Synchronous multicentric glioblastoma with PNET and O subtypes: Possible pathogenesis
A 47-year-old Caucasian male with no past medical history, presented with a four week history of episodic frontal headache and easy fatiguability. He also noted to have progressive difficulty with recall which was associated with occasional dizziness and an unsteady gait. On examination, there were no cranial nerve abnormalities and other focal neurologic findings. The rest of his clinical examination was unremarkable.\nMagnetic resonance imaging (MRI) brain scan was performed which revealed two intra-axial lesions with similar imaging characteristics []. The first lesion approximated 70 × 48 mm and was located at the left temporal lobe while the second lesion was at the left frontal parasagittal region and approximated 34 × 31 mm. Both lesions had solid and necrotic-cystic areas with areas of T1 hypointensity, T2 hyperintensity, with heteorgenous enhancement post-gadolinium contrast. Susceptibility within the masses suggested intra-lesional haemorrhage and/or calcification. Both lesions were associated with significant perilesional oedema causing mass effect and midline shift to the right. The radiological diagnosis was multi-centric glioblastomamultiforme, with differential diagnosis of metastasis.\nAdditional imaging workup included computed topography scans of his thorax, abdomen and pelvis and MRI of his whole spine, which did not demonstrate any further lesions.\nThe patient underwent an awake craniotomy for gross total resection of the left frontal and parieto-temporal tumours. Intraoperative frozen section was reported as suggestive of a high grade glioma. The patient recovered well postoperatively with no new focal neurological deficits. Post-operative MRI brain scan was performed 48 hours after surgery and showed no gross evidence of residual tumor. He was subsequently referred to the medical and radiation oncology teams for adjuvant therapy, and has since commenced on both chemotherapy (temozolamide) and radiotherapy to both cranium and spine.\nThe resection specimen from the left temporal lobe tumour showed two histologically distinct components. In some areas, the tumour resembled a glioblastoma (WHO grade IV) []. These areas consisted of a cellular proliferation of astrocytes with markedly enlarged, irregular, pleomorphic nuclei and moderate to abundant quantities of fibrillary cytoplasm. Neoplastic gemistocytic astrocytes and multinucleated astrocytes were seen. There was brisk mitotic activity, microvascular proliferation and pseudopalisading necrosis. In other areas, the tumour resembled a central nervous system primitive neuroectodermal tumour (CNS PNET, WHO grade IV) []. These latter areas consisted of densely packed cells with hyperchromatic oval to elongated nuclei, high nuclear cytoplasmic ratios, brisk mitotic activity and karyorrhexis. There were also areas where cells from both tumour types were closely intermingled. The lesion included large confluent areas of coagulative tumour necrosis. Immunoperoxidase staining for glial fibrillary acid protein (GFAP) was positive in the glioblastoma component [] and negative in the CNS PNET areas, while synaptophysin was positive in the CNS PNET areas [] and negative in the glioblastoma cells. The features were compatible with a malignant glioma with a PNET-like component.[]\nThe resection specimen from the left frontal lobe tumour showed features of a glioblastoma with an oligodendroglial component (WHO grade IV). The glioblastoma consisted of a cellular proliferation of astrocytes with irregular, hyperchromatic, pleomorphic nuclei and fibrillary cytoplasm. There was brisk mitotic activity, microvascular proliferation and pseudopalisading necrosis []. Focally, there was a proliferation of cells resembling oligodendrocytes with round regular nuclei, clear cytoplasm and distinct cytoplasmic borders. The oligodendroglial population was associated with a branching capillary network [].