bluuebunny/crossref_metadata_2025 huggingface dataset:
Adenosquamous carcinoma of the gall‐bladder with gastric foveolar‐type epithelium
Authors: Nishihara Kazuyoshi , Takashima Masaki , Furuta Toshiya , Haraguchi Masaru , Tsuneyoshi Masazumi
Published: December 2008

An 80 year old Japanese man had adenosquamous carcinoma of the gall‐bladder characterized by an adenocarci‐noma (AC) in the gall‐bladder lumen and a squamous cell carcinoma (SCC) in the Invaded region of the liver. In the AC, the tumor cells consisted of atypical columnar epithelium with pseudostratification, mimicking gastric foveolar epithelium, while atypical signet‐ting cells were scattered within the SCC. There was an abrupt transition between the AC and SCC areas. The tumor cells in the AC area were intensely positive for galactose oxidase‐Schiff staining, and paradoxical concanavalin A staining revealed these tumor cells to have Class II mucins. lmmunohistochemically, the tumor cells in foveolar‐type adenocarcinoma were diffusely positive for cathepsin D. Flow cytometrical analysis of DNA content showed the AC area to be diploid and the SCC area to be aneuploid. The Sphase fraction of the SCC area (46.9%) was larger than that of the AC area (19.5%). The positive rate of immunostaining for proliferating cell nuclear antigen in the SCC area (mean 50.627%) was larger than that of the AC area (mean 3.048%, P < 0.01). These resutts suggest that the AC area of this tumor, histochemically and immunohistochemically, showed gastric foveolar‐type characteristics, the SCC component was squamous cell metaplasia of the preexisting AC, and that the SCC area had a greater proliferating capacity than the AC area.
Immunohistochemical analysis of giant cell glioblastoma
Authors: Katoh Masahito , Aids Toshimitsu , Sugimoto Shinji , Suwamura Yutaka , Abe Hiroshi , Isu Toyohiko , Kaneko Sadao , Mitsumori Kenji , Kojima Hideaki , Nakamura Nishio , Nagashima Katuo
Published: December 2008

Giant cell glioblastoma (GCG) is one of a group of rare tumors in which the cell population is abnormally large and includes multinucleated cells of gigantic sizes. Immunohistochemical studies were performed on four GCG cases and found that all giant cells and/or tumor cells were positive for glial fibrillary acidic protein (GFAP), S‐100 protein, and vimentin, thus verifying the tumor's glial origin. The nuclei of multinucleated giant cells of three adult cases were frequently immunostained for proteins expressed during the cell cycle (proliferating cell nuclear antigen (PCNA) and Ki‐67), thereby demonstrating the proliferative capacity of these cells. By contrast, those of a 12 year old girl expressed these cell cycle markers rather infrequently. Alpha I‐anti‐trypsin was detected with relatively high frequency in the giant cells, and its presence may explain their bizarre sizes and pericellular reticulin fiber formation. A literature review of 32 cases revealed that the GCG that occurs preferentially in young girls is a type of pleomorphic xanthoastrocytoma. By contrast, GCG in adult males has the same age incidence as ordinary glioblastomas and, as these, expresses high levels of cell cycle‐related proteins. Thus, GCG, which is subclassified morphologically as ordinary glioblastoma, has distinct biological and clinical characteristics, with that in children requiring re‐evaluation because of its similarities to pleomorphic xanthoastrocytoma.
Malignant fibrous histiocytoma of the right ventricle of the heart
Authors: Teramoto Norihiro , Hayashi Kazuhiko , Miyatani Katsuya , Miyake Kenji , Sarker Ashit Baran , Tadashi Yoshino , Takahashi Kiyoshi , Akagi Tadaatsu , Sunami Hiroshi , Nawa Sugato
Published: December 2008

Right‐sided cardiac malignant fibrous histiocytoma (MFH) is extremely rare, and to the authors' knowledge only three cases have been reported. In this study, a case of MFH in the right ventricle, the septum, and the pulmonary valves and artery in a 47 year old male is described. The tumor showed typical pathological features of MFH, such as cellular pleo‐morphism, storiform pattern and abundant mitoses. Immu‐nohistochemical and electron microscopical findings were compatible with MFH, and excluded the possibility of leio‐myosarcoma and angiosarcoma. Whole body examination, including Gallium scintigram, localized the primary site to the heart. The details of this case are presented with a review of the reported cases of cardiac MFH.
Ioss of basement membranes in the invading front of O‐1N, hamster squamous cell carcinoma with high potential of lymph node metastasis: An immunohistochemical study for laminin and type IV collagen
Authors: Kobayashi Yutaka , Nakajima Tamio , Saku Takashi
Published: December 2008

