Granular cell astrocytoma - a diagnostic conundrum

Granular cell astrocytoma (GCA) is an aggressive variant of astrocytoma characterised by predominantly round-to-polygonal cells with abundant eosinophilic granular cytoplasm. This tumor usually lack the morphological signatures of conventional astrocytoma and are devoid of typical features which define a malignant neoplasm, leading to potential misdiagnosis. We report GCA in a 50-year-old man presenting with severe headache along with vertiginous sensation and sensory seizures of left upper limb for past two months. Imaging showed multiple intra-axial, hyperintense space-occupying-lesions in bilateral anterior temporal lobe, left parietal lobe, left thalamus and cerebellum, raising possibility of lymphoma/metastases. Histopathological examination revealed sheets of large polygonal cells with distinct cellular outline, ample amount of eosinophilic PAS-positive granular cytoplasm, eccentrically placed irregular, round-to-ovoid nuclei with occasional prominent nucleoli. On immunohistochemistry, tumour cells were diffusely immunopositive for Olig2, S100, EMA, lysozyme and CD68 while they were immunonegative for GFAP, LCA, pan-CK, TTF-1, TFE-3, PAX-8, SOX10, MAP2, MBP, NF, H3K27M, H3K27me3, p53, IDH1(R132H), CD1a, langerin and BRAFV600E. Numerous scattered macrophages were highlighted by CD163. MIB 1-labelling-index was approximately 5-6%. Overall features were congruous with final diagnosis of GCA. GCAs exhibit genetic alterations similar to glioblastoma and are seen to behave in a belligerent manner irrespective of their morphological grade. Thereby, they warrant early diagnosis for conducive patient management.

Keywords: Granular cell astrocytoma; IDH wild type glioma; aggressive gliomas; brain tumor; glial tumors.