The aim of this study was to review recent advances in genomic analysis and explore possibilities in genomic medicine for benign brain tumors, particularly craniopharyngioma, meningioma, and schwannoma. Craniopharyngioma includes the adamantinomatous and papillary subtypes. Recent genetic analysis has demonstrated that the two subtypes differ not only in clinicopathological features but also in molecular oncogenesis. Adamantinomatous craniopharyngioma tumors can be distinguished by the frequent mutation of the β-catenin gene (mutations of CTNNB1), whereas the papillary subtype is characterized by the V600E mutation of the BRAF gene activating the MAP kinase pathway (MAPK). A clinical trial currently underway for the papillary subtype is investigating the use of a MAPK inhibitor. Meningiomas have exhibited frequent chromosomal alterations, including mutations at the NF2 locus. Recent studies demonstrated that driver genes such as TRAF7, KLF4, AKT1, and SMO are mutated in 40% of sporadic meningiomas. Umbrella trials for SMO, AKT1, and NF2 mutations are currently being conducted. The novel fusion gene SH3PXD2A-HTRA1, which activates the MAPK pathway, has been associated with sporadic schwannoma. Anti-angiogenic therapy with bevacizumab has been effective for NF2-associated schwannoma. Clinical trials of bevacizumab for NF2-associated schwannoma have also been conducted in Japan.

  Purpose : Embolization for intracranial tumors currently plays a supporting role to open surgery. The reasons for embolization include : 1) tumor necrosis resulting in a safer operation and more aggressive surgery, 2) reduction in intraoperative bleeding and avoidance of blood transfusion, and 3) decrease in operative time. Functional vascular anatomy and endovascular technique are the most important issues for safe embolization. Herein we report our standard techniques for tumor embolization and compare our results with those of the Japanese Registry of NeuroEndovascular Therapy (JR-NET).

  Methods : Our standard procedure is as follows : 1) embolization is performed several days before open surgery, 2) in cases with strong peritumoral edema, steroid administration or embolization may be performed immediately before surgery, 3) patients undergo the procedure under local anesthesia, 4) insertion of the microcatheter is as close as possible to the tumor, 5) particulate emboli are the first line material, 6) embolization is occasionally performed with N-butyl cyanoacrylate (NBCA) glue, and 7) if possible, additional proximal feeder occlusion with coils is performed.

  Results : During the past 12 years, 169 intra-cranial tumor embolization procedures were performed in our department. Meningioma was the main target of embolization (154 of 169 patients, 91.1%). Seven procedure-related complications were observed, with one permanent complication (0.6%) of hearing loss after anterior inferior cerebellar artery embolization for hemangioblastoma with NBCA. Transient complications included three middle meningeal arterio-venous fistulas, two cranial nerve paresis, and a pseudoaneurysm of the femoral artery (puncture site). We conducted the JR-NET 2 (2007-2009) and JR-NET 3 (2010-2014) in Japan. Complications of tumor embolization occurred in 57 of 1,544 JR-NET 3 patients (3.69%), although the complication rate for JR-NET 2 was only 1.48% (15 of 1,012 patients). Tumors other than meningioma were a significant risk factor for the occurrence of JR-NET 2 complications. Further, embolization of vessels other than the external carotid artery (ECA) and use of liquid embolic material were significantly associated with the development of JR-NET 3 complications. We suggest that more aggressive embolization targeted to vessels other than the ECA and increased application of liquid embolic materials might worsen the risk of complications.

  Conclusions : Although embolization was safe for extra-axial tumors such as meningiomas fed by the ECA, embolization of vessels other than the ECA as occurs in hemangioblastomas was a significant risk factor for complications. Use of liquid embolic material increased the risk for complications. Endovascular neurosurgeons should fully discuss the indications and strategies for preoperative embolization with tumor neurosurgeons to perform safe and effective procedures.