The change in immunohistochemical localization of the two basement membrane molecules, laminin and type IV collagen, was studied in relation to tumor growth and lymphatic invasion in the transplanted hamster squamous cell carcinoma, O‐1N, that has a high potential of lymph node metastasis. At 1 week after transplantation, the tumors consisted of large round‐shaped nests of approximately 200 mm in diameter, 80% of which were encircled by continuous laminin and type IV collagen positive lines representing the basement membrane. At 5 weeks, however, the tumor cell nests became half in diameter with invasion in small islands or cords at the periphery and only 40% of them had continuous basement membrane. At 10 weeks, the basement membranes were disrupted in varying degrees in approximately 90% of the tumor cell nests. The disruption was most conspicuous on the outer and invading side of the nests. Lymphatic invasion and lymph node metastasis were observed in animals after 5 weeks of transplantation and the immunoreactivity was absent around tumor cell clusters growing in lymphatic spaces. The findings indicate that the disappearance of basement membrane and reduction in size of tumor cell nests are essential signs for local invasion of tumor cells leading to lymphatic invasion and metastasis to regional lymph nodes.
Incidence and distribution of isolated atrial amyloid: Histologic and immunohistochemical studies of 100 aging hearts
Authors: Kawamura Shunji , Takahashi Mutsuo , Ishihara Tokuhiro , Uchino Fumiya
Published: December 2008

The incidence and anatomic distribution of isolated atrial amyloid (IAA) in 100 aging hearts were studied histologically and immunohistochemically using antibodies against α‐human‐atrial natriuretic peptide (α‐ANP), human transthyre‐tin (TTR) and human amyloid P component (AP). Ninety‐one of 100 hearts (91%) had amyloid deposits in the atria. Amyloid deposits in all 91 hearts reacted with α‐ANP and AP antisera, and in four hearts other amyloid deposits that reacted with lTR antiserum were coincidentally seen in the atria. The prevalence of IAA deposition, using a semiquantitative evaluation, was significantly higher in the hearts from patients over 80 years of age, from women, those weighing over 450g, with a thickened left ventricular wall (>1.4 cm) and with multiple myocardial scars. IAA deposition showed a significant distribution in the auricle and left atrium; it was located mostly in the interstitium of the subendocardial layer and the subendorcardial myocardium. These results indicate that IAA occurs more frequently than previously appreciated in the elderly and in patients with certain cardiac disorders.
Growth patterns and interstitial invasion of small hepatocellular carcinoma
Authors: Tomizawa Minoru , Kondo Fukuo , Kondo Yoichiro
Published: December 2008

Twenty‐five caw of small hepatocellular carcinoma (HCC; dhmeter ≥30mm) were evaluated for overall morphologic features and growth patterns. The tumors often showed a uelldtfferentlated, normotrabecular histologic pattern and insidious interstitial invasion, which resembled benign hepetocytes scattered in connective tissues. As the tumor grew, B less‐differentiated tumor area became predominant. Portal tracts Included in small HCC nodules were quantitatively assessed, revealing that they progressively reduced in number with tumor growth. The tumor margin was often reported to be unclear. The present results indicate that the histologk grade of tumor differentiation, capsular formation, existence of liver cirrhosis and patterns of interstitial invaslon are important factors for determining the nature of the margin. The score of argyrophilic nuclear organizer regions (AgNOR) was examined in 5 cases showing typical interstitial imaslon with the insidious type. In each case, the AgNOR score of the invading tumor cells was lower than that of turnor cells within the HCC nodules, but higher than benign hepatocytes in cirrhotic parenchyma. It clarified that the growth activity of well‐differentiated HCC was rather suppressed upon their interstitial invasion.
The proliferating cell nuclear antigen (PCNA) index correlates with the grade of cytologic atypia in well‐differentiated early adenocarcinomas of the large intestine
Authors: Maeo Seigo , Ajioka Yoichi , Watanabe Hidenobu , Kobayashi Masaaki , Kobayashi Michio
Published: December 2008

