bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory Pseudotumor of the Spleen:Report of a Case with an Immunohistochemical Study
Authors: Iwafuchi Mitsuya , Watanabe Hidenobu , Maejima Takehito , Okamura Naotaka , Miwa Kouji
Published: August 2010

A 81‐year‐ old Japanese man with a splenic inflammatory pseudotumor is described. The pseudotumor was un changed in size after one year of observation. Macro‐scopically, the lesion was a firm well‐circumscribed 5.5X 5×5cm mass showing a yellowish‐white cut surface. Histologically, it was composed of abundant mixed inflammatory infiltrates, predominantly UCHL‐1(+) T and L26(+) B lymphocytes, plasma cells containing various immunoglobulin subtypes, and S 100 protein(+), and lysozyme and NCA(+) histiocytes, with a sclerotic stroma. Small numbers of eosinophils, neutrophils and foamy macrophages were admixed. The patient has remained disease‐free for 14 months after splenectomy. Only ten splenic inflammatory pseudotumors have been reported in the literature. This paper adds an additional case, together with details of immunohistochemical polyclonality of each inflammatory cell population, confirming that this disease is a nonspecific inflammatory change. Acta Pathol Jpn 42:376–381, 1992.
Immunoreactive Copper‐Zinc Superoxide Dismutase in Damaged Human Myocardium
Authors: Sato Ryugo , Kashima Kenji , Yokoyama Shigeo , Nakayama Iwao
Published: August 2010

The myocardium in 50 autopsy cases was studied using immunostaining for copper zinc superoxide dismutase (CuZn SOD) and standard histochemical procedures. Mucinous degeneration observed in 42 cases showed moderately enhanced expression of immunoreactive CuZn SOD in lesions which were stained strongly by periodic acid‐Schiff but negative with Heidenhain iron‐hematoxylin (HIH), von Kossa and luxol fast blue (LFB) stains, whereas coagulation necrosis in 4 cases revealed almost identical immunostaining for CuZn SOD and HIH to that of contraction band necrosis, i.e. strongly positive HIH staining but negative immunostaining. Basophilic alteration of the myocardial cells in sections fixed with 4% formalin in 2% calcium acetate was seen in 29 cases, being identified frequently in isolated cells as well as in several foci varying considerably in size. This type of alteration demonstrated significantly enhanced expression of immunoreactive CuZn SOD and was strongly positive with von Kossa and LFB stains. The present study indicates that the myocardium can be affected by free radicals produced in any organ of the body, and that subsequently, insoluble phospholipids react with calcium ions in the fixative and accumulate in the basophilic sarcoplasm.
Immunogenic Deposition and Destruction of Glomerulus in IgA Nephritis
Authors: Shigematsu Hidekazu , Kobayashi Yutaka , Tateno Sumio , Hiki Yoshiyuki , Kuwao Sadahito
Published: August 2010

The correlation between glomerular immune deposition and histological alteration was studied in serial paraffin sections of kidney biopsy specimens from patients with IgA nephritis using the peroxidase antiperoxidase (PAP) method. IgA deposition was detected in preserved glomerular extracellular matrix or in newly formed interposed matrix along the capillary loops (mesangial interposition). On the other hand, deposition of IgA was scanty or absent in the distorted extracellular matrix where severe exudative inflammation or extracapillary escape of exudates was occurring segmentally. Ultrastructurally such extracellular matricial destruction was expressed as splitting or thinning of the lamina densa, as well as mesangial edema, reticulation or mesangiolysis of the axial matrix. Therefore it appears that at least two types of change in the extracellular matrix are induced by IgA immune complexes in IgA nephritis; immunogenic deposition and destruction.
Small Cell (Endocrine Cell) Carcinoma of the Gallbladder with Squamous and Adenocarcinomatous Components
Authors: Iida Yumi , Tsutsumi Yutaka
Published: August 2010

Small cell (endocrine cell) carcinoma of the gallbladder in a 62‐year‐old woman is reported. The palliative cholecystectomy specimen revealed a submucosally invading tumor with extensive hemorrhagic necrosis. At autopsy, performed five months after surgery, a huge tumor measuring 14×12×8cm was located at the liver hilus. No signs or symptoms related to overproduction of hormones were recorded throughout her illness. Neither lung lesions nor gall stones were identified. Histologically, diffuse proliferation of small, spindle shaped atypical tumor cells with numerous mitoses was evident. Intraepithelial tumor cell proliferation in the gallbladder mucosa was seen focally. The neuroendocrine nature of the tumor cells was confirmed by the histologic pattern of growth with pseudo‐rosette formation, positive reaction for Grimelius' argyro‐philia, neuron‐specific enolase and Leu 7, and ultra‐structural demonstration of neuroendocrine‐type granules. Immunostaining for a variety of hormones was all negative. Characteristically, foci with squamous and adenocarcinomatous differentiation were identified in the tumor tissue. The glandular components were immuno‐reactive for carcinoembryonic antigen, secretory component, epithelial membrane antigen and CA19–9. The histogenesis and totipotentiality of the neoplasm were discussed.
Multicentric Reticulohistiocytosis
Authors: Kuwabara Hiroko , Uda Hirotsugu , Tanaka Sumiko
Published: August 2010

