Coexisting cancer stem cells with heterogeneous gene amplifications, transcriptional profiles, and malignancy are isolated from single glioblastomas.

Glioblastoma (GBM) is known as an intractable, highly heterogeneous tumor encompassing multiple subclones, each supported by a distinct glioblastoma stem cell (GSC). The contribution of GSC genetic and transcriptional heterogeneity to tumor subclonal properties is debated. In this study, we describe the systematic derivation, propagation, and characterization of multiple distinct GSCs from single, treatment-naive GBMs (GSC families). The tumorigenic potential of each GSC better correlates with its transcriptional profile than its genetic make-up, with classical GSCs being inherently more aggressive and mesenchymal more dependent on exogenous growth factors across multiple GBMs. These GSCs can segregate and recapitulate different histopathological aspects of the same GBM, as shown in a paradigmatic tumor with two histopathologically distinct components, including a conventional GBM and a more aggressive primitive neuronal component. This study provides a resource for investigating how GSCs with distinct genetic and/or phenotypic features contribute to individual GBM heterogeneity and malignant escalation.

Glioblastoma/high-grade glioma with a primitive neuronal component including rhabdoid differentiation that was difficult to diagnose: A case report.

Glioblastoma with a primitive neuronal component (GBM-PNC) is a rare subtype. In this case, GBM-PNC was difficult to diagnose conclusively because the specimen consisted of only a few high-grade glioma components. A 73-year-old woman presented with sensory aphasia and minor right-sided hemiplegia. Imaging revealed a neoplastic lesion with a maximum diameter of approximately 5 cm in the left frontal lobe for which surgery was performed. Histologically, most atypical cells were immature components with high nuclear-cytoplasmic ratios and immunopositive for neuroendocrine markers. Minor components of atypical glial cells were found at tumor margins. Rhabdoid cells were observed in undifferentiated components. Immunostaining was positive for glial fibrillary acidic protein (GFAP), nestin, and Olig2 in both undifferentiated and atypical glial cells. The major undifferentiated components showed significantly low GFAP, nestin, and Olig2 expression levels within the foci of the undifferentiated components, in contrast to the atypical glial component, neurofilaments and synaptophysin were immunopositive for undifferentiated components. Rhabdoid cells were immunopositive for myogenin, desmin, and HHF35, suggesting their differentiation into striated muscles. This was a particularly rare case because rhabdoid differentiation was observed in PNC.

Glioblastoma with a primitive neuroectodermal component: two cases with implications for glioblastoma cell-of-origin.

BACKGROUND: Glioblastoma (GBM) is the most common primary brain malignancy, but much remains unknown about the histogenesis of these tumors. In the great majority of cases, GBM is a purely glial tumor but in rare cases the classic-appearing high-grade glioma component is admixed with regions of small round blue cells with neuronal immunophenotype, and these tumors have been defined in the WHO 2016 Classification as "glioblastoma with a primitive neuronal component." METHODS: In this paper, we present two cases of GBM-PNC with highly divergent clinical courses, and review current theories for the GBM cell-of-origin. RESULTS AND CONCLUSIONS: GBM-PNC likely arises from a cell type competent to give rise to glial or neuronal lineages. The thesis that GBM recapitulates to some extent normal neurodevelopmental cellular pathways is supported by molecular and clinical features of our two cases of GBM-PNC, but more work is needed to determine which cellular precursor gives rise to specific cases of GBM. GBM-PNC may have a dramatically altered clinical course compared to standard GBM and may benefit from specific lines of treatment.