Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis. The gene responsible for NBCCS is PTCH1. The development of meningioma in NBCCS patients is a rare event. Here, we report two cases of NBCCS in which meningiomas did develop. The first patient carried a germline mutation in one allele of PTCH1, c.290dupA (p.N97KfsX43). In addition, the meningioma sample carried a somatic mutation, c.307delG (p.Val103LeufsX15), in the other allele of the same gene, suggesting a second hit. This is the first case of NBCCS-associated meningioma explained by the standard two-hit hypothesis. The second patient had a germline nonsense mutation in the SUFU gene, c.550C>T (p.Q184X). SUFU is located downstream of PTCH1 in the sonic hedgehog signaling pathway. This is the second time a germline mutation in SUFU has been found to cause NBCCS. Together with the previous report describing three cases of non-NBCCS medulloblastoma carrying a germline mutation in this gene, individuals with a SUFU germline mutation are expected to have a markedly high risk of developing medulloblastoma and probably meningioma.

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.

The frequency and clinical features of Epstein-Barr virus (EBV)-associated primary central nervous system lymphoma (PCNSL) in elderly patients were investigated in this study. Thirty-three PCNSL cases were enrolled in the retrospective study. Biopsies were performed, and tissue was embedded in paraffin and sectioned. In-situ hybridization of EBV-encoded small RNAs was then conducted. Specimens were scored as having one of three possible results: negative (no EBV-positive cells), slightly positive (<50% EBV-positive cells), and strongly positive (>50% EBV-positive cells). Fifteen cases were negative for EBV expression. Sixteen cases were slightly positive, and two cases (68 and 79 years of age) were strongly positive. The incidence of strongly positive EBV expression in PCNSL was 6.1%. The incidence of strongly positive EBV expression in PCNSL patients ≥65 years of age was 13%. Median survival time differed significantly among PCNSL patients treated with high-dose methotrexate and radiotherapy. Importantly, the strongly EBV-positive PCNSL cases had the worst outcomes, and the EBV-negative PCNSL cases had the best outcomes. These results suggest that EBV infection may affect the treatment outcome of PCNSL. In the future, examination of EBV expression in PCNSL patients who receive individualized treatment may be useful.

We describe the clinicopathological features of 25 brainstem gliomas (BSGs). Twenty BSGs located in the pons and were all in children. Four BSGs located in the medulla oblongata were in 2 children and 2 adults. One (in a child) was located in the midbrain. Radiological findings on MR images were low-intensity on T1 weighted images and high-intensity on T2 weighted images. Mean survival when pontine glioma was treated by radiotherapy and/or use of temozolomide was 14 months, although 4 patients (3 cervicomedullary types and one focal type arising from midbrain) are alive. Follow up was from 5 months to 6 years. Histopathological features of 10 cases of the diffuse type were: 4 grade II astrocytomas, 4 grade III astrocytomas, and 2 glioblastomas. MIB-1 index was from 0.8 to 38 %. P53 was positive for 80 % of 15 tumors and there were no negative results. MGMT was positive in 60 % of 15 tumors and negative in 12.4 %. IDH1 was negative in 61.6 %. There was no positive result for IDH1 in this study. Thus, our histopathological results were indicative of high p53 immunoreactivity and no IDH1 immunoreactivity related to secondary malignant change.

A 55-year old female was referred to the Department of Neurosurgery, Kitasato Hospital, because of a hearing impairment. Neuroimaging revealed a typical meningioma attached to the falx in the right frontal region. During surgery, an encapsulated, circumscribed, reddish-gray, slightly hard tumor attached to the falx was completely removed by an interhemispheric approach. On light microscopy, many of the tumor cells contained eosinophilic inclusions with single or multiple vacuoles that displaced the cytoplasm. The nuclei of the tumor cells were eccentric. There were no signs of malignancy in the specimen. Electron microscopy revealed that most of the eosinophilic inclusions were composed of filaments measuring 12 nm in diameter. There have been several reports of benign meningiomas with eosinophilic inclusions composed of intermediate filaments. The microscopic differences between these types of tumor and rhabdoid meningiomas are very subtle, and it is important the two types of tumors are not confused. Benign meningiomas with eosinophilic inclusions comprising intermediate filaments, for example the tumor described in this report, have been diagnosed as granulofilamentous meningiomas, which is a subtype of benign meningioma.