Yosuke Yamada

Melanocytic medulloblastoma with ganglioneurocytomatous differentiation : A case report

Melanotic or melanocytic medulloblastoma is a rare variant of medulloblastoma, especially when the tumor shows advanced neuronal differentiation. We report a case of this tumor, which developed in the cerebellar vermis in an 8‐year‐old girl. Initial biopsy specimens were identified as classical medulloblastoma with a high MIB1 index. Surgical removal of the tumor was performed after chemo‐radiotherapy, and black pigments were noticed on the tumor surface. Histologically, the tumor was composed of classical medulloblastoma with the presence of pigmented epithelial cells forming tubules and clusters. Immunohistochemically, the pigmented tumor cells were positive for S100 protein, HMB45, and MART1, indicating that the pigments were derived from melanosomes, and these features were compatible with melanocytic medulloblastoma. Interestingly, some of the non‐pigmented or amelanotic tumor cells were also positive for HMB45 and S100 protein. Although the tumor showed an unusual cell combination, it was distinguished from atypical teratoid/rhabdoid tumor (AT/RT) by nuclear expression of INI1/BAF45 protein. The tumor also possessed ganglion‐like cells within the neuropil matrix, which resembled small mature ganglion cells, and was consequently designated as ganglioneurocytoma. The melanotic medulloblastoma and part of the ganglioneurocytomatous area were fused with each other. Hence, the present case provides new information indicating that melanocytic medulloblastoma differs from AT/RT, and that it can exhibit advanced neuronal differentiation. In addition, reduction of the tumor MIB1 index was observed after chemo‐radiotherapy.

Expression of proteasome subunit β5t in thymic epithelial tumors.

Recently, a proteasome &bgr; subunit expressed exclusively in thymic cortical epithelial cells was discovered in mice and humans. This subunit, designated &bgr;5t, is a component of the thymoproteasome, a specialized type of proteasome implicated in thymic positive selection. To investigate whether &bgr;5t could serve as a marker for the differential diagnosis of thymic epithelial tumors, we performed immunohistochemical analysis using anti-&bgr;5t antibody in 54 cases of thymic epithelial tumors comprising 41 cases of thymomas and 13 cases of thymic carcinomas. &bgr;5t was detected in the neoplastic epithelial cells of thymomas. Among the subtypes of thymoma, expression of &bgr;5t was observed in most cases of type B thymoma (20 of 21) but not in type A thymomas (0 of 3). In type AB thymomas, &bgr;5t expression was variable (6 of 17). Type B3 thymomas (4 cases) were positive for &bgr;5t but negative for CD5, c-kit, and glucose transporter 1 (GLUT-1), which are known as diagnostic markers for thymic carcinomas. In contrast, thymic carcinomas were negative for &bgr;5t (0 of 13) but expressed at least one and usually all of CD5, c-kit, and GLUT-1. Thus, &bgr;5t and CD5/c-kit/GLUT-1 were differentially expressed in type B3 thymoma and thymic carcinoma. We tested &bgr;5t expression in 39 cases of tumors arising from other organs, which showed the specific expression of &bgr;5t in thymic epithelial tumors. This study demonstrates that &bgr;5t is expressed in most type B and in some type AB thymomas and is a marker useful in differentiating type B3 thymomas from thymic carcinomas when used in combination with other diagnostic markers.

Chromophobe renal cell carcinoma, oncocytic variant: a proposal of a new variant giving a critical diagnostic pitfall in diagnosing renal oncocytic tumors