Well‐differentiated colorectal adenocarcinomas are subclassified into carcinoma with high‐grade atypia (CAH) and carcinoma with low‐grade atypia (CAL) based on their cellular atypia. It is proposed that CAH and CAL are different in histologic prognostic factors and that the former should be regarded as carcinoma with high‐grade malignancy and the latter as low‐grade malignancy. In this study, the differences in cell‐proliferative activity between CAH and CAL were examined using a monoclonal antibody to the proliferating cell nuclear antigen (PCNA). The PCNA index and mitotic index of 27 early colorectal carcinomas (9 CAL, 5 CAH, and 13 carcinomas with mixed low‐ and highgrade atypia) was evaluated in relation to their depth of invasion. In intra‐mucosal lesions, both indices were higher in CAH (78%, 0.89%) than in CAL (68%, 0.47%; P <0.01). In lesions invading into the submucosa, the PCNA and mitotic indices were also higher in CAH (7596, 0.65%) than in CAL (35%, 0.19%; P <0.01). A significant correlation was observed between the PCNA index and the mitotic index in the mucosal lesions (P<0.05). These results indicate that CAH has a higher proliferative activity than CAL, and support the current authors' proposal that CAH is a high‐grade malignancy and CAL a low‐grade malignancy.
Environmental and genetic risk factors in early human atherogenesis: Lessons from the PDAY study
Authors: Strong Jack P. , Malcom Gray T. , Oalmann Margaret C.
Published: December 2008

A multi‐institutional study ‘Pathobiological Determinants of Atherosclerosis in Youth’ (PDAY) was initiated to document the natural history of atherosclerosis, its relationship to risk factors, and pathobiology of lesion development in young subjects. Pathology laboratories in nine centers collected arteries and tissues from over 2000 persons from 15 through 34 years of age whose deaths were attributed to homicides, accidents, or suicides. Arteries were evaluated for lesions, and risk factors were analyzed in a central laboratory. Postmortem risk factors included serum lipoproteins, serum thio‐cyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus (obesity), small renal artery changes (hypertension) and apoprotein isoforms. This study documents the development of atherosclerosis at an early age. It also shows that the recognized risk factors for coronary heart disease are associated with lesion development in the arteries of these young subjects. The PDAY study has a counterpart in Japan where the development of atherosclerosis has been studied in young subjects. This Japanese study, in a population in which coronary heart disease has not yet become a major epidemic, has findings quite similar to the findings from the PDAY study. Studies of atherosclerosis in both Japan and the USA provide strong justification for reducing risk factors in young persons.
Efficient and specific induction of esophageal tumors in rats by precursors of N‐nitrososarcosine ethyl ester
Authors: Xiang Yun‐Yan , Wang Dong‐Yu , Tanaka Masamitsu , Igarashi Hisaki , Kamo Takaharu , Shen Qiong , Sugimura Haruhiko , Kino Isamu
Published: December 2008

Cancers and precancerous lesions of the esophagus were efficiently induced in rats by the simulation of a clinico‐epidemiological setting; that is, the administration of precursors of nitrosamine. Six week old non‐inbred male Wistar rats were given 2g/kg bodyweight of sarcosine ethyl ester hydrochloride (SEEH) and concurrently 0.3g/kg bodyweight of sodium nitrite (NaNO2), precursors of N‐nitrososarcosine ethyl ester (NSEE), in 2% sucrose as drinking water. Group 1 received the precursors twice a week for 6 weeks followed by 8 weeks observation, and group 2, once every 3 days for 7 weeks followed by 26 weeks observation. At the end of treatment, no tumor had developed in the esophagus of rats in group 1, but the [3H]‐thymidine labeling indices in both basal and superficial layer cells were higher than in the control group. On subsequent observation, papillomas appeared in group 1 (33.3%), and carcinomas in group 2 (33.3%), within 4 weeks. The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When the observation was prolonged in group 2,100% of the animals had cancer in week 20. The pathological changes of the lesions paralleled the sequential development of human squamous cell carcinoma of the esophagus. Our system has the advantages in that papillomas and cancers can be induced in rats in a short time and the agents used are less toxic than preformed nitrosamines administered previously by gastric intubation. It would serve as a useful experimental tool to study premalignant lesions and cancers of the esophagus.
Pulmonary tumor thrombotic microangiopathy
Authors: Sato Yuichiro , Marutsuka Kousuke , Asada Yujiro , Yamada Manabu , Setoguchi Toshiaki , Sumiyoshi Akinobu
Published: December 2008

