Rare glioblastoma subtype masquerading as a poorly differentiated carcinoma: illustrative case.

Background: Glioblastoma (GBM) with a primitive neuronal component (PNC) is a recently characterized subtype with a characteristic (epi-)genetic profile and ambiguous microscopic features mimicking a metastasis, making intraoperative diagnosis challenging.

Observations: A 62-year-old female presented with word-finding difficulties. MRI showed 2 contrast-enhancing lesions in the temporal lobe. Intraoperatively, a subcortical, well-circumscribed lesion without thrombosed vessels was observed, which is considered unusual for a glial tumor. Minimal microscopic fluorescence was noted after 5-aminolevulinic acid administration. Intraoperative pathological analysis favored a poorly differentiated carcinoma or lymphoma, with a malignant glioma less likely. Immunohistochemical stains were inconclusive; however, tissue submitted for nanopore sequencing suggested a rare subtype of GBM. Subsequent analysis on the Infinium BeadChip methylation microarray confirmed the diagnosis of GBM with a PNC, WHO grade 4.

Lessons: GBM with a PNC is subject to misdiagnosis due to radiographical and pathological features mimicking metastasis. Definitive diagnosis is facilitated with DNA methylation profiling. This case illustrates the limitations and potential pitfalls of conventional intraoperative diagnosis for CNS tumors that now explicitly require molecular testing. Nanopore sequencing, a rapid methylation profiling method, is emerging as a cost-effective and accurate adjunct to traditional frozen section diagnosis. https://thejns.org/doi/10.3171/CASE24553.