In chromophobe renal cell carcinoma (RCC), two forms of typical and eosinophilic variants have been reported to date. We have previously reported a new variant of chromophobe RCC, namely an oncocytic variant. However, little is known on the histological features of this variant. In this article, we report such five cases. Macroscopically, the tumor was well demarcated, but unencapsulated. The cut surface of the tumor showed brown in color, but neither hemorrhage nor necrosis was seen. Microscopically, the tumor consisted of predominant tubular configuration with or without various proportion of solid-sheet pattern. In one tumor, tumor cells microscopically invaded branches of renal vein. In addition, the constituting cells were characterized by the oncocytic cytoplasm, trivial to minimal variation in tumor size, indistinct to slightly distinct cell border, centrally located round nuclei and the absence of perinuclear halo. These characteristics entirely resembled renal oncocytoma. However, neoplastic cells immunohistochemically showed the diffuse and strong labeling for cytokeratin 7 and mitochondrial antigen in all cases. In addition, in fluorescence in situ hybridization (FISH) study the loss of more than four chromosomes among chromosomes 7, 10, 13, 17 and 21 was confirmed in all tumors and the diagnosis of chromophobe RCC was rendered. In conclusion, we propose a new variant, namely an oncocytic variant, of chromophobe RCC morphologically resembling renal oncocytoma and biologically showing characteristics of chromophobe RCC, and this recognition is practically crucial in the differential diagnosis from renal oncocytoma.

Decreased proteasomal function accelerates cigarette smoke-induced pulmonary emphysema in mice

Chronic obstructive pulmonary disease (COPD) is a disease common in elderly people, characterized by progressive destruction of lung parenchyma and chronic inflammation of the airways. The pathogenesis of COPD remains unclear, but recent studies suggest that oxidative stress-induced apoptosis in alveolar cells contributes to emphysematous lung destruction. The proteasome is a multicatalytic enzyme complex that plays a critical role in proteostasis by rapidly destroying misfolded and modified proteins generated by oxidative and other stresses. Proteasome activity decreases with aging in many organs including lungs, and an age-related decline in proteasomal function has been implicated in various age-related pathologies. However, the role of the proteasome system in the pathogenesis of COPD has not been investigated. Recently, we have established a transgenic (Tg) mouse model with decreased proteasomal chymotrypsin-like activity, showing age-related phenotypes. Using this model, we demonstrate here that decreased proteasomal function accelerates cigarette smoke (CS)-induced pulmonary emphysema. CS-exposed Tg mice showed remarkable airspace enlargement and increased foci of inflammation compared with wild-type controls. Importantly, apoptotic cells were found in the alveolar walls of the affected lungs. Impaired proteasomal activity also enhanced apoptosis in cigarette smoke extract (CSE)-exposed fibroblastic cells derived from mice and humans in vitro. Notably, aggresome formation and prominent nuclear translocation of apoptosis-inducing factor were observed in CSE-exposed fibroblastic cells isolated from Tg mice. Collective evidence suggests that CS exposure and impaired proteasomal activity coordinately enhance apoptotic cell death in the alveolar walls that may be involved in the development and progression of emphysema in susceptible individuals such as the elderly.

Hand-assisted laparoscopic splenectomy for sclerosing angiomatoid nodular transformation of the spleen complicated by chronic disseminated intravascular coagulation: A case report

A 36‐year‐old man who presented with a nosebleed and anemia was referred to our hospital. Laboratory test results showed platelet depletion, decreased levels of fibrinogen, and increased fibrinogen degeneration products. CT showed a 13‐cm splenic tumor. T2‐weighted MRI revealed a high‐intensity mass. We preoperatively diagnosed splenic hemangioma with chronic disseminated intravascular coagulation and scheduled an operation to relieve the disseminated intravascular coagulation. We also performed hand‐assisted laparoscopic splenectomy to ensure easy handling of the splenomegaly. The resected specimen microscopically consisted of hemorrhages and hemangiomatous lesions, and multiple angiomatoid nodules were scattered and separated by fibrocollagenous stroma with inflammatory cells. Three types of vessels (capillaries, sinusoids and small veins) were contained in the angiomatoid nodules, and the pathological diagnosis was sclerosing angiomatoid nodular transformation. The results of this case suggest that we should consider sclerosing angiomatoid nodular transformation in the differential diagnosis of patients with splenic tumors, as sclerosing angiomatoid nodular transformation with hemangiomatous features may cause coagulation disorders for which splenectomy should be performed.