Electron microscopic examination of multicentric reticulohistiocytosis (MR) cells is reported. Most of the cells contained numerous dense bodies which seemed to be lysosomes. Complex interdigitations of the membranes of the adjacent MR cells were distinctive findings. Some of the cells contained myelinated dense bodies in the cytoplasm. Histochemically, the cells were strongly positive for acid phosphatase, alpha‐naphthyl butyrate esterase and lysozyme. From these observations, the majority of MR cells appeared to be proliferations of monocyte/macrophage derived cells. In the synovium, these cells resembled type A synovial cells. Other smaller and fewer cells had many rough endoplasmic reticulum (RER), and these resembled type B synovial cells. In the synovium, MR cells might be formed by proliferation and fusion of synovial cells.
Nodular Sclerosing Hodgkin's Disease Showing Positive Reaction for Anti‐IL 6/BSF2 Antibody
Authors: Matsumoto Masahiro , Aozasa Katsuyuki , Ohsawa Masahiko , Ikeda Hiroshi
Published: August 2010

A 53 year‐old man presented with bilateral cervical lymph node swelling and low fever. Swollen lymph node was biopsied, and diagnosed as nodular sclerosing Hodgkin's disease (HD). By combined radio‐ and chemotherapy, he went into complete remission. After 3 years, fever of 38 39.2 C and lymph node swelling appeared in the para aortic region and later became systemic. A biopsy was diagnosed as syncytial variant of HD with aid of immunohis‐tochemistry on frozen sections. Large atypical mono‐ or binucleated cells reacted with anti interleukin 6 (IL‐6) antibody. The patient's disease progressed with fever, and he died 66 months after the onset of disease. A previous biochemical study showed that IL‐6 displayed a real relation to the generation of fever. Therefore it is suggested that fever in this patient is related to IL‐6.
An Immunohistochemical and Ultrastructural Study of Case of Small‐cell Neuroendocrine Carcinoma in the Ampullary Region of the Duodenum
Authors: Sarker Ashit Baran , Hoshida Yoshihiko , Akagi Seiji , Hayashi Kazuhiko , Murakami Ichiro , Jeon Hou Jong , Takahashi Kiyoshi , Akagi Tadaatsu
Published: August 2010

One case of small‐cell neuroendocrine carcinoma in the ampullary region of the duodenum is reported. The histological appearance of the tumor was identical to pulmonary small‐cell carcinoma. Neuroendocrine differentiation was demonstrated immunohistochemically by positive immunoreaction for neuron specific enolase, Leu 7 and chromogranin, and ultrastructurally by the presence of scanty dense core neurosecretory type granules. Small‐cell neuroendocrine carcinoma in the ampulla of Vater is extremely rare. To our knowledge, this is the sixth reported case.
Aging and Immunity
Authors: Hirokawa Katsuiku , Utsuyama Masanori , Kasai Michiyuki , Kurashima Chieri
Published: August 2010

The function of the immune system peaks at around puberty and gradually declines thereafter with advance in age. The age‐related decline of immunological function primarily occurs in the T cell‐dependent immune system and is generally associated with increase in susceptibility to infections as well as in incidence of autoimmune phenomena in the elderly. The age‐related change in T cell‐dependent immune functions can be ascribed to the physiological thymic atrophy which starts in an early stage of life. Emigration of T cells from the thymus to the periphery mainly takes place in the late fetal and newborn stage, and dramatically declines after puberty. In other words, the thymic capacity to promote T cell differentiation starts to change in the early stage of life in terms of quantity and quality of T cells. Thus, the composition of T cell‐subsets in the periphery gradually changes with age, resulting in the alteration of T cell functions in the elderly. The restoration of immunological functions of the aged individuals is possible and might be beneficial for them to cope with various diseases associated with aging. Physiological thymic atrophy is controlled by both extrathymic and intrathymic factors, and is not a totally irreversible process. The process of thymic atrophy might be explained by further understanding of the relationship between the neuroendocrine and the immune systems. Acta Pathol Jpn 42: 537–548, 1992.
Multiple penetrating colonic ulcers in secondary amyloidosis caused by rheumatoid arthritis
Authors: Ishikawa Yukio , Ishii Toshiharu , Masuda Shigeru , Asuwa Noriko , Kiguchi Hideko
Published: August 2010

An autopsy case of multiple penetrated colonic ulcers with secondary amyloidosis caused by rheumatoid arthritis in a 61 year old woman is reported. Amyloid deposition was conspicuous in the transverse colon with numerous penetrating ulcers that were circumferentially scattered. Deposition was mainly in the small vessel walls of the submucosal layers. In the quantitative comparison of the histological components between the colonic segments affected by severe and mild ulcer formation, occlusive vascular amyloid deposition was revealed more frequently in the severe involved portion than in the mild involved portion. In addition, submucosal fibrosis that tended to appear around ulcers was more extensive and thicker in the former than in the latter. The complete vascular occlusion caused by amyloid deposition was particularly concentrated in the submucosal layer adjacent to the ulcer. These findings indicate that peripheral circulatory disturbance by amyloid deposition in the small vascular walls leads to ulcer formation in the colon.
Primary leiomyosarcoma of the thyroid gland
Authors: Lida Yoji , Katoh Ryohei , Yoshioka Masakazu , Oyarna Toshio , Kawaoi Akira
Published: August 2010

A primary leiomyosarcoma of the thyroid gland in a 72 year old Japanese woman is described. This is the second case reported in the English literature. The patient presented with a 7 month history of a gradually expanding tumor in the right neck. The surgical specimen taken by thyroid lobectomy revealed a relatively well demarcated tumor, 2X2X3 cm in size, confined to the right lobe. Histologically, the tumor showed a classical leiomyosarcomatous appearance of interlacing fascicles of spindle‐shaped cells with occasional blunt‐ended nuclei and a high frequency of mitotic figures. lmmunohistochemistry of the tumor cells clearly showed smooth muscle differentiation; the cells were positive for desmin, muscle‐specific action and vimentin and negative for cytokeratin, epithelial membrane antigen, carcinoembrionic antigen, thyroglobulin and calcitonin. The patient was free of disease for 3 years and 11 months without further treatment when evidence of multiple bone metastases appeared on bone scintigraphy. She died of pneumonia 4 years and 3 months after the lobectomy.
Heat‐induced antigen retrieval of proliferating cell nuclear antigen and p53 protein in formalin‐fixed, paraffin‐embedded sections
Authors: Kawai Kenji , Serizawa Akihiko , Hamana Toshiyasu , Tsutsumi Yutaka
Published: August 2010

