Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials.

Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In this study, we performed a comprehensive clinical, pathological, and molecular analysis of 97 cases of these rare brain neoplasms, including genome-wide DNA methylation and copy number profiling of 41 tumors. We identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. As such, future WHO classification schemes should consider lumping these variants into a single diagnostic category, such as embryonal tumor with multilayered rosettes (ETMR). We recommend combined LIN28A immunohistochemistry and FISH analysis of the 19q13.42 locus for molecular diagnosis of this tumor category. Recognition of this distinct pediatric brain tumor entity based on the fact that the three histological variants are molecularly and clinically uniform will help to distinguish ETMR from other embryonal CNS tumors and to better understand the biology of these highly aggressive and therapy-resistant pediatric CNS malignancies, possibly leading to alternate treatment strategies.

In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports.

Glioblastoma (GBM) and meningothelial meningioma (MM) are the most frequent malignant and benign brain lesions, respectively. Mechanical cues play a major role in the progression of both malignancies that is modulated by the occurrence of aberrant physical interactions between neoplastic cells and the extracellular matrix (ECM). Here we investigate the nano-mechanical properties of human GBM and MM tissues by atomic force microscopy. Our measures unveil the mechanical fingerprint of the main hallmark features of both lesions, such as necrosis in GBM and dural infiltration in MM. These findings have the potential to positively impact on the development of novel AFM-based diagnostic methods to assess the tumour grade. Most importantly, they provide a quantitative description of the tumour-induced mechanical modifications in the brain ECM, thus being of potential help in the search for novel ECM targets for brain tumours and especially for GBM that, despite years of intense research, has still very limited therapeutic options.

Radiotherapy is the only treatment definitely indicated for diffuse pontine gliomas (DIPG). Findings on the role of EGFR signaling in the onset of childhood DIPG prompted the use of nimotuzumab, an anti-EGFR monoclonal antibody. Assuming a potential synergy with both radiotherapy and vinorelbine, a pilot phase 2 protocol was launched that combined nimotuzumab with concomitant radiation and vinorelbine. An amendment in July 2011 introduced re-irradiation at relapse. The primary endpoint for first-line treatment was objective response rate (CR + PR + SD) according to the RECIST. This report concerns the outcome of this strategy as a whole. Vinorelbine 20 mg/m(2) was administered weekly, with nimotuzumab 150 mg/m(2) in the first 12 weeks of treatment; radiotherapy was delivered from weeks 3 to 9, for a total dose of 54 Gy. Vinorelbine 25 mg/m(2) and nimotuzumab were given every other week thereafter until the tumor progressed or for up to 2 years. Re-irradiation consisted of 19.8 Gy, fractionated over 11 days. Baseline and latest MRIs were assessed blindly by an outside neuroradiologist. Twenty five children (mean age 7.4 years) were enrolled as of August 2009 (median follow-up 29 months). A response was observed in 24/25 patients (96 %). The nimotuzumab/vinorelbine combination was very well tolerated, with no acute side-effects. Eleven of 16 locally-relapsing patients were re-irradiated. One-year PFS and OS rates were 30 ± 10 % and 76 ± 9 %, respectively; 2-year OS was 27 ± 9 %; the median PFS and OS were 8.5 and 15 months, respectively. This strategy generated interesting results and warrants further investigation.

Astroblastoma is one of the rarest tumors of the central nervous system (CNS), and its classification, histogenesis, diagnosis and therapeutic management are still being debated. The typical histopathological appearance is the perivascular, astroblastic pseudorosette, which is however present in other CNS tumors. To clarify the clinical, radiological, histopathological, prognostic and therapeutic characteristics, which have been treated only recently and are not well established yet due to the rarity of this tumor, six cases of histologically proven astroblastoma were retrospectively analyzed in light of more pertinent literature and paying special attention to therapeutic remarks. Between 1996 and 2005, six patients with cerebral astroblastoma were surgically treated at the Department of Neurosciences-Neurosurgery of Sapienza University in Rome. In three cases the lesion was termed low-grade astroblastoma, and high grade in the other three, according to current standard parameters. Median age of the six patients was 36 years. The time to diagnosis ranged from 1 week to 18 months. The radiological and anatomopathological features of this lesion are described. Surgical removal was total in four cases and subtotal in two. All patients received radiotherapy: two also had chemotherapy with temozolomide (TMZ). The three patients with low-grade astroblastoma are still alive today after a follow-up of 2, 5 and 19 years, respectively. Of the three patients with high-grade lesions, one is still alive after a 7-year follow-up, while the other two survived for 17 months (progression time 15 months) and 35 months (progression-reoperation time 23 months), respectively. Conclusions radical surgical resection is the treatment of choice for astroblastomas. Radiotherapy may play an adjuvant role in the treatment of high-grade lesions. The role of chemotherapy is still very debatable. We propose an aggressive standardized treatment for those lesions that meet anaplastic criteria, owing to their postulated glial origin and the propensity to have aggressive courses, and we advocate the use of a safe adjuvant chemotherapeutic regimen with TMZ, used concomitantly and subsequently to radiotherapy, especially for the high-grade astroblastoma cases. Multicenter studies, taking into account molecular biological findings, are necessary to define a common therapeutic strategy for astroblastomas.

Summary Expression of the autoimmune regulator gene (AIRE) and the presence of CD25+ /forkhead box p3 (FoxP3) + T regulatory (Treg) cells were investigated in histologically normal adult thymi and in thymomas using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). In the normal thymus staining for AIRE was detected in the nucleus of some epithelial-like cells located in the medulla; in thymomas AIRE-positive cells were extremely rare and could be detected only in the areas of medullary differentiation of two B1 type, organoid thymomas. RNA was extracted from 36 cases of thymoma and 21 non-neoplastic thymi obtained from 11 myasthenic (MG + ) and 10 non-myasthenic (MG -) patients. It was found that AIRE is 8·5-fold more expressed in non-neoplastic thymi than in thymomas (P = 0·01), and that the amount of AIRE transcripts present in the thymoma

The majority of glioblastomas develop rapidly with a short clinical history (primary glioblastoma IDH wild-type), whereas secondary glioblastomas progress from diffuse astrocytoma or anaplastic astrocytoma. IDH mutations are the genetic hallmark of secondary glioblastomas. Gliosarcomas and giant cell glioblastomas are rare histological glioblastoma variants, which usually develop rapidly. We determined the genetic patterns of 36 gliosarcomas and 19 giant cell glioblastomas. IDH1 and IDH2 mutations were absent in all 36 gliosarcomas and in 18 of 19 giant cell glioblastomas analyzed, indicating that they are histological variants of primary glioblastoma. Furthermore, LOH 10q (88%) and TERT promoter mutations (83%) were frequent in gliosarcomas. Copy number profiling using the 450k methylome array in 5 gliosarcomas revealed CDKN2A homozygous deletion (3 cases), trisomy chromosome 7 (2 cases), and monosomy chromosome 10 (2 cases). Giant cell glioblastomas had LOH 10q in 50% and LOH 19q in 42% of cases. ATRX loss was detected immunohistochemically in 19% of giant cell glioblastomas, but absent in 17 gliosarcomas. These and previous results suggest that gliosarcomas are a variant of, and genetically similar to, primary glioblastomas, except for a lack of EGFR amplification, while giant cell glioblastoma occupies a hybrid position between primary and secondary glioblastomas.