Pulmonary tumor thrombotic microangiopathy (PTTM) is characterized by widespread fibrocellular intimal proliferation of the small pulmonary arteries and arterioles in patients with metastatic Carcinoma. Microscopic pulmonary tumor emboll have frequently occurred in patients with malignant tumors; however, few cases of PTTM have been reported. A rare case of a patient with gastric adenocarcinoma who presented with acute dyspnea and lethal respiratory failure is described. Histologically, diffuse fibromuscular intimal thickening cauring luminal stenosis and obstruction but containing rather few cancer cells was observed in the small pulmonary arteries and arterioles. These findings were consistent with PTTM. Atthough PTTM is a rare phenomenon, PTTM should be considered in the differential diagnosis of acute dyspnea or pulmonary hypertension in patients with carcinoma.
Pleomorphic adenoma of the breast: Case report and review of the literature
Authors: Narita Takeo , Matsuda Keiji
Published: December 2008

A tumor of the right breast was noticed in a 70 year old female. The tumor was round, 1times1 cm, and was encapsulated with thin fibrous tissue. The boundary was clear. The cut surface showed a mosaic pattern of brown and white dots and the texture was gritty. Histologically, glandular structures, trabecular or solid epithelial cell nests, myxoid, cartilaginous and osteoid areas, and one ossifying focus were found. Round, polyhedral or fusiform myoepithelial cells proliferated around the glandular structures and were dispersing into the myxoid and cartilaginous tissue. Myoepithelial proliferation was especially marked around the small glandular structure. Immunohistochemically, S‐100 protein was strongly positive for the myoepithelial cells around the glandular structures and in the cartilaginous tissue. Until now, 54 cases of pleomorphic adenoma of the breast have been reported. In those cases, the subareolar region was a common site for the tumor, and pleomorphic adenoma was thought to arise from large ducts in this region. No Oriental patients have been reported in the literature.
T cell‐rich B cell lymphoma bearing Epstein‐Barr virus in tumor cells: A case of IBL‐T‐like lesion following Lennert's lesion
Authors: Wakatsuki Susumu , Yumoto Norio , Takagi Toshiyuki , Kurosu Katsusi , Sakai Chikara , Tamayama Chieko , Komatsu Teisuke , Matsuzaki Osamu , Mikata Atsuo
Published: December 2008

A case of T cell‐rich B cell lymphoma (TCRBCL) with Epstein‐Barr virus (EBV) infection in tumor cells is reported. A 50 year old male developed right cervical lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many scattered Hodgkinoid atypical cells with Lennert's lesion. After partial remission following chemotherapy, the lymph nodes enlarged again, and a second biopsy in February 1991 showed an IBL‐T‐like lesion. Only a small number of Hodgkinoid atypical cells were still observed. After apparently, complete remission, the lesion soon recurred and the patient died in November 1992. Immunohistochemically the Hodgkinoid cells were positive for L26, but negative for LN2, LN3, UCHL‐1, MT1, lysozyme, Ber‐H2 and Leu‐M1. Reactivity for immunoglobulins showed falsepositive because of poly‐clonal staining. IgH monoclonality was detected by the poly‐merase chain reaction method in the first biopsied specimen, and by Southern blotting in the second biopsied snap‐frozen specimen. Monoclonal TCRβ rearrangement was not detected. The Hodgkinoid atypical cells were positive for EBVencoding RNA by in situ hybridization, and LMP‐1 by immunostaining. Occasionally, EBV‐bearing immunoblastic, medium sized, or small lymphocytic cells were also observed. This case indicates the possibility that EBV is related to the pathogenesis of TCRBCL.
Alveolar basement membrane breaks down in diffuse alveolar damage: An immunohistochemical study
Authors: Matsubara Osarnu , Tamura Atsuhisa , Ohdama Shinichi , Mark Eugene J.
Published: December 2008

