HP is not extremely rare. ANCA-related HP is the most frequent form, followed by IgG4/MFS-related HP. Both forms have unique features, which may help to differentiate background causes.

Gene rearrangement in the form of an intragenic deletion is the primary mechanism of oncogenic mutation of the epidermal growth factor receptor (EGFR) gene in gliomas. However, the incidence of platelet-derived growth factor receptor-a (PDGFRA) gene rearrangement in these tumors is unknown. We investigated the PDGFRA locus in PDGFRA-amplified gliomas and identified two rearrangements, including the first case of a gene fusion between kinase insert domain receptor (KDR) (VEGFRII) and the PDGFRA gene, and six cases of PDGFRA D8, 9 , an intragenic deletion rearrangement. The PDGFRA D8, 9 mutant was common, being present in 40% of the glioblastoma multiformes (GBMs) with PDGFRA amplification. Tumors with these two types of PDGFRA rearrangement displayed histologic features of oligodendroglioma, and the gene products of both rearrangements showed constitutively elevated tyrosine kinase activity and transforming potential that was reversed by PDGFR blockade. These results suggest the possibility that these PDGFRA mutants behave as oncogenes in this subset of gliomas, and that the prevalence of such rearrangements may have been considerably underestimated.[Keywords: Copy number alteration; glioma; PDGFRA gene rearrangement; receptor tyrosine kinase] Supplemental material is available at http://www.genesdev.org.

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We performed a pathological study to identify the locus of production of protoporphyrin IX (PPIX) in human metastatic brain tumors. Patients with metastatic brain tumors (n = 11) received 1 g of 5-aminolevulinic acid (5-ALA) perorally 2 h before undergoing surgery. The target region was exposed to laser light with a peak wavelength of 405 +/- 1 nm and an output of 40 mW. Tissue samples from the tumor bulk and surrounding areas were examined by histological and fluorescence methods. Of the 11 tumors, 9 manifested PPIX fluorescence in the tumor bulk and peritumoral brain tissue. Our findings indicate that PPIX fluorescence can be observed in peritumoral edematous areas that are free of neoplastic cells, because PPIX produced by neoplastic cells leaks into the surrounding edematous area.

The response of nonfluorescing infiltrating tumors that had been exposed to 5-aminolevulinic acid and irradiated using a laser at a wavelength of 405 nm was analyzed intraoperatively using spectroscopy. Histological analyses demonstrated that neoplastic cells were present in the tissue region that displayed a peak at 636 nm, whereas no neoplastic cells were present in the region that exhibited only the excitation light peak. The authors conclude that the intraoperative use of laser spectroscopy can allow the diagnosis of infiltrating tumor and the detection of boundaries of the infiltrate when standard fluorescence techniques fail.

The aim of this study is to review the different histological and clinical characteristics of glioblastoma multiforme (GBM) with and without cysts (cystic and noncystic GBM, respectively). Thirty-seven GBM were collected; these were tumors for which more than 80% of the volume was surgically resected, including a portion of the peripheral parenchyma of the brain. Based on preoperative magnetic resonance (MR) imaging studies, tumors were tentatively classified as cystic GBM if more than 50% of their volume appeared to be liquid; otherwise, they were considered to be noncystic GBM. Tumor volumes were estimated from contrast-enhanced T1-weighted MR images. Edema was deduced from the maximum width of contrast-enhanced edges. Peritumoral pathological analysis showed distinct margins, indicating little or no infiltration of tumor cells into white matter. Five cases were classified as cystic and 32 were noncystic GBMs. There was a statistically significant difference in age (Mann-Whitney U test; P < 0.05) between the patients with cystic tumors (median, 44 years; range, 26-59 years) and those with noncystic tumors (median, 54 years; range, 26-81 years). Four of the cystic tumors and eight of the noncystic tumors were more than 5 cm in maximum diameter. Cystic GBMs had a well-defined tumor interface and less than 2-cm-thick peritumoral edema compared to the noncystic GBMs (Fisher's exact test; P < 0.05). For patients with cystic GBMs, median survival time after surgery was 19.8 months and the 2-year survival rate was 50%. Patients with noncystic GBMs had a median survival time of 12.8 months and a 2-year survival rate of only 17%. Median time to tumor recurrence was 13.3 months for patients harboring cystic GBMs and 8.5 months for those with noncystic GBMs (log-rank test; P < 0.05). Thus, the prognosis for cystic GBM was significantly better than that for noncystic GBM, possibly because cystic GBMs showed comparatively little infiltration of the peritumoral brain parenchyma.

