Psychiatric symptoms of schizophrenia suggest alteration of cerebral neurons. However, the physical basis of the schizophrenia symptoms has not been delineated at the cellular level. Here, we report nanometer-scale three-dimensional analysis of brain tissues of schizophrenia and control cases. Structures of cerebral tissues of the anterior cingulate cortex were visualized with synchrotron radiation nanotomography. Tissue constituents visualized in the three-dimensional images were traced to build Cartesian coordinate models of tissue constituents, such as neurons and blood vessels. The obtained Cartesian coordinates were used for calculating curvature and torsion of neurites in order to analyze their geometry. Results of the geometric analyses indicated that the curvature of neurites is significantly different between schizophrenia and control cases. The mean curvature of distal neurites of the schizophrenia cases was ~1.5 times higher than that of the controls. The schizophrenia case with the highest neurite curvature carried a frame shift mutation in the GLO1 gene, suggesting that oxidative stress due to the GLO1 mutation caused the structural alteration of the neurites. The differences in the neurite curvature result in differences in the spatial trajectory and hence alter neuronal circuits. It has been shown that the anterior cingulate cortex analyzed in this study has emotional and cognitive functions. We suggest that the structural alteration of neurons in the schizophrenia cases should reflect psychiatric symptoms of schizophrenia.

Spatial resolution is a fundamental parameter in structural sciences. In crystallography, the resolution is determined from the detection limit of high-angle diffraction in reciprocal space. In electron microscopy, correlation in the Fourier domain is used for estimating the resolution. In this paper, we report a method for estimating the spatial resolution of real images from a logarithmic intensity plot in the Fourier domain. The logarithmic intensity plots of test images indicated that the full width at half maximum of a Gaussian point spread function can be estimated from the images. The spatial resolution of imaging X-ray microtomography using Fresnel zone-plate optics was also estimated with this method. A cross section of a test object visualized with the imaging microtomography indicated that square-wave patterns up to 120-nm pitch were resolved. The logarithmic intensity plot was calculated from a tomographic cross section of brain tissue. The full width at half maximum of the point spread function estimated from the plot coincided with the resolution determined from the test object. These results indicated that the logarithmic intensity plot in the Fourier domain provides an alternative measure of the spatial resolution without explicitly defining a noise criterion.

We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients.

We described the first case of IgG4-related hypophysitis without pituitary insufficiency. However, further case collection is needed to characterize the pathophysiology of IgG4-related hypophysitis.

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.

To the Editor, Mucoepidermoid carcinoma (MC) of the salivary glands is a malignant epithelial tumor that is composed of varying proportions of mucus, epidermoid, intermediate, columnar, and clear cells [2]. It is classified into low-, intermediate-, and high-grade types on the basis of morphologic and cytologic features [2, 6]. Although mucous, intermediate, and epidermoid cells are predominant in most MCs, it is well known that clear cells very infrequently predominate over other cell types [1, 2, 3, 4, 5]. Such cases are called clear cell variant of MC [1, 2, 3, 4, 5]. The authors here report a rare case of MC of the palate composed exclusively of clear cells.A 42-year-old Japanese man presented a palate mass measuring approximately 2 cm in diameter. The mass in the palate was whitish pink and relatively hard in consistency. The overlying mucosa showed mild hyperemia. A needle biopsy was performed, and it showed clear cells that were arranged in a medullary, solid pattern (Fig. 1). The clear cells had small hyperchromatic nuclei and abundant clear cytoplasm. A low-grade malignant tumor was suspected pathologically, and the tumor was excised with wide margins. Scrutiny of visceral organs including kidneys showed no remarkable changes. The patient is now free of disease 11 months after the operation.Grossly, the resected tumor measured 202012 mm and was whitish tan in color and relatively hard in consistency. The mucosal surface showed mild erosion. Histologically, the tumor was composed exclusively of clear tumor cells (Fig. 2A). They were arranged in a medullary, sheet-like, and solid pattern separated by thin fibrous septae (Fig. 2B). Invasions into the surrounding mucosa and minor salivary glands were recognized. Clusters of non-clear cells having small hyperchromatic nuclei and small acidophilic cytoplasm were noted in a very few areas (Fig. 2C). They were regarded as intermediate cells. These cells appeared to merge with the clear cells (Fig. 2C). Relatively large cells with mucus in the cytoplasm were scattered in a very small number (Fig. 2D). These cells were considered as mucous cells. The proportions of clear cells, intermediate cells, and mucous cells were approximately 95%, 4%, and less than 1%, respectively. The surgical margins were negative for tumor cells. Cytologically, the clear cells showed small hyperchromatic nuclei that were centrally located in the cytoplasm (Fig. 2B). The cytoplasm was clear, and cell membranes were clearly recognized. Neither keratinization nor intercellular bridges were recognized. The intermediate cells showed small hyperchromatic nuclei and small acidophilic cytoplasm (Fig. 2C). The mucous cells show acidophilic mucin-like materials in the cytoplasm T. Terada ( ) ) · S. Ikeuchi

Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7–9 μm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich-hepatocellular carcinoma (HCC) was challenging. The patient was a 50-year-old woman in whom a 3-cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well-demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid-rich type HCC because it stained positive for Hep Par1, but negative for arginase-1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF-1 and 3β-HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase-1 is to rule out the possibility of lipid-rich HCC.