Malignant Gliomas as Second Neoplasms in Pediatric Cancer Survivors: Neuropathological Study

Abstract

This study presents a unique series of malignant supratentorial gliomas in children previously cured from non-CNS primary cancer. On neuroimaging these tumors were not specific, so the patients were suspected of cerebral recurrence of their primary neoplasm: leukemia in four children and sarcoma in one child. Histologically, the group contained four glioblastomas and one anaplastic astrocytoma. Three patients underwent neurosurgical resection, while the other two underwent stereotactic diagnostic biopsy only. Despite combined oncological treatment, four children died during 20 months, and only one glioblastoma patient continued to live for another twelve years. Microscopically, the neoplasms consisted of small cells with some morphologic features of astrocytic lineage, having scanty or prominent processes. Microvascular proliferation and focal or diffuse necrosis were encountered in four cases. The GFAP reactivity in neoplastic cells was low or nil, together with the expression of Olig2, vimentin, and nestin. In two cases a subpopulation of synaptophysin-positive cells was present. Molecular immunohistochemical profiling revealed the expression of phosphorylated forms of PI3Kp110 and AKT, in parallel to a strong PTEN and p53 positivity. The tumors were of IDH1R132H-wild type and immunoreactive for ATRX, HER3, and EGFR. Secondary malignant gliomas in pediatric cancer survivors pose a diagnostic challenge. The present study shows that these tumors are of IDH wild type, PI3K/AKT-activated, having no PTEN and EGFR mutations. Therefore, the biopsy of brain tumors in such patients is crucial both for accurate diagnosis and material preservation for molecular typing.

Nasal Drug Delivery of Anticancer Drugs for the Treatment of Glioblastoma: Preclinical and Clinical Trials

“…Malignant brain tumors are devastating diseases with high morbidity and mortality in adults. In children, they represent the second leading cause of cancer related deaths [1,2]. Glioblastoma multiforme (GBM) is the most common and the most lethal malignant primary brain tumor in adults.…”

Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers

“…Germline mutations, such as in Li Fraumeni Syndrome, are associated with increased cancer risk and increased toxicity from DNA damaging agents [101] . However, somatic TP53 mutations or epigenetic silencing have been associated with increased rates of relapse, with enrichment in these tumors, and with worse prognosis both at diagnosis and relapse, including in glioma [102,103] , neuroblastoma [104][105][106][107] , and leukemia [108,109] . Mutations in other components of the DNA repair and cell cycle pathways in refractory pediatric cancers, including ATM, ATR, PTEN, and CHEK1, have also been associated with poor prognosis, presumably through avoidance of cell death [110][111][112] .…”

Clinical Characteristics, Treatment Outcomes, And Genetic Alterations of Radiation-Induced Gliomas

“…[6] Moreover, there have been few reports that investigated genetic alterations of RIG. [8][9][10][11][12][13][14] In this study, we investigated the clinical characteristics, treatment outcomes, and genetic alterations of 11 patients with RIG with the aim to identify the optimal follow-up period from the treatment of primary disease, therapeutic strategy, molecular characteristics and their clinical impact of RIG.…”