Synchronous multicentric glioblastoma with PNET and O subtypes: Possible pathogenesis

Abstract

Background: Glioblastomas (GBM) are highly infiltrative, cellular and mitotically active tumors with large histologic variations within and between tumours. Several subtypes have been described including the GBM with oligodendroglial differentiation (GBM-O) and primitive neuroectodermal tumour components (GBM-PNET). We report the first described case of a patient with synchronous multi-centric GBM-O and GBM-PNET components.

Case description: A patient, who presented with a short history of progressive headache and difficulty with memory recall, was found on MRI imaging to have two intracranial lesions. These showed heterogeneous enhancement and were found in the left frontal and left temporal regions. The patient underwent gross total resection of these two lesions which were found to show GBM-O and GBM-PNET differentiations.

Conclusion: Although tumour cell migration in the context of GBM is a well-recognized phenomenon, the traditional hypothesis is not able to satisfactorily explain this case of multicentric GBM whereby the two lesions demonstrate different cell origins. More current understanding of the migratory pathways from the subventricular zone provide an alternate and plausible pathway that fits our patient's unusual diagnosis.

Keywords: Glioblastoma; migration; oligodendroglial differentiation; pathogenesis; primitive neuroectodermal tumour; subventricular zone.

Figure 1

T2-weighted (a) and T1-weighted (b) MRI showing synchronous tumour in the left frontal and temporal regions with solid and necrotic-cystic areas with significant perilesionaledema. (c) T1-weighted image post-gadolinium contrast showed heterogenous enhancement

Figure 2

(a) The glioblastoma component of the left temporal lobe tumour showing neoplastic astrocytes with pleomorphic nuclei and fibrillary cytoplasm. There was frequent mitotic activity and microvascular proliferation (right of field) (H and E, ×200). (b) The CNS PNET component of the left temporal lobe tumour showing densely packed cells with hyperchromatic oval to elongated nuclei, high nuclear cytoplasmic ratios and brisk mitotic activity (H and E, ×400). (c) GFAP staining in the glioblastoma cells (GFAP, ×200). (d) Synaptophysin was positive in the PNET-like component (Synaptophysin ×400)

Figure 3

(a) The glioblastoma component of the left frontal lobe tumour showing neoplastic astrocytes with pleomorphic nuclei and fibrillary cytoplasm. There was frequent mitotic activity, microvascular proliferation (right of field) and pseudopalisading necrosis (left of field) (H and E, ×200). (b) The oligodendroglial component of the left frontal lobe tumour (H and E, ×400)

Figure 4

The likely migratory pathway of transformed GSCs and, or their progenitors from the stem-cell enriched subventricular zone (SVZ) to the subcortical region