Sequential structural changes of the alveoli in diffuse alveolar damage (DAD) were examined by immunohistochemical methods. Lung specimens obtained at autopsy from 52 patients with DAD were stained with antibodies to laminin, 7S collagen (7S) and type IV collagen (type IV) for alveolar basement membrane, to von Willebrand factor, CD‐31 and thrombomodulin (TM) for the alveolar capillary endothelial cell, and to epithelial membrane antigen and surfactant apo‐protein (PE‐10) for the alveolar epithelium. Forty‐two of the patients had the exudative form of DAD; 10 of the patients had the proliferative form of DAD. The results were summarized as follows: (i) laminin was most easily impaired both in the epithelial and capillary basement membrane in the early exudative stage; (ii) following laminin, 7S and type IV in the capillary basement membrane were also injured in the early exudative stage, and recovered in the proliferative stage; (iii) subsequently, 7S and type IV in the epithelial basement membrane were also impaired in the late exudative stage, and remained impaired even in the proliferative stage; and (iv) alveolar epithelium regenerated almost completely in the late exudative stage, but staining for TM in the alveolar capillary recovered in the proliferative stage. Because the alveolar basement membrane must govern the homeostasig of alveolar tissue architecture, it was concluded that its preservation is necessary to avoid the abnormal remodeling of the alveoli in the reparative stage of DAD, if the patient survives the acute episodes of the disease.
Integrin distribution in gastric carcinoma: Association of β3 and β5 integrins with tumor invasiveness
Authors: Kawahar Ei , Ooi Akishi , Nakanishi Isao
Published: December 2008

Immunolocalization of a variety of integrins using monoclonal antibodies against β3, β5, α3β1 and α6, and polyclonal antibodies against vitronectin receptor (αvβ3) and l were investigated on PLP‐fixed paraffin sections of 19 cases of advanced gastric carcinomas. The β5 integrin, which pairs only with the av subunit, was positive in seven cases (37%), and was associated closely with scirrhous invasion (P < 0.05). β5 was positive chiefly in the cytoplasm of carcinoma cells and infrequently in cell membranes. β3, which is another subunit pairing with av, was positive in six cases (32%), and tended to be associated with scirrhous invasion (P < 0.1). β3 was also located chiefly in the cytoplasm. Five of the seven β5‐positive cases showed coexpression of β3. Polyclonal antibodies to αvβ3 also showed a significant difference among the amounts of stroma (P < 0.05). Anti‐β1 antibodies showed clear positivity in many cases (89%). Of the β1 integrins, α3β1 was positive in a few cases (26%) without any preferential pattern, and laminin receptor subunit α6 stained on cell membranes of neoplastic epithelia in many cases of carcinoma (89%) except for mucinous carcinoma. These distinctive patterns of integrin positivity indicate a close association of β5 and β3 expression with scirrhous invasion in gastric carcinoma.
Unsuccessful effort to detect human papillomavirus DNA in urinary bladder cancers by the polymerase chain reaction and in situ hybridization
Authors: Sano Takaaki , Sakurai Shinji , Fukuda Toshio , Nakajima Takashi
Published: December 2008

The association of human papillomavirus (HPV) with urinary bladder carcinogenesis is now a controversial issue. In order to certify the presence of HPV DNA in urinary bladder cancers, the polymerase chain reaction (PCR) using five primer sets for detecting various HPV types was used in this study as weli as in sltu hybridizetion (ISH) for HPV 16 and 18 detection. In the PCR study of 93 DNA samples extracted from formalin‐fixed and paraffin‐ernbedded urinary bladder cancem, no HPV DNA was detected in these tumor samples. The ISH study was also performed on the same tumor samples, but failed to demonstrate any HPV 16‐or 18‐positive signals in ail except one of the tumor samples. However, the FCR failed to demonstrate HPV 16 DNA even in the bladder cancer positive for HPV 16 DNA by the ISH. This ISH technique was able to demonstrate HPV 16 and 18 DNA in eight of 13 paraffinembedded cervical cancers, in which HPV 16 or 18 DNA had already been detected by the PCR. Our HPV study using PCR and ISH revealed that the HPV status of urinary bladder carcinomas was far different from that of cervical cancers.
Immunohistochemical and flow cytometric study of neuroendocrine carcinoma of the skin
Authors: Fukunaga Masaharu , Shinozaki Noboru
Published: December 2008