Immunohistochemical demonstration of proliferating cell nuclear antigen (PCNA) and p53 protein is important, particularly for the surgical diagnosis of neoplastic disorders. An effective, simple and reproducible method was established for observing the expression of these intranuclear antigens in routinely processed, formalin‐fixed paraffin‐embedded sections. Dramatic improvement of the antigenicity was obtained when the deparaffinized sections were heated in a hot water bath at 90°C for 120 rnin in 0.01 mol/L citrate buffer, pH 6.0, for PCNA and in 0.01 mol/L phosphate‐buffered saline, pH 7.2, for p53 protein. These reliable pre‐treatments are useful for the detailed comparative analysis of the expression of PCNA and p53 protein and fine histologic architecture and for retrospective study using a large number of archival specimens.
Sinusoidal capillarization in small hepatocellular carcinoma
Authors: Kin Motoaki , Torimura Takuji , Ueno Takato , Inuzuka Sadataka , Tanikawa Kyuichi
Published: August 2010

The morphological and phenotypic changes of sinusoidal endothelial cells in hepatocellular carcinoma were investigated along with the hemodynamic changes. Hepatocellular carcinomas, which were 10–20 mm in diameter, were obtained by liver aspiration biopsy. Twenty specimens of well differentiated and 20 specimens of moderately differentiated hepatocellular carcinoma were used. These were classified into two groups of hepatocellular carcinoma: with and without hypervascularity. Electron microscopy, immunohistochemistry using antibodies against factor VIII‐related antigen, type IV collagen and laminin and lectin histochemistry using Ulex europaeus agglutinin I (UEA‐I) were performed. Factor VIII‐related antigen and UEA‐1 binding sites were present in the sinusoidal endothelial cells in two groups. In hepatocelMar carcinoma with hypervascularity, type IV collagen and laminin were present corresponding to basement membranes along the endothelial cells, which had few fenestrae. In another group, although type IV collagen was present along the endothelial cells that had a few fenestrae, laminin and basement membranes were rarely observed. These results suggest that the sinusoidal endothelial cells tend to show phenotypic changes in the early stage of hepatocarcinogenesis. As the arterial blood supply for hepatocellular carcinoma increases, the sinusoidal endothelial cells may form basement membranes and take on the morphological appearance of capillaries.
Effect of traditional Chinese medicine (Sairei‐to) on monoclonal antibody‐induced proteinuria in rats
Authors: Kawachi Hiroshi , Takashima Noriko , Orikasa Michiaki , Oite Takashi , Shimizu Fujio
Published: August 2010

The effects of traditional Chinese medicine (Sairei‐to) on monoclonal antibody (mAb) inducing proteinuria were examined. Four hundred, 200 and 100mglkg body weight (BW) of Sairei‐to and phosphate‐buffered saline (PBS) as a control were injected intraperitoneally into four groups of female Wistar rats every day from 5 days before intravenous injection of mAb to the end of the experimental period. The amount of urinary protein excretion was significantly suppressed in roughly a dose‐dependent manner. For example, 116.6 ± 89.7mg/day of proteinuria was observed in control groups compared to 4.2 ± 15.2 mglday in the 400 mglkg BW of Sairei‐to treated group 2 days after mAb injection (P < 0.01).

Statistically significant (P <0.01) differences were again observed in a repeat experiment (122.1 ± 53.7 vs 10.2 ± 10.1 mglday on the 2nd day) without affecting the glomerular filtration rate.

No significant difference was recognized between the total amount of mAb bound to glomeruli 1 h after mAb injection in Sairei‐to‐treated and non‐treated rats, indicating that Sairei‐to pretreatment has no effects on the number or quality of antigenic molecules.

The effect of Sairei‐to on a non‐immunological model of proteinuria was also examined. No significant reduction of proteinuria by similar Sairei‐to treatment was observed in aminonucleoside of puromycin nephropathy.

The authors conclude that mAb‐induced proteinuria in rats is significantly suppressed by the traditional Chinese medicine, Sairei‐to.
A review of 79 thymomas: Modification of staging system and reappraisal of conventional division into invasive and non‐invasive thymoma
Authors: Koga Kenji , Matsuno Yoshihiro , Noguchi Masayuki , Mukai Kiyoshi , Asamura Hisao , Goya Tomoyuki , Shimosato Yukio
Published: August 2010

A clinicopathological study of surgically resected thymomas was performed using Masaoka's staging and modified Masaoka's staging systems, and the utility of these two staging systems was compared. The modification enabled adjustment for the disproportion in the number of cases between Stage I and Stage II. Analysis of survival rates, according to the tumor stage, indicated that the old classification should be reappraised, that is, division into non‐invasive and invasive thymomas, although staging may contribute to the indication for postoperative radiotherapy, especially for Stage II disease. Analysis of the cases showed a wide spectrum of aggressiveness, varying from cases showing slow progression with a relatively favorable prognosis, such as the spindle cell type, to cases with rapid progression leading to tumor death in a relatively short time, such as the epithelial cell predominant and polygonal cell type. The pathological stage at the time of first surgical resectlon would reflect the degree of aggressiveness of thymoma in many instances. Therefore, not only staging the tumor extent but also grading of its aggressiveness are needed in order to predict the prognosis of patients with thymoma. For the latter, histology and cytopathology are helpful.
Captopril reduces collagen and mast cell and eosinophil accumulation in pig serum‐induced rat liver fibrosis
Authors: Ramos Simone G. , Montenegro André P. , Goissis Gilberto , Rossi Marcos A.
Published: August 2010

