PATH-48. Molecularly defined glioblastoma with combined gain of chromosome 7 and loss of chromosome 10 presenting microscopically as a low-grade, benign, multi nodular vacuolating tumor

Abstract We report a case of a 38-year-old German male, without co-morbidities or previous hospitalization, who presented with new onset seizures. Cranial MRI revealed three ill-defined lesions with no contrast enhancement on the left frontal lobe, left high fronto-parietal lobe, and left thalamus. All lesions had T1-hypointense, T2/FLAIR hyperintense signals, without evident restricted diffusion. MR spectroscopy showed elevated choline relative to the creatine and N-acetyl aspartate metabolites, and absence of lactate and lipid peaks—all suggestive of a low-grade glioma. He underwent image-guided left frontal craniotomy, excision of tumor without any intra- or post-operative complications, and was discharged without any neurologic deficits or seizure recurrence. Astonishingly, histopathologic findings showed a neoplasm composed of discrete nodules with monomorphic neuronal elements, which were weakly positive to synaptophysin, on a delicate fibrillar matrix with conspicuous vacuolar change—indicative of a Multinodular and Vacuolating Neuronal Tumor (MVNT), a rare benign neuronal tumor listed only as an architectural pattern in the World Health Organization (WHO) Classification of CNS tumors in 2016 but was elevated to a Grade 1 tumor in the most recent 2021 Classification. Moreover, the tumor was had Ki-67% index of <1%, no necrosis, mitoses or microvascular proliferation and were GFAP, p53 and IDH1 negative on immunohistochemical staining. Because of the rarity of the case, the specimen was also sent for next generation sequencing assay which detected a combined chromosome 7 gain and chromosome 10 loss, and PTEN p.G165R mutation. These molecular features support the diagnosis of a molecularly defined Glioblastoma, IDH-wildtype, CNS WHO Grade 4 tumor, regardless of histologic grade and MVNT features earlier defined. This case may support the need for further molecular studies for similarly presenting benign, low grade CNS tumors.