Immunohistochemical and flow cytometric analysis using formalin‐fixed, paraffin‐embedded sections was performed on 10 neuroendocrine carcinomas of the skin (NCS). Grim‐elius staining was positive in seven tumors. All tumors showed coexpression of CAM 5.2 and neuron‐specific enolase with paranuclear dot‐like or diffuse cytoplasmic reactivity. Neuro‐filament was positive in five cases, chromogranin in six, calcitonin and carcinoembryonic antigen in two each, and somatostatin and S‐100 protein in one each. Eight primary lesions were diploid and the remaining two were aneuploid; however, two diploid NCS presented as aneuploid metastatic tumors. The follow‐up periods ranged from 3 to 66 months (mean 13.6). Six patients died of metastatic diseases between 3 and 33 months (mean 9.2) after the diagnosis. There were no significant correlations among histologic features, DNA ploidy, S‐phase fraction, and clinical outcome of the patients with NCS. These results indicate that a panel of antibodies may be required for immunohistochemical confirmation of neuroendocrine differentiation and that a flow cytometric analysis is not a good tool to predict the biologic behavior of NCS.
Evolution of three patterns of intra‐alveolar fibrosis produced by bleomycin in rats
Authors: Usuki Jiro , Fukuda Yuh
Published: December 2008

In pulmonary fibrosis, it is known that fibrotic changes develop in the intra‐alveolar spaces and that intra‐alveolar fibrosis can be classified into three patterns, namely intraalveolar buds, mural incorporation and obliterative changes. In order to clarify the evolution of intra‐alveolar fibrosis, immunohistochemical studies of extracellular matrix proteins and electron microscopic observations were made of the lungs of rats given a single intretracheal instillation of bleomycin. All three patterns of fibrosis developed in this model. Intra‐alveolar buds changed into globular lesions with dense collagen deposition, the surface of which was covered by alveolar epithelium. Electron microscopy revealed that the buds often contained spiraling collagen fibrils and numerous microfibrils, but not mature elastic fibres, beneath the regenerating epithelial lining cells; the epithelial basement membranes were discontinuous. In contrast, mural incorporation and obliterative changes ware associated with alveolar structural remodeling. Electron microscopically, these lesions had bundles of normal collagen fibrils, small elastic fibers, and continuous epithelial basement membranes. These results indicate that: (i) intra‐alveolar buds, that become intra‐alveolar collagen globules, with an unusual extracellular matrix, do not contribute to alveolar structural remodelling; and (ii) areas of mural incorporation and obliterative changes have the usual type of extracellular matrix and are essential for alveolar structural remodeling.
Pericardial malignant mesothelioma: Case report and discussion of immunohistochemical and histochemical findings
Authors: Ohmori Takaaki , Arb Norimasa , OkActa Kazuyo , Kondo Mari , Tabei Ryo
Published: December 2008

An extremely rare case of malignant mesothelioma of the pdcardium is reported. The tumor appeared to be the Uphasic type of diffuse malignant mesothetioma which presgnt many small to tine lipid droplets in the cytoplasm, particularly that of the epithelial cell, and a positive immunohistochemical reaction with antibodies to low molecular weight cytokeratin (45–50 kDa) in all of the tumor cells. The literature is also reviewed and the presence of lipid droplets and the importance of the immunohistochemical positivity to low molecular weight cytokeratin for differential diagnosis from other malignant tumors, such as invasive adeno‐carcinoma or primary sarcoma of the pleura, or soft tissue sarcoma involving the pleura is discussed.
Immunohistochemical localization of C‐reactive protein‐binding sites in human atherosclerotic aortic lesions by a modified streptavidin‐biotin‐staining method
Authors: Hatanaka Kaoru , Li Xiang‐An , Masuda Kazuyoshi , Yutani Chikao , Yamamoto Akira
Published: December 2008

One‐step fluorescein‐conjugated polyclonal antibody technique has shown that C‐reactive protein (CRP) was located only extracellularly in human atherosclerotic lesions. In this report a more sensitive streptavidin‐biotin technique was applied to detect the localization of CRP in human athere sclerotic lesions. lmmunohistochemical staining with polyclonal and monoclonal anti‐human CRP antibodies both produced a brown color extracellularly in the necrotic lesions, and intracelluarly in CD68+ foam cells. The latter suggests an uptake of CRP‐lipid complexes by macro‐phages. The staining is human CRP‐specific because it was eliminated by preabsorption of the monoclonal antibody with pure human CRP, or by substitution of the primary antibody with non‐immune rabbit serum. By overlaid CRP‐binding study, a positive stain was observed on intimal smooth muscle cells and foam cells, suggesting that they have CRP‐binding sites unless the CRP‐binding activity was generated de novo through the fixation procedure. Accordingly, it is hypothesized that CRP may facilitate the uptake of lipids by macrophages accumulating in atherosclerotic lesions. Further, CRP might participate in cytolysis, which enlarges the necrotic area, and/or in phagocytosis that scavenges the necrotic tissue.
Structural characteristic of splenic sinuses in idiopathic portal hypertension
Authors: Maesawa Chihaya , Sakuma Tsutomu , Sato Takehiko , Masuda Tomoyuki , Muro‐oka Genyoh , Satodate Ryoichi
Published: December 2008