This study is a histological and clinical investigation of four cases of cerebellar glioblastoma, a rare tumor. The cases included three males and one female, from 33 to 67 years in age (mean 49 years). Tumor resection, postoperative irradiation and chemotherapy were performed in all cases. Two patients died of local tumor recurrence after 14 and 27 months. Another patient relapsed after 10 months; however, after additional tumor resection and second line chemotherapy, she remains disease-free 41 months after the initial treatment. The fourth patient has not relapsed in the 6 months since initial treatment. The histopathology of all cases was glioblastoma with pseudopalisading necrosis. However, low-grade glioma histopathology was found in three patients. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These adult cerebellar glioblastoma cases had similar clinical and pathological characteristics, and had different characteristics compared with supratentorial glioblastomas.

Key words: MGMT; real-time RT-PCR; ACNU; gliomaNitrosoureas are alkylating agents that cause cell death by binding to DNA. Among nitrosoureas, 1-(4-amino-2-methyl-5-pyrimidynyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) is widely used in Japan to treat gliomas because of its ability to permeate the blood-brain-barrier and excellent clinical effects in combination with radiation and interferon (IFN)-␤. [1][2][3] Drug-resistance genes are some of the most important elements of tumors themselves in determining drug-resistance, 4 and O 6 -methylguanine-DNA methyltransferase (MGMT) is a drug-resistance gene for nitrosoureas. 5,6 The cross-linking of doublestranded DNA by alkylating agents is inhibited by the cellular DNA-repair protein MGMT. MGMT rapidly reverses alkylation at the O 6 position of guanine, thereby averting lethal cross-linking. 7 This is the mechanism by which MGMT induces resistance to alkylating agents such as ACNU.Protocol studies for malignant gliomas have not provided encouraging therapeutic results because of the heterogeneity and various drug-sensitivities of the tumors. 8,9 Individualization of glioma therapy is recommended. We carried out a new adjuvant therapy that was individualized based on the results of the reverse transcription-polymerase chain reaction (RT-PCR) for MGMT to treat malignant gliomas. 2 Our preliminary individual adjuvant therapies (IAT) based on RT-PCR results regarding MGMT expression seemed to be more effective than conventional therapies for malignant gliomas.The level of MGMT varies widely according to the type of tumor, and even varies among tumors of the same histological classification. 5,10 Approximately 30 -50% of gliomas lack MGMT. 11 The fact that more than 50% of gliomas express MGMT limits the indications for ACNU. In our preliminary IAT, platinum (Pt)-compounds were used instead of ACNU even though Ptcompounds had not been accepted as being effective in gliomas. 12,13 To ensure IAT for gliomas, quantitative evaluation is needed for a higher initial response and prolongation of survival.We carried out the present study to determine more appropriate indications for the use of ACNU in gliomas. Real-time quantitative RT-PCR was used to re-evaluate the treated gliomas. MATERIAL AND METHODS Real-time quantitative RT-PCRIn 100 frozen sample of neuroepithelial tumors (19 low-grade neuroepithelial tumors, 28 Grade III gliomas, 41 glioblastomas, and 12 medulloblastomas), MGMT was quantitated by real-time quantitative RT-PCR using SYBR Green dye. RT-PCR was basically carried out as described previously. 14 -16 Briefly, total RNA was extracted from frozen tissue specimens weighing about 1 g, which had been homogenized using a glass Teflon homogenizer, via the guanidinium thiocyanate-phenol-chloroform single-step extraction method with Isogen (Nippon Gene, Toyama, Japan). 17 After ethanol precipitation, about 100 g of total RNA was extracted. Forty microliters of complementary deoxyribonucleic acid (cDNA) solution was synthesized from 2 g of total RNA wi...