The effect of captopril on the development of hepatic septal fibrosis in a specific experimental model produced by repeated injections of whole pig serum into the peritoneal cavity of rats was studied. The results afforded four basic conclusions. First, the experimental model used seems to be a pure form of septal fibrosis, which depends on active tissue fibroplasia, without hepatocyte necrosis. The fibrotic septa, located between limiting plates of adjacent classic hepatic lobules, and delimiting the classic liver lobule, consisted of collagen fibers infiltrated by eosinophils, mast cells, fat‐storing cells (Ito cells), transitional cells and interstitial fibro‐blasts. Second, the angiotensin‐converting enzyme inhibitor captopril attenuated the hepatic fibrosis induced by pig serum administration, as proven by a decrease In hepatic hydroxyproline concentration and histological examination of the liver. Third, this attenuation of hepatic fibrosis might be related, at least in part, to diminished mast cell and eosinophil accumulation in the hepatic tissue. Finally, these data may indicate a novel action of angiotensin‐converting enzyme inhibitor in general, and for captopril in particular, as drugs potentially capable of reducing eosinophils in fibrotic processes.
Quantitative morphology of human cirrhotic livers. Part II: The statistically adequate morphological classification of liver cirrhosis. Multivariate analysis from quantified data of form
Authors: Chiba Ryoji , Takahashi Tohru
Published: August 2010

In a previous report, we developed methods by which to quantify various patterns of cirrhosis. A set of parameters were used: (i) the mean nodular radius; (ii) the coarseness; (iii) the mean septal thickness; and (iv) the degree of nodular separation. This was applied to 70 cirrhotic livers in an attempt to establish a reproducible classification, and the data were subjected to four‐dimensional cluster analysis (Ward method) using a mainframe computer. Five clusters appeared: cluster A, fine nodules, thin septa; cluster B, coarse nodules, relatively thin septa; cluster C, fine nodules, thick septa; cluster D, extremely coarse nodules; and cluster E, coarse nodules, thin septa and incomplete nodulation. Of these, cluster A was considered to correspond to the nutritional type of Gall, cluster B to posthepatitic type (Nagayo's Type B), cluster C to postnecrotic type (Nagayo's Type A) and cluster E to the subtype of posthepatitic cirrhosis with incomplete nodulation (Miyake's Type B'). Cluster D comprised cases with extremely coarsened nodules. The repro‐ducibility of this clustering was fully ensured by linear discriminant analysis. Another discriminant analysis, the canonical, allowed us to visualize the separation of clusters in a two‐dimensional (2‐D) scatter diagram. We thus managed to establish a most adequate classification from a geometric and statistical point of view.
Histologic and immunohistochemical study of clinically non‐functioning pituitary adenomas
Authors: Sano Toshiaki , Yamada Shozo
Published: August 2010

Seventy‐five clinically non‐functioning pituitary adenomas were characterized in terms of their histologic and immunohistochemical features. Fourteen adenomas (18.7%) were positive for hormones other than gonadotropins. These included two somatotroph adenomas, three lactotroph adenomas, four thyrotroph adenomas, four corticotroph adenomas and one unusual plurihormonal adenoma. Fifty‐five adenomas (73.3%) were exclusively positive for one or more gonadotropin subunits (β‐follicle stimulating hormone, p‐luteinizing hormone, and α‐subunit of glycoprotein hormones), but negative for other hormones such as growth hormone and β‐thyrotropin. Histologically, a papillary arrangement along the capillary was most characteristically observed in the gonadotropin‐positive adenomas. Five of six adenomas negative for any pituitary hormones exhibited the typical papillary structure. Thus, approximately 80% of clinically non‐functioning adenomas constituted a single tumor group that shared the common histologic features of gonadotroph adenomas. These findings suggest that nearly all tumor types of clinically non‐functioning adenomas can be diagnosed solely by light microscopy in combination with immunohistochemistry, and that the vast majority of them may be gonadotroph adenomas.
Coexistence of choriocarcinoma and hepatoid adenocarcinoma in the stomach
Authors: Motoyama Teiichi , Aizawa Kikuo , Fujiwara Takato , Endoh Yasushi , Watanabe Hidenobu
Published: August 2010

The case is presented of a 46 year old woman who had a gastric tumor with components of choriocarcinoma, hepatoid adenocarcinoma and common types of adenocarcinoma. Although two histologic types of tumor producing carcinoplacental or carcinofetal proteins were contained within the tumor, immunohistochemical analyses, especially of placental alkaline phosphatase, clearly showed that each component was present separately within the same tumor. It was only hepatoid adenocarcinoma cells that permeated the lymph and blood vessels. After the recurrence, the serum level of alpha‐fetoprotein (AFP) markedly elevated, but that of human chorlonlc gonadotropin β‐subunit (hCG‐β) was always within normal range. These findings Indicate that in the present case the hepatoid adenocarcinoma component was more aggressive in growth than the choriocarcinoma component.
Intraductal carcinoma of the breast arising in sclerosing adenosis
Authors: Ichihara Shu , Aoyama Hideaki
Published: August 2010

