDINGS

Histologically, a cellular tumor was noted, which was composed of bipolar astrocytes in sheets and fascicles. Hypercellular and hypocellular areas were noted with individual tumor cells having a piloid configuration. Microcystic foci and hyalinized vessels were interspersed. Large areas (60%–70%) of the tumor showed an adipocytic appearance on hematoxylin and eosin stain (H&E) [Figure 2A and B]. Periodic acid–Schiff and Alcian blue stains were carried out to rule out the presence of mucinous change, which in this case was negative. Cytoplasmic rims of the tumor cells were immunopositive for glial fibrillary acidic protein (GFAP) and S-100, ascribing to a glial lineage of the tumor [Figure 2C and D]. The tumor cells were negative for isocitrate dehydrogenase 1 and p53. Ki-67 labeling index was 1%. Extensive sampling failed to reveal histologically aggressive features of necrosis, atypia, mitotic figures, or vascular proliferation. A clear transition between the non-lipomatous and lipidized areas was not apparent in this case, with the fat vacuoles blending in with individual cells. A diagnosis of pilocytic astrocytoma (the World Health Organization Grade I) with lipomatous change was offered. The patient is currently on close follow-up and is doing well.

Figure 2

(A) Photomicrographs showing sheets of astrocytic tumor cells in a coarse fibrillary background (H&E; 400×). (B) High-power view shows tumor cells with eccentrically placed nuclei and prominent cytoplasmic vacuolation (H&E; 600×). (C and D) The tumor cells show cytoplasmic positivity with GFAP and S-100 (GFAP, S-100; 400×)

DISCUSSION

Lipidization of glial tumors is a well-recognized, albeit, infrequently encountered phenomenon. The exact etiopathogenesis of glial lipidization is not well understood. Some of the proposed mechanisms behind this change include anoxic damage, hamartomatous change, adipocytic metaplasia of neuroectodermal cells, and fatty degeneration of neoplastic cells.[4] Immunoexpression of the same tumor cells to both GFAP and S-100 may point toward true adipocytic metaplasia in glial cells as seen in our case, though many authors negate this hypothesis.[5]

Lipomatous differentiation in tumors of central nervous system (CNS) may be seen in two forms. The first is the xanthomatous change, which refers to the presence of multiple intracytoplasmic lipid vacuoles, as seen in lipidized glioblastoma and pleomorphic xanthoastrocytoma.[6] The other form is characterized by an adipocyte-like morphology of an individual tumor cell, that is, the presence of a single coalescent lipid vacuole within the cytoplasm. This has been described in CNS neurocytoma, ependymoma, cerebellar neurolipocytoma, and medulloblastoma.[7] Lipomatous differentiation in pilocytic astrocytoma is one of the rarely reported entities.

A review of the literature identified four prior cases of astrocytoma showing lipomatous differentiation in children, clinicopathologic profile of which is summarized in Table 1. The mean age of involvement was 8.8 years. Four cases have previously been described in the pediatric age group. The majority of these cases (60%) showed definite piloid-like features histologically. Another case that was devoid of piloid features initially, developed frank pilocytic astrocytoma on follow-up. Most cases were well circumscribed, and the tumor was totally excised in three of them. A subtotal tumor excision was performed in our case because of lack of a definite cleavage plane.

Table 1

Review of cases of astrocytoma with lipomatous change reported in the pediatric age group

Notably, three of the four previously reported pediatric cases showed local recurrence, secondary malignancy, or fatality. Our case, however, at 1 year of follow-up has not shown any recurrence or metastases. The management protocol employed herein involved gross resection followed by radiological surveillance. The role of adjuvant therapy is still not known. Other tumors with lipidization such as liponeurocytoma and lipidized medulloblastoma show favorable prognosis as compared to their corresponding non-lipidized variants.[6] However, a recent report on the “lipomatous” ependymoma suggested a tendency to recur.[3]

To conclude, lipidization is a rare change in pilocytic astrocytoma and merits a cautious follow-up of the patient. Larger retrospective studies are required to validate the exact clinical outcome of these cases.

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Conflicts of interest

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