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Radiation-induced gliomas (RIGs), which occur in a previously irradiated region of the original tumor, represent a rare but well-characterized clinical entity. Integrated diagnosis of the tumor was made as diffuse pediatric-type high-grade glioma, H3-wild type, and IDH-wild type,[[8]] corresponding to RIG. RIGs were traditionally noted to consist of a heterogeneous population and could be diagnosed by exclusion of other tumors.[1] Recent reports demonstrated that RIGs harbor unique molecular features, including a homologous epigenetic profile with sporadic GBM RTK1 tumors.[[2]] Methylation profiling would thus be recommended for the diagnosis of "molecularly defined" RIGs. [Extracted from the article]

Temozolomide ( TMZ) is an oral alkylating agent which is widely used in the treatment of glioblastoma ( GBM) and is composed of astrocytic and/or oligodendroglial tumors, and the evaluation of O6-methylguanine DNA methyltransferase ( MGMT) expression is important to predict the response to TMZ therapy. In this study, we conducted immunohistochemical analysis of 117 cases of Japanese GBM including 19 cases of GBM with oligodendroglioma component ( GBMO), using a scoring system for quantitative evaluation of staining intensity and proportion of MGMT, and performed survival analysis of these patients. Immunohistochemically, 55 cases (47%) were positive for MGMT with various intensities and proportions (total score ( TS) ≥ 2), while 62 cases (53%) were negative ( TS = 0). The distribution of MGMT expression pattern was not affected by any clinicopathological parameters such as the histological subtype ( GBM vs. GBMO), age and gender. The survival analysis of these patients revealed that the minimal expression of MGMT ( TS ≥ 2) was a significant unfavorable prognostic factor ( P < 0.001) as well as resectability ( P = 0.004). Moreover, multivariate analysis showed that minimal MGMT expression in GBM was the most potent independent predictor for progression free survival ( P < 0.001) and also overall patient survival ( P < 0.001). This is the first report employing the scoring system for both staining intensity and proportion to evaluate immunohistochemical MGMT expression in GBM. In addition, our results emphases the clinicopathological values of the immunohistochemical approach for MGMT expression in glioma patients as a routine laboratory examination. [ABSTRACT FROM AUTHOR]

Pineal parenchymal tumors (PPTs) are rare neoplasms which occupy less than 1% of primary CNS tumors. Because of their rare incidence, previous reports on PPTs are limited in number and the useful molecular markers for deciding histological grading and even selecting chemotherapy are undetermined. In this study, we conducted immunohistochemical analysis of 12 PPT specimens, especially for expression of O6-methylguanine DNA methyltransferase (MGMT) to assess whether temozolomide (TMZ) could serve as a possible alternative therapy for PPTs. We analyzed 12 PPTs, consisting of three pineocytomas, six PPTs of intermediate differentiation (PPTIDs), and three pineoblastomas. Immunohistochemical analysis was performed using antibodies against MGMT, synaptophysin, neurofilament protein (NF), p53, and neuronal nuclear antigen (NeuN). Immunohistochemically, 11 out of 12 cases were positive for MGMT. The mean MIB-1 labeling index was less than 1% in pineocytoma, 3.5% in PPTID, and 10.5% in pineoblastoma. All 12 cases were positive for synaptophysin and 11 cases, except one PPTID case, showed positive for NF. Nuclear staining of NeuN was negative in all cases although cytoplasmic staining of NeuN was observed in five cases. No case was positive for p53. Eleven out of 12 cases of PPTs demonstrated MGMT expression, suggesting chemoresistancy to TMZ treatment. This is the first report showing MGMT expression in PPTs. In addition, MIB-1 labeling index correlated with WHO grade, although the immunoreactivity of synaptophysin, NF, NeuN and p53 did not correlate with the histological grade. [ABSTRACT FROM AUTHOR]

Most cases of dementia with Lewy bodies (DLB) follow a chronic course. However, some cases of rapidly progressive dementia (RPD) are difficult to distinguish from other diseases. Herein, we report how to differentiate DLB presenting with RPD from other diseases and its pathological features, with examples from our own experience. A 70‐year‐old man with RPD and psychiatric symptoms, including hallucinations and delusions, was transferred to our hospital. We suspected Creutzfeldt–Jakob disease (CJD), but disease‐specific tests were all negative. The patient was treated with corticosteroids on the suspicion of an autoimmune condition; however, his symptoms did not improve. Based on the results of nuclear medicine and other tests, we suspected DLB and administered anti‐Parkinsonian drugs; however, they were ineffective, and the patient died. Brain autopsy revealed extensive deposits of Lewy bodies, which were pathologically diagnosed as DLB. Additionally, extensive deposition of senile plaques was observed; however, neurofibrillary tangles (NFTs) were not prominent. DLB generally presents as a chronic disease. However, some patients with DLB present with RPD; therefore, the differential diagnosis of other diseases, such as CJD, is very important. In addition, although this case was not diagnosed with Alzheimer's disease (AD) due to the lack of NFTs, extensive amyloid deposition was observed in the brain tissue. Previous reports have described cases of RPD with amyloid deposition alone, and in this case too, it is suggested that amyloid deposition might have had a strong influence on the clinical course of RPD. [ABSTRACT FROM AUTHOR]

Clinical diagnosis of progressive supranuclear palsy (PSP) is difficult due to various phenotypes. Neuropathologically, PSP is defined by neuronal loss in the basal ganglia and brainstem with widespread occurrence of neurofibrillary tangles (NFTs) and accumulation of phosphorylated tau protein in neurons and glial cells in the brain. We previously identified the point mutation p.Pro3866Ala in the Bassoon (BSN) gene in a Japanese family with PSP‐like syndrome. We newly detected BSN mutations in two autopsied PSP cases carrying p.Thr2542Met and p.Glu2759Gly, respectively. The case with p.Thr2542Met mutation showed neurological symptoms including behavioral abnormalities, cognitive dysfunction, and parkinsonism. Brain magnetic resonance imaging (MRI) showed atrophy of the midbrain tegmentum and hippocampus. Pathologically, moderate to severe loss of neurons with gliosis was also found in the substantia nigra, and there was an almost complete loss of neurons with gliosis in the transitional zone of the cornu ammonis (CA) 1 region to the subiculum. NFTs were observed in the globus pallidus, subthalamic nucleus, substantia nigra, and CA1. 4R tau‐dominant tauopathy was detected. The case with p.Glu2759Gly mutation showed neurological symptoms, including right‐dominant motor impairment, right limping gait, postural instability, and cognitive dysfunction. Brain MRI showed mild atrophy of the midbrain tegmentum and left‐dominant parietal lobe atrophy. Pathologically, NFTs were detected in the globus pallidus, subthalamic nucleus, substantia nigra, thalamus, putamen, and brainstem tegmentum. Most neurons were immunopositive for four‐repeat tau, whereas only a few of them harbored three‐repeat tau‐positive NFTs in the hippocampus. We showed the results of a pathological study of PSP cases with BSN mutations; these were two new cases. The clinical phenotypes were similar to the first case in the point of neurological symptoms. Accumulation of four‐repeat tau was dominant. Further autopsies of BSN mutation cases and further elucidation of the molecular biological mechanism are desirable. [ABSTRACT FROM AUTHOR]