An unusual case of intraductal carcinoma of the breast arising in sclerosing adenosis is reported. A 49 year old Japanese woman noticed a lump in her right breast 3 years before she sought medical advice. Histologic examination of the lumpectomy specimen showed, adjacent to intraductal papilloma, sclerosing adenosis involved in a neoplastic cellular proliferation with cribriform pattern and comedo necrosis. lmmunohistochemical study with antl‐actin antibodies discriminated intraductal carcinoma from adjacent sclerosing adenosis by highlighting myoepithelial components in the latter. Extensive sampling revealed no carcinoma outside the sclerosing adenosis, implying that the intraductal carcinoma did originate in the tubules of sclerosing adenosis. A review of the literature indicated that the ductal to lobular ratio among carcinoma in situ concurring with sclerosing adenosis is about 1:2. The average age of patients with ductal and lobular carcinoma in situ in sclerosing adenosis is 39 and 43.7, respectively. It is suggested that carcinoma in situ arising in sclerosing adenosis and fibroadenoma have a similar biological basis.
Progressive activity in latent prostate carcinoma defined by argyrophilic staining of the nucleolar organizer regions (AgNOR)
Authors: Konishi Noboru , Nakaoka Shingo , Tsuzuki Toshihide , Kitahori Yoshiteru , Nishii Kiyoharu , Kitamura Motokazu , Ohshima Masato , Hiasa Yoshio
Published: August 2010

Argyrophilic staining of the nucleolar organizer regions (AgNOR) was studied in 30 cases of benign prostatic hyperplasias (BPH), 17 cases of latent prostate carcinomas, 50 cases of clinical carcinomas and seven cases of metastatic lesions from prostate carcinomas. The criteria for these comparisons were the number of positive‐staining dots per nucleus, the area of the dots, and a relative score determined by multiplying the number of positive‐staining dots in the nuclei by the areas of the dots. Overall, there were no significant differences in these three parameters between BPH and latent carcinomas. Among latent carcinomas, however, significantly higher AgNOR scores were observed for infiltrative lesions than for non‐infiltrative lesions. AgNOR dot number, area and score increased as tumors became less differentiated, with no significant differences detected in metastatic versus non‐metastatic carcinomas. These results suggest that some latent tumors are similar in biological behavior, such as cell proliferation, to clinical carcinoma.
Primary epithelioid malignant schwannoma of the lung
Authors: Kitamura Hitoshi , Kitamura Hajirne
Published: August 2010

This is the first documented report of a case of primary malignant nerve sheath tumor of the lung showing an epithelioid malignant schwannoma. A 55 year old Japanese female underwent lobectomy of the middle lobe of the right lung because of a large, rounded tumorous shadow found on chest X‐ray film. Light microscopic examination of the neoplasm disclosed an epithelioid malignant schwannoma with foci having a spindle‐cell sarcomatous pattern. The neoplastic cells were positive for S‐100 protein and neuron specific enolase by the immunoperoxidase method. Transmission electron microscopy showed basement membrane‐like material surrounding the neoplastic cells and long spacing collagens in the interstitial spaces. The patient died of a recurrent tumor in the right hemithorax 5 months after undergoing lobectomy. An autopsy revealed no primary site of the neoplasm outside the lung. Furthermore, there was no evidence of neurofibromatosis.
Three synchronous carcinomas of the papilla of Vater, common bile duct and pancreas
Authors: Nishihara Kazuyoshi , Tsuneyoshi Masazumi , Shimura Hideo , Yasunami Yohichi
Published: August 2010

Multiple carcinomas of the pancreatico‐biliary tree are rare. A 53 year old Japanese man was diagnosed as having an adenocarcinoma in the papilla of Vater. During the operation, he was also found to have a polypoid mass in the common bile duct. While cutting the operative specimen into stepwise sections, a small tumor was also detected incidentally in the main pancreatic duct of the pancreatic head. Histologically, all three tumors proved to be papillary adenocarcinomas and were restricted to the mucosa. lmmunohistochemically, all three tumors were positive for carcinoembryonic antigen, carbohydrate antigen 19–9, chromogranin A and serotonin, while they were negative for somatostatin. lmmunoreactivity to the tumor suppressor gene p53 protein (PAb 1801) was found in all three tumors. A flow cytometric analysis of the cellular DNA content revealed all three tumors to be aneuploid. The above results suggested that these three tumors from different sites all had the same histological, immunohistochemical and flow cytometrical characteristics.
Apoptotic bodies in the cerebellum of Japanese patients with Creutzfeldt–Jakob disease
Authors: Kawashima Toshiro , Doh‐ura Katsumi , Ogomori Koji , Iwaki Toru
Published: August 2010

The aim of this study was to provide morphological evidence for neuronal apoptosis in Creutzfeldt–Jakob disease (CJD) using hematoxylin‐eosin (HE)‐stained specimens. A microscopic examination showed typical apoptotic bodies were found in the granular layer of the cerebellum in 13 of 14 Japanese patients with CJD, while no apoptotic bodies were observed in any other areas of the examined CJD brains. Most of the fragmented nuclei of the apoptotic cells were labeled by in situ end‐labeling of fragmented DNA, terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick‐end labeling. To the authors' knowledge, this is the first report demonstrating neuronal apoptotic bodies in the human neurodegenerative disorders on HE‐stained sections. The present findings indicate that apoptosis plays a major role in the neuronal loss of the cerebellar granule cells in CJD.
Bottom‐up cell proliferation with cyclin A and p27Kip1 expression in ulcerative colitis‐associated dysplasia
Authors: Mikami Tetuo , Yoshida Tsutomu , Shiraishi Hiroaki , Tokuyama Wataru , Motoori Tadashi , Okayasu Isao
Published: August 2010

