Supratentorial Primitive Neuroectodermal Tumors of the Central Nervous System in Adults

Abstract

Advances in understanding the molecular basis of primitive neuroectodermal tumors of the central nervous system (CNS-PNET) biology are critical to improve patient outcome. Recently, new data on their molecular features have been reported, suggesting that supratentorial PNET (s-PNET) in adult patients may represent a specific tumor entity among CNS-PNETs. In this study, we analyzed the clinicopathologic and molecular features of 12 cases of s-PNET in adult patients. The follow-up analysis showed that these tumors have an aggressive clinical behavior. At the histopathologic level, they resembled their pediatric counterpart, showing a variable spectrum of neuronal differentiation. These cases did not show astrocytic differentiation; therefore, they did not qualify for the differential diagnosis of glioblastoma variants. The tumors were also screened for mutation of TP53, IDH1, IDH2, and β-catenin, using single strand conformation polymorphism-based and sequencing assays, and were analyzed for c-myc/N-myc gene copy numbers with a quantitative polymerase chain reaction-based method. The strand conformation polymorphism-based mutational analysis showed that 5 tumors harbored TP53 mutations. In 2 cases, a mutation at codon 132 of the IDH1 gene was also found. No mutations of the β-catenin or IDH2 genes were identified. No cases presented c-myc or N-myc amplifications. Only 1 case presented overexpression of epidermal growth factor receptor. In conclusion, our data show a high incidence of TP53 mutations in this group of tumors and show, in comparison with pediatric s-PNET, the absence of amplification of the c-myc/N-myc genes, indicating that s-PNET in adult patients may represent a specific subset of tumors among CNS-PNETs.

Supratentorial primitive neuroectodermal tumor in an adult: a case report and review of the literature

“…Furthermore, Gessi et al . have shown that a high incidence of TP53 mutations and the absence of amplification of the c-myc/N-myc genes in adult sPNET, in comparison to pediatric PNET, suggest that adult sPNET should be an independent subset of tumors among CNS-PNETs [3]. …”

“…On magnetic resonance imaging (MRI), these tumors appear as well-delimited, inhomogeneous, and variably contrast-enhanced lesions. Furthermore, on T1-weighted images, PNETs appear hypointense, and on T2-weighted images they appear hyperintense [3-6]. …”

Meningeal Ewing Sarcoma/Peripheral PNET: Clinicopathological, Immunohistochemical and FISH study of four cases

“…Primitive neuroectodermal tumor (PNET)/Ewing Sarcoma (ES) is a rare family of malignancies in the CNS, always creating diagnostic challenges in CNS tumors . Unlike the central type PNET, which accounts for about 2.5% of brain tumors in children and about 0.46% in adults, the ES/pPNET in CNS also occurs with intracranial/intraspinal meningeal extension, characterized by fusion of the EWSR1 gene (22q12) with a member of the ETS gene family, including FLI1, ERG, ETV1, EIAF and so on, showing different histogenesis, molecular characteristics, and better clinical prognosis . The ES/pPNET is rather uncommon in the CNS and we could only identify four cases in the archives of our department over 6 years.…”

“…1 Unlike the central type PNET, which accounts for about 2.5% of brain tumors in children and about 0.46% in adults, the ES/pPNET in CNS also occurs with intracranial/intraspinal meningeal extension, characterized by fusion of the EWSR1 gene (22q12) with a member of the ETS gene family, including FLI1, ERG, ETV1, EIAF and so on, showing different histogenesis, molecular characteristics, and better clinical prognosis. 2,[4][5][6][7][8][9]14,[23][24][25] The ES/pPNET is rather uncommon in the CNS and we could only identify four cases in the archives of our department over 6 years. Therefore, it is important to investigate the clinical pathological features and its possible differential diagnosis for the selection of proper therapy and accurate assessment of its prognosis.…”

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: Case report and review of the literature

“…They commonly occur in low grade gliomas and secondary GBMs, rarely in primary GBMs. IDH1 mutation have been observed also in a small percentage of adult PNETs (15)(16)(17). The PNET components are explained by two main hypotheses (8): PNET-like foci arise from pre-existing gliomas, most often a secondary GBM (neuroblastic or neuronal metaplasia) and the clonal expansion of tumour stem cells or progenitor cells resulting in PNET-like nodules (7,15,18).…”