  Skull base meningioma is characterized as a deep-seated compression of the cranial nerves and vessels, with brainstem edema in some cases. Appropriate techniques such as surgical resection, stereotactic radiosurgery/radiotherapy (SRS/SRT), or multimodality treatment combined with resection and radiation should be considered for skull base meningioma. Total resection is the gold standard treatment; however, precise SRS/SRT treatment is appropriate for aged patients when surgical resection of the tumor is contraindicated. Subtotal resection followed by SRS/SRT is also an useful strategy. Boron neutron capture therapy and particle therapy are new treatments that may become available in the near future.

  Craniopharyngiomas have been described as the most challenging intracranial tumors because they originate from the remnants of the Rathke's pouch and extend in various directions from the sella turcia, even reaching the third ventricle. Moreover, there are important anatomical structures such as the hypothalamus, third ventricle, optic apparatus, carotid arteries, and surrounding perforator vessels surround the tumor. The optimal treatment for craniopharyngiomas has not yet been established. However, a complete resection during the first surgical attempt is described as the most effective treatment from an oncological perspective, as treatment of a recurrent lesion may be more complicated. The surgical priority is to maximize resection while preserving the patient's long-term functional outcome and quality of life. A balance between tumor removal and damage to nearby critical neurovascular structures should be found. Radiotherapy is also a good treatment option for recurrent or residual tumors. However, obtaining complete tumor control with radiation therapy is not straightforward, and radiation has been reported to cause injury to the surrounding organs. Currently, several advanced techniques such as an extended transsphenoidal approach, 3D conformal radiotherapy, or monoclonal immunotherapy may be performed. The aim of this report was to summarize the main principles of craniopharyngiomas treatment strategies through a review of the existing literature.

  This retrospective imaging study included 22,470 examinations of 12,265 persons who underwent brain magnetic resonance imaging (MRI) over 11 years during health check-ups at the health check-up center in Chunichi Hospital. All T1-, T2-, fluid attenuation inversion recovery-, and T2^＊-weighted images were recorded and analyzed at every MRI examination. Of the 12,265 subjects (7,954 men and 4,311 women), 66 (0.54% ; 53 men and 13 women) had incidental cerebral cavernous malformations (CCMs). The frequency of CCMs in men (0.67%) was approximately twice as high as that in women (0.3%). The observed frequencies for men and women reported recently in population-based CCM prevalence studies from other countries were similar ; therefore, this study might indicate a more frequent tendency for CCMs in Japanese men.

  Thirty-four subjects harboring CCMs were followed by serial MRI examinations during the study period. Nine CCMs increased in size in this period, and 6 of them exhibited signal characteristics of hyperintensity on T1-weighted MR images.

  Multinodular and vacuolating neuronal tumors (MVNT) were recently included in the 2016 World Health Organization classification of central nervous system tumors. In previous case reports and published papers, MVNTs are described as benign tumors associated with epilepsy and rarely presenting with progressive features. Herein, we report three cases of resected MVNTs with slow progression. None of the patients exhibited neurological symptoms or had a history of epilepsy, and all were diagnosed incidentally using magnetic resonance imaging (MRI). In all three cases, MRI of the subcortical region revealed hypointensity on T1-weighted images (T1-WI) and hyperintensity on T2-WI and fluid-attenuated inversion recovery (FLAIR) images. The T1-WI lesions were not enhanced with gadolinium. One patient demonstrated suggested slow expansion of the lesion during the 7-year follow-up visit. As the results suggested the possibility of progressive tumors, including lower-grade gliomas, surgery was performed to obtain pathological and genetic diagnoses. Histopathological findings revealed typical features of MVNT such as multinodular lesions in the cerebral subcortex and proliferating atypical cells with vacuolating features in the tumors.

  Immunohistochemical tests demonstrated that anti-synaptophysin and anti-Olig2 antibodies stained the tumor cells. DNA sequencing analysis revealed that IDH1-R132, IDH2-R172, H3F3A-K27, -G34, HIST1H3B-K27, -G34, TERT promoter-C228, -C250, and BRAF-V600 were not mutated. Additional data on characteristic features of MVNT revealed by MRI are required to determine treatment strategies for hyperintensity lesions detected on T2-WI, including lower grade gliomas.