To analyze the cell kinetics of ulcerative colitis (UC)‐associated dysplasia, cyclin A, cyclin D1, cyclin E, cdk2, cdk4, p21Waf1, and p27Kip1 were immunohistochemically examined, in comparison with sporadic tubular adenomas. Immunohistochemical labeling indices for each marker in formalin‐fixed paraffin‐embedded tissue sections were assessed in a total of 23 low‐grade dysplasias, 27 high‐grade dysplasias, and 14 invasive adenocarcinomas associated with UC. For comparison, 21 sporadic tubular adenomas with low‐grade dysplasia, 33 with high‐grade dysplasia, and 21 invasive adenocarcinomas were also examined. In UC‐associated dysplasias, cyclin A and p27Kip1 were located in the lower parts of the crypts and p21Waf1 in the upper regions. In tubular adenomas, cyclin A, cdk4, p27Kip1, and p21Waf1 were all expressed in the upper parts of the crypts. The expression levels of cyclin D1, cyclin E, and cdk2 were low. The cell proliferation zone in UC‐associated dysplasia is located towards the bases of the crypts with the strong expression of cyclin A and p27Kip1, in contrast to tubular adenomas, which have their cell proliferation zone in the upper parts of neoplastic crypts. It is considered that tumorigenesis with UC‐associated dysplasia is of the bottom‐up type, related to altered expression of cyclin A and p27Kip1.
Characterization of biliary intra‐epithelial lymphocytes at different anatomical levels of intrahepatic bile ducts under normal and pathological conditions: Numbers of CD4+CD28– intra‐epithelial lymphocytes are increased in primary biliary cirrhosis
Authors: Isse Kumiko , Harada Kenichi , Sato Yasunori , Nakanuma Yasuni
Published: August 2010

Distribution of intra‐epithelial lymphocytes along intrahepatic biliary tree (bIEL), and their density and phenotype were examined in normal and diseased livers, particularly in primary biliary cirrhosis (PBC). Immunohistochemically, bIEL were examined in 28 normal livers, 13 cases of chronic viral hepatitis (CVH), 13 cases of PBC, five cases of primary sclerosing cholangitis (PSC), seven cases of extrahepatic biliary obstruction (EBO), and 16 hepatolithiatic livers. In normal livers, bIEL were relatively dense at large and septal bile ducts compared to interlobular ducts. Most of them were positive for CD3 and CD8, while a few were positive for CD4, CD20 and CD57. In CVH, PSC and EBO, neither distribution, phenotype nor density of bIEL differed from normal liver. In hepatolithiasis, numbers of CD8+bIEL were increased in stone‐containing ducts. In PBC, numbers of CD4+CD28–bIEL, which are reportedly responsible for target tissue destruction in autoimmune diseases, were markedly increased in damaged interlobular ducts. In conclusion, CD3+CD8+bIEL may be involved in immune homeostasis of intrahepatic bile ducts in normal livers and in CVH, PSC and EBO. Altered distribution and phenotypes of bIEL in PBC and hepatolithiasis may reflect their participation in biliary lesions. Increased CD4+CD28–bIEL in damaged bile ducts of PBC may be related to immune‐mediated biliary damage.
Multiple extranodal follicular dendritic cell tumors initially presenting in the soft tissue in the chest wall
Authors: Kawasaki Takashi , Watanabe Gen , Hasegawa Go , Naito Makoto
Published: August 2010

A follicular dendritic cell (FDC) tumor that involved the soft tissue of the chest wall, liver and thyroid was reported in a 72‐year‐old Japanese man. A biopsy specimen from the chest wall showed an uncommon malignant soft‐tissue tumor. No distinct immunohistochemical reactions were found. The patient died 1 year after the initial presentation. No definite diagnosis was given until autopsy was performed. Upon autopsy, each tumor was well‐circumscribed and a solid tan‐gray color on cut section. Microscopically, the tumor cells were composed of oval to spindle cells arranged in a short fascicular growth pattern. The autopsy specimen from the soft tissue of the chest wall had a strong reaction for CD21/CD35 and clusterin, a new FDC marker, whereas the biopsy specimen had an undistinct reaction for CD21/CD35 and a weak reaction for clusterin. FDC makers assisted in this diagnosis, especially with the autopsy specimen. In conclusion, it was difficult to diagnose an FDC tumor because of the particular tumor sites involved, lack of characteristic microscopic features, and because of aggressive tumor behavior.
Hepatocellular carcinoma with silent and cirrhotic non‐alcoholic steatohepatitis, accompanying ectopic liver tissue attached to gallbladder
Authors: Ikeda Hiroki , Suzuki Michihiro , Takahashi Hideaki , Kobayashi Minoru , Okuse Noriaki , Moriya Hitonobu , Koike Junki , Maeyama Shiro , Yotsuyanagi Hiroshi , Itoh Fumio
Published: August 2010

A 70‐year‐old man had been obese since youth. He had been treated for hypertension and diabetes mellitus. An abdominal ultrasound showed a mass in the liver. He was admitted to St Marianna University School of Medicine Hospital for further evaluation. There was no history of alcohol use, and hepatitis viral markers and autoantibodies were all negative. Several imaging studies showed overt hepatocellular carcinoma (HCC). Transcatheter arterial embolization was performed, followed by surgical resection. Histopathological examination revealed moderately differentiated HCC. The non‐tumor areas had pseudolobules in a diffuse pattern similar to alcoholic cirrhosis. The histological findings in the ectopic liver tissue attached to the gallbladder, which was also resected during surgery, were that there was no cirrhosis, but fine fibrosis with inflammatory cell infiltration of sinusoids. These findings were consistent with non‐alcoholic steatohepatitis (NASH). There was probably a progression of similar findings that had developed into cirrhosis. These findings confirmed a diagnosis of HCC, cirrhosis, and underlying NASH in this patient. The present case is important for investigation of the development into cirrhosis and carcinogenesis of NASH. The present case demonstrates the importance of evaluating obese patients with fatty liver for underlying NASH and ongoing follow up for development of cirrhosis and HCC.
Malignant perivascular epithelioid cell tumor of the colon: Report of a case with molecular analysis
Authors: Yamamoto Hidetaka , Oda Yoshinao , Yao Takashi , Oiwa Toshio , Kobayashi Chikashi , Tamiya Sadafumi , Kawaguchi Ken‐ichi , Hino Okio , Tsuneyoshi Masazumi
Published: August 2010

