A Cerebral Embolism Caused by a Malignant Peripheral Nerve Sheath Tumor in a Patient with Neurofibromatosis Type 1.

A 31-year-old man with neurofibromatosis type 1 (NF-1) had undergone resection of a malignant peripheral nerve sheath tumor (MPNST) on the buttock 3 months previously. He subsequently underwent mechanical thrombectomy for a hyperacute left middle cerebral artery embolism. Histopathologically, the emboli comprised neurofilament-positive pleomorphic tumor cells with geographic necrosis and conspicuous mitosis and were identified as MPNST. The patient died of respiratory failure due to lung MPNST metastasis on day 15 of hospitalization. To our knowledge, this is the first report of a spontaneous cerebral embolism due to MPNST in a NF-1 patient.

High-grade Solid Pseudopapillary Neoplasms of the Pancreas: Distinct Clinicopathological Malignant Features With Intriguing Gene Alterations through a Comparison With the Conventional Type.

Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for ß-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P <0.001); true necrosis (100% vs. 0%, P <0.001); high-grade nuclear atypia (100% vs. 0%, P <0.001); lymphatic and/or venous invasion (100% vs. 20%, P =0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P <0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P <0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1 mutations. Two HG-SPN cases showed RB1 mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53 mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.

The Diagnostic Utility of RAS Q61R Mutation-specific Immunohistochemistry in Epithelial-Myoepithelial Carcinoma.

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland cancer characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells. Because of its histologic variety and overlap of histologic features with other salivary gland tumors, there are broad differential diagnoses. The HRAS Q61R mutation has been reported to be frequent in and specific to EMC. We evaluated the usefulness of RAS Q61R mutant-specific immunohistochemical (IHC) staining for detecting this genetic alteration in EMC. We investigated 83 EMC cases and 66 cases of salivary gland tumors with an EMC-like component, including pleomorphic adenoma, adenoid cystic carcinoma, basal cell adenoma/adenocarcinoma, and myoepithelial carcinoma. Sanger sequencing was performed for HRAS, KRAS, and NRAS. The diffuse and membranous/cytoplasmic RAS Q61R IHC expression was observed in 65% of EMC cases, in which all cases harbored the HRAS Q61R mutation. IHC-positive cases were present only in de novo EMCs (54/76 cases, 71%) but not in EMCs ex pleomorphic adenoma. The immunoreactivity was almost always restricted to the myoepithelial cells. Conversely, all EMC cases lacking the HRAS Q61R mutation were negative on IHC. In addition, only 3% of EMC-like tumors showed the abovementioned immunopositivity. None of the cases examined carried KRAS or NRAS mutations. IHC for RAS Q61R is highly sensitive and specific for detecting the HRAS Q61R mutation in EMC. Since significant immunopositivity was almost exclusively identified in nearly two thirds of EMCs but seldom in the histologic mimics, the IHC of RAS Q61R is a useful tool for diagnosing EMC in general pathology laboratories.

First experimental verification of the neutron field of Nagoya University Accelerator-driven neutron source for boron neutron capture therapy.

As the commissioning phase of the Nagoya University Accelerator-driven Neutron Source for boron neutron capture therapy, in-phantom thermal neutron flux measurements were conducted using a small 6LiF/Eu:CaF2 scintillator detector and activation foils. The spatial distribution of the measured thermal neutron flux agreed with the Monte Carlo simulation results. Based on this comparison, the free-in-air neutron spectrum, calculated at the exit aperture, was verified and the epithermal neutron flux, at a 0.25 mA proton current, was evaluated as (1.49 ± 0.10) × 107 n/(cm2 s).

Quantitative assessments of arousal by analyzing microsaccade rates and pupil fluctuations prior to slow eye movements.

It is well known that a decline of arousal level causes of poor performance of movements or judgments. Our previous study indicates that microsaccade (MS) rates and pupil fluctuations change before slow eye movements (SEMs) (Honda et al. 2013). However, SEM detection of this study was obscure and insufficient. In this study, we propose a new SEM detection method and analyze MS rates and pupil fluctuations while subjects maintain their gaze on a target. We modified Shin et al.'s method, which is optimized for EOG (electrooculography) signals, to extract the period of sustaining SEMs using a general eye tracker. After SEM detection, we analyzed MS rates and pupil fluctuations prior to the initiation of SEMs. As a result, we were able to detect SEMs more precisely than in our previous study. Moreover, the results of eye movements and pupil fluctuations analyses show that gradual rise of MS rate and longitudinal miosis are observed prior to the initiation of SEMs, which is consistent with our previous study. These findings suggest that monitoring eye movements and pupil fluctuations may evaluate the arousal level more precisely. Further, we found that these tendencies become more significant when they are restricted to the initial SEMs.

Quantitative evaluation of arousal level based on the analyses of microsaccade rates and pupil fluctuations.

In this study, we proposed an objective estimation of decline of arousal level by analyzing microsaccade rate and pupil fluctuation while subjects were continuously gazing a fixation target. Previous studies show that the slow eye movements (SEMs) could be a candidate for an indicator of decline of arousal. However, it is not sufficient to evaluate transition of arousal states since SEMs appear just prior to sleep onset. To establish more objective assessment of arousal, we examined the effects of the transition of arousal on microsaccade rate and pupil fluctuation. The subjects were instructed to indicate by mouse clicks when they were aware of having slept. We have analyzed the eye movement and pupil fluctuation data in advance of the occurrence of SEMs which were detected just before the mouse clicks. In the results, longitudinal pupil diameter shrinking and gradual rise of microsaccade rate were observed prior to SEMs. These results suggest that the arousal level could be evaluated by monitoring eye movements and pupil fluctuations.