BACKGROUND: A recent randomized study conducted on newly diagnosed glioblastoma (GBM) patients demonstrated that concomitant and adjuvant temozolomide added to standard radiotherapy had a survival advantage compared with radiotherapy alone. The overall survival benefit of this aggressive treatment, however, was attenuated in older or poor performance status patients. The aim of the present study was to verify the activity and the toxicity of temozolomide administration concurrent and adjuvant to radiotherapy as first‐line treatment for elderly GBM patients, and to explore correlations between clinical outcome and O6 methylguanine‐DNA methyltransferase (MGMT) promoter methylation status. METHODS: Newly diagnosed GBM patients ≥65 years were considered eligible. Treatment comprised radiotherapy (60 Gy in 30 fractions over 6 weeks) plus continuous daily temozolomide (75 mg/m2/day), followed by 12 maintenance temozolomide cycles (150 mg/m2 once a day for 5 consecutive days every 28 days) if MRI showed no enhancement suggesting a tumor; otherwise, chemotherapy was delivered until complete response or unequivocal progression. RESULTS: A total of 58 patients (34 males; median age, 68 years; range, 65‐82 years) were enrolled. Sixteen patients (43%) presented MGMT promoter methylated and 21 unmethylated (57%) status. The median progression‐free survival and median survival time (MST) were 9.5 months (95% confidence interval [CI], 8.6‐10.5) and 13.7 months (95% CI, 10‐17.3 months), respectively. Mental status deterioration grade 3‐4 was detected in 25% of patients. Leukoencephalopathy was diagnosed in 10% of patients. CONCLUSIONS: The overall and progression‐free survival of patients given concomitant and adjuvant temozolomide are greater than in those given radiotherapy alone; however, this regimen incurs a greater deterioration in mental status. Further randomized trials should, therefore, be conducted to investigate the efficacy and against the toxicity of this regimen as first‐line therapy in patients with GBM. Cancer 2009. © 2009 American Cancer Society.

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

This study demonstrates that mucins that had spilled out from the cyst caused the granulomatous reaction. Using computed tomography, magnetic resonance imaging, and gross inspection, distinction between granulomatous hypophysitis and pituitary adenoma was virtually impossible. Nevertheless, a granulomatous reaction of the pituitary gland should be suspected in a case of a sellar mass having a cystic area. In such cases, intraoperatory diagnosis on frozen sections is mandatory because adoption of a conservative treatment allows preservation of the gland.

BACKGROUND AND PURPOSE:A growing body of evidence suggests the involvement of the brain in FM. The purpose of this proton MRS study was to test the hypothesis that there are metabolic alterations in some brain regions processing pain (VLPFC and thalamus) in patients with FM compared with HC.

BACKGROUND AND PURPOSE:Little is known about the metabolic properties of brain edema associated with tumors. This work was conducted on the basis of the assumption that, in the presence of intra-axial and extra-axial brain tumors, the white matter involved by the edema is a site of metabolic change that involves the structure of the myelin sheath.

The spectrum of corticotroph cell adenomas is very wide. Though rarely, silent corticotroph cell adenomas (SCA) may transform into corticotroph cell adenomas associated with Cushing's disease (CD). The aim of the study was to investigate the role of prohormone convertase 1/3 (PC1/3) in the transformation of SCA into CD. We reviewed the records of 1259 consecutive endoscopic endonasal procedures for pituitary adenomas from 1998 to 2013. Of these, 132 were CD and 44 were SCA. During the follow-up, three patients with SCA showed a clear transformation from SCA into CD and underwent surgery once again to remove the recurrent tumour. The PC1/3 expression was analysed by both immunohistochemistry and quantitative real time-polymerase chain reaction (qRT-PCR) in primary and recurrent tumours. The immunohistochemical PC1/3 expression was negative or weak in the three patients in the initial phase of SCA, while a strong expression was observed in the majority of neoplastic cells in tissue specimens obtained from the same three patients at the time of recurrence as CD. The immunohistochemical PC1/3 expression showed a strict correlation with the PC1/3 levels obtained by qRT-PCR. In 14 cases of SCA with no change of phenotype during the follow-up, the immunohistochemical PC1/3 expression was low and strictly associated with the level of PC1/3 obtained by qRT-PCR both in primary (14/14 cases) and in recurrent tumours (4/4 cases). Our study provides insight into the crucial role of the PC1/3 protein in the transformation of phenotype from SCA to CD.

Aims De‐differentiated chordoma is an uncommon and incompletely characterised aggressive neoplasm. Only a few cases originating from the skull base have been reported. Methods and results All consecutive cases of skull‐base de‐differentiated chordomas treated surgically in a referral centre from January 1990 to June 2019 were retrospectively evaluated to assess peculiar pathological, radiological and clinical features. Patient data were retrieved from paper and electronic records. Six cases (two male, four female; mean age at surgery = 46 years, range = 35–64), treated surgically at our institution were identified. Transformation to de‐differentiated chordomas occurred after radiation therapy in three cases (mean = 13.6 years after treatment, range = 5–25), two during tumour progression, while one was de‐novo. Magnetic resonance imaging and surgical examination revealed the presence of two different tumour components, corresponding to the conventional and de‐differentiated portion on histological examination. The de‐novo case presented a PIK3CA mutation. DNA methylation analysis revealed consistent epigenetic changes in TERT, MAGEA11 and UXT. Prognosis was poor, as five of six patients died after surgery and radiation therapy, with a mean overall survival of 29 months (range = 11–52). Conclusions Skull‐base de‐differentiated chordomas are extremely rare and aggressive neoplasms with characteristic magnetic resonance imaging, surgical and histological features. Therefore, an early and accurate histological diagnosis is of paramount relevance. Molecular analysis appears promising to define mechanisms involved in tumour de‐differentiation.

OM is the same disease in adulthood and childhood, even if in adults the MR imaging findings are negative. In the authors' opinion, OM should be classified as migraine.