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal neoplasm, and malignant cases are extremely rare. A case of malignant PEComa arising in the colon is described herein. The patient was a 43‐year‐old Japanese woman without a history of tuberous sclerosis complex. The tumor occurred in the abdominal cavity attached to the serosal side of the descending colon. Histologically, the tumor consisted of sheets or closely packed nests of epithelioid cells with clear or eosinophilic cytoplasms. The tumor cells were positive for HMB‐45 but negative for S‐100 protein and cytokeratins by immunohistochemical staining. Ki‐67 labeling index was 2.9%. Peritoneal dissemination of tumor occurred at 20 months and the patient died of tumor at 38 months after the initial operation. This was considered to be a case of malignant PEComa, based on the histological and clinical features. Tumor cells showed overexpression of cyclin D1 but lacked the loss of heterozygosity of the TSC1 and TSC2 genes. The result suggests that the overexpression of cyclin D1 may play an important role in the tumorigenesis of PEComa. Because PEComas can behave in an aggressive manner, careful follow up is warranted.
Pathology of gastrointestinal stromal tumors
Authors: Hirota Seiichi , Isozaki Koji
Published: August 2010

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. It was found that most GIST expressed KIT, a receptor tyrosine kinase encoded by protooncogene c‐kit. In normal gastrointestinal wall, KIT is expressed by interstitial cells of Cajal (ICC), which are a pacemaker for autonomous gastrointestinal movement. Because both GIST and ICC are double‐positive for KIT and CD34, and because familial and multiple GIST appear to develop from diffuse hyperplasia of ICC, GIST are considered to originate from ICC or their precursor cells. It was also found that approximately 90% of the sporadic GIST have somatic gain‐of‐function mutations of the c‐kitgene, and that the patients with familial and multiple GIST have germline gain‐of‐function mutations of the c‐kitgene. These facts strongly suggest that the c‐kitgene mutations are a cause of GIST. Approximately half of the sporadic GIST without c‐kitgene mutations were demonstrated to have gain‐of‐function mutations in platelet‐derived growth factor receptor‐α (PDGFRA) gene that encodes another receptor tyrosine kinase. Because KIT is immunohistochemically negative in a minority of GIST, especially inPDGFRAgene mutation‐harboring GIST, mutational analyses of c‐kitandPDGFRAgenes may be required to diagnose such GIST definitely. Imatinib mesylate was developed as a selective tyrosine kinase inhibitor. It inhibits constitutive activation of mutated KIT and PDGFRA, and is now being used for KIT‐positive metastatic or unresectable GIST as a molecular target drug. Confirmation of KIT expression by immunohistochemistry is necessary for application of the drug. The effect of imatinib mesylate is different in various types of c‐kitandPDGFRAgene mutations, and the secondary resistance against imatinib mesylate is often acquired by the second mutation of the identical genes. Mutational analyses of c‐kitandPDGFRAgenes are also significant for prediction of effectiveness of drugs including newly developed agents.
Significance of chemoprevention for prostate cancer development: Experimental in vivo approaches to chemoprevention
Authors: Shirai Tomoyuki
Published: August 2010

Prostate cancer is the most common tumor in men in Western countries and mortality in Asian countries from the disease appears to be constantly increasing. Characteristics include (i) frequent discovery of latent carcinoma, even in countries with low incidences of clinical cancer; (ii) very long time to clinically significant cancer; (iii) few patients under 50 years of age (primarily a disease of elderly men); (iv) strong influences of environmental factors such as food; (v) temporal effectiveness of androgen deprival therapy; and (vi) no effective therapeutic approaches once hormone‐refractory neoplasms have developed. Therefore prostate cancer is particularly indicated for preventive efforts, especially chemoprevention. Several large‐scale chemoprevention trials have in fact been conducted and some have found suppressive effects. However, not all have been proven to have benefit. Experimental preclinical investigations, particularly using animal models, are recommended to find better chemopreventive agents with less adverse effects. Data using rat models have generated very interesting findings from which mechanism‐based strategies can be proposed. In the present report the importance of chemoprevention of prostate cancer will be discussed using the data on human and rat prostate cancer development.
Role of the PI3K/Akt, mTOR, and STK11/LKB1 pathways in the tumorigenesis of sclerosing hemangioma of the lung
Authors: Amin Randa M. S. , Hiroshima Kenzo , Miyagi Yohei , Kokubo Takeshi , Hoshi Kazuei , Fujisawa Takehiko , Nakatani Yukio
Published: August 2010

