Radiology-Pathology and Surgical Correlation in Astroblastoma

DISCUSSION

Astroblastoma is a rare circumscribed astrocytic glial neoplasm, representing <3% of all gliomas, affecting mainly the cerebral hemispheres with a peak incidence between 10 and 30 years of age. Some series describe a higher prevalence in female patients.^3,5,6 Its biologic behavior ranges from indolent to aggressive lesions, and a World Health Organization grade has not yet been attributed.¹

Historically, astroblastomas were initially described by Bailey and Cushing in 1924,⁷ but their histopathologic and molecular features overlapping with diffuse astrocytomas, pleomorphic xanthoastrocytomas, and ependymomas have led to decades of confusion. It has been described as a stage of glioma dedifferentiation, a fiber-producing astrocytoma, or rare tanycytes or ependymal astrocyte neoplasm. The term itself is confusing because they are not notoriously astrocytic nor blastic. Only recently, assisted by molecular advances, their reliable diagnostic criteria have been established.^3,5,6 Recent genetic profiling of high-grade neuroepithelial tumors revealed that many of the lesions with recurrent MN1 mutations had histologic features of astroblastoma.⁸

The MN1 gene, located in chromosome 22, is involved in meningioma and myeloid leukemia pathogenesis, and its rearrangements can be detected through DNA methylation. In addition to astroblastoma, many central nervous system primary tumors may express MN1 alterations, like circumscribed and diffuse gliomas. Recently, this molecular signature has been attributed to the latter for more accurate diagnosis, but further research is needed to establish the ways these rearrangements act in astroblastoma and how it differs from manifestations in similar neuroepithelial tumors.^9,-,12

Therefore, astroblastoma still shows molecular heterogeneity, with no exclusivity of MN1 mutations in all cases, with most being classifiable within the MN1 or BRAF DNA methylation groups.⁹ Despite minor heterogeneity, MN1 alterations have become the defining feature of this condition in the 2021 World Health Organization CNS tumor classification, which is now called MN1-altered astroblastoma.¹⁰

Imaging usually reveals a supratentorial peripherally located solid-cystic mass with little or no vasogenic edema and rarely adjacent parenchyma infiltration (Figure 4). A bubbly aspect is frequently seen due to multiple cysts. Calcifications are seen in most cases, more commonly in a punctate pattern within the solid part. The solid component is usually isointense on T1 and T2/FLAIR, with a heterogeneous gadolinium enhancement and intermediate ADC values ranging from 1190 to 1250 × 10⁻⁶ mm²/s. Cystic areas are hyperintense on fluid-sensitive sequences and show facilitated diffusion. No MR imaging features can help differentiate indolent and malignant astroblastomas. Atypical presentations include solid masses with central necrosis and an irregularly rimmed cyst.^3,6,13,14

Imaging differential diagnosis includes supratentorial ependymomas, astrocytomas, and AT/RT.

YAP1 fusion-type ependymoma also presents as a heterogeneous mass with cystic areas. However, it is more prevalent among younger children, usually younger than 3 years of age. Due to its fibrillary components and infiltrative nature, perilesional edema and microinvasion are significantly more evident in ependymomas than in astroblastomas.^6,15

High-grade astrocytomas manifest less frequently in children but also have imaging features that overlap with astroblastoma because presentation may also demonstrate a heterogeneous supratentorial mass. Similar to ependymomas, mass effect and perilesional infiltration are more striking in astrocytomas compared with astroblastomas.¹⁶

AT/RT may also present as large supratentorial heterogeneous masses, with a peak incidence in younger children around 3 years of age. Imaging demonstrates solid-cystic masses, with frequent hemorrhage and intensely restricted diffusion, in contrast to astroblastoma. Leptomeningeal dissemination is also frequent in AT/RT but not expected in astroblastoma.⁴

Macroscopically, astroblastomas present as well-circumscribed solid-cystic masses with a bubbly appearance secondary to cystic degeneration. Microscopic features include elongated eosinophilic cells with GFAP-positive processes oriented radially from the cell body toward a usually hyalinized vessel, resembling ependymal perivascular pseudorosettes, but with a tapering or columnar aspect. Immunohistochemistry shows positivity for epithelial membrane agent and D2-40. GFAP, OLIG2, and S-100 are often positive to variable extents (Fig 5).³

Histologic features that indicate an aggressive biologic behavior include increased mitotic activity, palisading necrosis, high cellularity, vascular proliferation, and a high Ki-67 index. Higher Ki-67 indexes are also related to prognosis and survival rates, with a cutoff of 4%.¹

A primary histopathologic differential diagnosis includes high-grade astrocytomas, supratentorial ependymomas, atypical teratoid/rhabdoid tumors, and gemistocytic astrocytoma and these are better discussed in the previous session (See Pathology: Astroblastoma).

Treatment relies on gross surgical resection whenever possible. Low-grade lesions with satisfactory excision are usually followed up. Patients with incomplete resection or high-grade features in histology usually undergo adjuvant radiation and systemic chemotherapy with temozolomide.^12,17

Our patient had an excellent postoperative evolution, and 6-month control imaging shows no signs of recurrence. However, the multidisciplinary team opted for isolated adjuvant surgical cavity radiation due to faint 5-ALA surgical cavity positivity, necrosis, and mitotic activity. Systemic chemotherapy was not initiated.

Due to its rarity and imprecise imaging and histopathologic features, misdiagnosis is frequent. The ensemble of nonspecific features is the key. Astroblastoma should be remembered when this set of features is present, especially in a young female patient with a large, well-circumscribed hemispheric solid-cystic lesion.