Osteonecrosis and Panniculitis as Life-Threatening Signs

Title Osteonecrosis and panniculitis as life-threatening signs Author(s) Kuwatani, Masaki; Kawakami, Hiroshi; Yamada, Yosuke Citation Clinical Gastroenterology and Hepatology, 8(5): e52-e53 Issue Date 2010-05 Doc URL http://hdl.handle.net/2115/61448 Rights ©2010. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Rights(URL) http://creativecommons.org/licenses/by-nc-nd/4.0/ Type article (author version) File Information PPP_syndrome-CGH-revision2.pdf

Expression of thymoproteasome subunit β5t in type AB thymoma

Type AB thymoma is a thymic epithelial tumour composed of lymphocyte-poor type A and lymphocyte-rich type B components. Although it is categorised as a single entity in the classification of WHO, it shows a broad range of morphology. To investigate whether the functional characteristic of neoplastic cells in type AB thymoma relates to morphological diversity, we performed immunohistochemical analysis using anti-β5t antibody in 20 cases of type AB thymoma. β5t is a recently discovered proteasomal β subunit expressed exclusively in cortical thymic epithelial cells and tumour epithelial cells of thymomas with cortical differentiation. Consistent with our previous observation, β5t was predominantly expressed in the type B component. When the type B component was divided into three groups morphologically, β5t was expressed more frequently in cases with round to polygonal than spindle to oval tumour cells. Furthermore, the ratio of terminal deoxynucleotidyl transferase (TdT)-positive lymphocytes was increased in components with higher expression of β5t. These results indicate that the histological diversity of type AB thymoma correlates with expression of a functional marker β5t and abundance of TdT-positive lymphocytes.

Proteasome subunit β5t expression in cervical ectopic thymoma

Cervical ectopic thymoma is extremely rare, and, till date, <30 cases have been reported in the literature.1 Although typical cases of thymic neoplasms show distinctive morphology, they may pose diagnostic challenges when the specimen consists of only small tissue as often encountered in needle biopsy. Cervical ectopic thymoma is often misdiagnosed as thyroid or lymph node masses; specifically, predominantly lymphocytic thymoma can be misdiagnosed as Hashimotos thyroiditis or malignant lymphoma and predominantly epithelial thymoma as carcinoma, particularly of thyroid origin.2 Therefore, the availability of thymus-specific immunohistochemical markers that can verify thymic epithelial origin would be of great help in getting a proper diagnosis. β5t is a recently discovered proteasomal β subunit expressed exclusively in thymic cortical epithelial cells in both humans and mice.3 ,4 It is a component of specialized 20S proteasomes known …

Arteritic anterior ischemic optic neuropathy with positive myeloperoxidase antineutrophil cytoplasmic antibody

BackgroundMyeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) is related to smallvessel vasculitis. There have been some reports of optic nerve involvements with increased values of MPO-ANCA. We report two cases of anterior ischemic optic neuropathy (AION) in which ANCA-associated vasculitis was suspected to be responsible for the pathogenesis.CasesA 66-year-old man and a 72-year-old man had ocular symptoms of AION in both eyes with positive MPO-ANCA.ObservationsBoth patients showed high erythrocyte sedimentation rate, C-reactive protein, and MPOANCA values at first. Temporal artery biopsies were negative for temporal arteritis, whereas small-vessel vasculitis was found only in the latter patient. Visual dysfunctions remained unchanged after steroid pulse therapy, although laboratory data returned to normal levels after the treatment. Fluorescein angiography revealed selective occlusion of capillaries, arterioles, and precapillaries in the retina and choroid as well as in the optic disc.ConclusionsThe identical characteristics of the angiographic findings of both eyes in the two cases indicated that the obliteration of small vessels in the intraocular arterial system was closely related to MPO-ANCA-associated vasculitis.