Although the histogenesis of sclerosing hemangioma (SH) of the lung is now thought to be respiratory epithelial in origin, the genetic abnormalities that mediate its development are not known. Because pathophysiology of several syndromes associated with benign tumors may converge on the tuberous sclerosis complex (TSC), serine/threonine kinase 11 (STK11), and mammalian target of rapamycin (mTOR) pathways, the purpose of the present paper was to investigate their roles in the development of SH. Semiquantitative immunohistochemical analysis was done to assess the expression of phospho‐mTOR, phospho‐S6 ribosomal protein, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phospho‐Akt, STK11, tuberin, hamartin, vascular endothelial growth factor (VEGF), and hypoxia‐inducible factor‐1α (HIF‐1α) in 19 cases of typical SH. To determine whether genetic alteration of STK11 is involved in the development of SH, all encoding exons of STK11 were analyzed by polymerase chain reaction (PCR) amplification and direct sequencing of genomic DNA of six specimens. The six specimens were also investigated for whether promoter hypermethylation exists as an alternative inactivating mechanism for STK11. All specimens showed moderate to marked reaction to phospho‐S6 ribosomal protein and PTEN; 16 specimens (84%) showed slight to moderate reaction to phospho‐mTOR, negative reaction to STK11, and slight to moderate reaction to hamartin; 11 (58%) showed slight to moderate reaction to phospho‐Akt; 18 (95%) showed slight to moderate reaction to tuberin and positive reaction for HIF‐1α; and 17 (90%) showed moderate reaction to VEGF. No somatic mutation of STK11 was found and the six specimens were unmethylated in the promoter region. These data imply that aberrant mTOR signaling may play a role in the development of SH, and its vascular nature may be due partially to high levels of VEGF caused by dysregulation of mTOR signaling.
Prognostic significance of gastric cancer metastasis in second‐tier lymph nodes detected on reverse transcriptase–polymerase chain reaction and immunohistochemistry
Authors: Ikeda Satoshi , Funakoshi Naoya , Usui Shinsuke , Takiguchi Noriaki , Hiranuma Susumu , Shibata Toshikatsu
Published: August 2010

To determine the prognostic significance of the methods used to determine the presence of metastasis in second‐tier lymph nodes of patients with gastric cancer, the authors studied lymph nodes surgically removed from 100 patients with gastric cancer (55 with early cancer, 45 with progressive). The results of HE staining were compared with those of immunohistochemistry using the anticytokeratin (CK) antibody and reverse transcriptase–polymerase chain reaction (RT‐PCR) assays. Lymph node 7 or 8a was obtained intraoperatively, then mRNA was extracted using an immunobeads method, and RT‐PCR with CK19 mRNA was performed. The P for Cox regression analysis for metastasis detected by HE staining, CK staining, and RT‐PCR of all 100 cases was 0.312, 0.426, and 0.021, respectively, while for second‐tier lymph nodes it was 0.154, 0.013, and 0.006, respectively. In conclusion, RT‐PCR and CK staining for detection of metastasis in second‐tier lymph nodes were more reliable prognostic indicators than conventional HE staining.
Carcinoid tumor of the renal pelvis: Consideration on the histogenesis
Authors: Kuroda Naoto , Katto Kazunobu , Tamura Masato , Shiotsu Tomoyuki , Hes Ondrej , Michal Michal , Nagashima Yoji , Ohara Masahiko , Hirouchi Takashi , Mizuno Keiko , Hayashi Yoshihiro , Lee Gang‐Hong
Published: August 2010

Carcinoid tumor of the renal pelvis is an extremely rare neoplasm and only two cases have been previously reported in the English‐language literature. Reported herein is a third case of carcinoid tumor arising in the renal pelvis. The tumor extending from the left renal pelvis into the left kidney was incidentally found in a 55‐year‐old Japanese woman. Macroscopically, the tumor was predominantly located in the dilated renal pelvis and was grayish‐white on cut surface. Microscopically, neoplastic cells proliferated with a ribbon‐like, trabecular, tubular and solid pattern. Furthermore, the tumor focally invaded the kidney parenchyma. No precursor lesion of neuroendocrine tumor was observed in the peripheral urothelial epithelium. Neither urothelial carcinoma nor teratoma component was observed within the tumorous mass. The cytoplasm of neoplastic cells was focally positive for Grimelius stain and focally positive for chromogranin A and synaptophysin. However, no neoplastic cells reacted with cytokeratins 7 and 20. Ultrastructurally, neoplastic cells contained dense core granules in the cytoplasm. Urologists and pathologists should recognize that carcinoid tumor may arise from the renal pelvis.
LKB1 protein expression in neuroendocrine tumors of the lung
Authors: Amin Randa Mahmoud Sobhi , Hiroshima Kenzo , Iyoda Akira , Hoshi Kazuei , Honma Koichi , Kuroki Motoo , Kokubo Takeshi , Fujisawa Takehiko , Miyagi Yohei , Nakatani Yukio
Published: August 2010

During a recent investigation of LKB1 gene abnormality in lung lesions, strong expression of LKB1 protein in normal neuroendocrine (NE) cells of the bronchial epithelium was found. Because LKB1 functions as a tumor suppressor gene, the question of whether alteration of LKB1 expression is related to the development of pulmonary NE tumors of various grades was investigated. LKB1 immunohistochemistry was examined in a total of 68 primary pulmonary NE tumors consisting of 30 specimens of small cell lung carcinoma (SCLC), 23 large cell neuroendocrine carcinomas (LCNEC), two atypical carcinoids, and 13 typical carcinoids. Loss or low expression (<20% immunoreactive cells) of LKB1 protein expression was more frequently observed in high‐grade NE tumors (SCLC and LCNEC; 45/53, 84.9%) than in typical and atypical carcinoids (3/15; 20%). The difference in LKB1 immunoreactivity between the high‐grade NE tumors and the carcinoid group was statistically significant (P < 0.0001). In conclusion, marked reduction of LKB1 expression in high‐grade NE tumors of the lung suggests a possible role of LKB1 inactivation in its tumorigenesis. Although a few previous studies indicated rare genetic alterations of LKB1 in SCLC, further studies including analysis of other NE tumors and focusing on epigenetic abnormalities of LKB1 gene are warranted.