Splenic sinuses in idiopathic portal hypertension (IPH; 8 patients}, liver cirrhosis (LC; 14 patients) and in regenerating autotransplanted spleens from 25 rats were compared with each other by scanning electron microscopy (SEM) and immunohistochemistry using antibodies against proliferating cell nuctear antigen (PCNA). Spleens obtained from six patients with gastric carcinoma and from five untreated adult rats were examined as controls. SEM of the sinuses showed that in IPH endothelial cells became irregular in shape, and the interendothelial slits of sinuses were irregularly entarged. Sinus endothelial processes traversing the sinusal lumen were also found. The same changes were observed in the proliferating sinuses during regeneration of splenic tissue after autotransplantation in rats, but disappeared when the regeneration was completed. Irregular endothelial cells were few in LC. PCNA‐positive sinus endothelial cells were increased in number in IPH as compared with those in LC; the mean number of PCNA‐positive ones per cm2was 45.4 in IPH and 8.2 in LC. It was suggested that, from SEM observation of sinus endothelial cells and counting PCNA‐positive sinus endothelial cells, the sinuses of the spleen in IPH consist of proliferating endothelial cells or are in the state of increased proliferation. In conclusion, splenomegaly in IPH was presumed to be caused by proliferation of sinus endothelial cells, and by the increased splenic blood flow in the irregularly widened interendothelial slits of the sinuses.
Poorly differentiated (‘insular’) carcinoma of the thyroid
Authors: Mizukami Yuji , Nonomura Akitaka , Michigishi Takatoshi , Noguchi Masakuni , Ohmura Kenji , Nakamura Shinobu , Hoso Masahiro
Published: December 2008

Three cases of unusual poorly differentiated (‘insular’) carcinoma of the thyroid gland are presented. These three thyroid carcinomas were large; the tumors from patients 1 and 3 were encapsulated, and that from patient 2 showed invasive growth. Microscopically the tumors were characterized by welldefined solid nests (insulae), which were composed of rather small and uniform tumor cells with round to oval nuclei. Formation of small and colloid‐containing follicles was associated with these nests to varying degrees. The tumors of patients 1 and 3 were composed entirely of insular components, but that of patient 2 was associated with small areas of welldifferentiated follicular carcinoma. The metastatic tumors of patients 1 and 2 were essentially similar to the primary with small foci of follicular carcinoma.

Patient 1 is alive with local and mediastinal node recurrences, but patient 2 died of the disease with local recurrences and metastases to lungs, bones and skin. Patient 3 had no recurrences and died of unrelated disease 5 years after surgery. The present study indicates that insular carcinomas have characteristic histologic features and a less favorable prognosis, confirming the findings of previous studies.
Myoepithelial carcinoma in pleomorphic adenoma of salivary gland type, occurring in the mandible of an infant
Authors: Asai Satomi , Tang Xiaoyan , Ohta Yoshihide , Tsutsumi Yutaka
Published: December 2008

A rapidly growing mandibular tumor occurred in a 17 month old female infant. Tumor outgrowth showing a periosteal reaction was radiographically seen on the lower surface (base) of the mandible. Under the biopsy diagnosis of osteosarcoma, high‐dose chemotherapy with methotrexate was performed, resulting in little effect. The right hemiman‐dibulectomy specimen disclosed intraosseous infiltrative growth of pleomorphic adenoma of salivary gland type, associated with chondroid stroma and reactive bone formation. The highly proliferative small‐sized cells retained immunohistochemical features of myoepithelial cells, with positive reactivity of cytokeratin, vimentin, S‐100 protein, a‐smooth muscle actin, epithelial membrane antigen, CA15–3, type IV collagen, laminin and p53 protein. No heterotopia of the salivary gland was identified within the bone tissue. The tumor recurred 2 months later. Due to uncontrollable local growth, the patient died 8 months after operation. At autopsy, reactive ossification was closely associated with malignant myoepithelial proliferation. No distant metastasis was noted. This osteosarcoma‐like tumor can be regarded as myoepithelial carcinoma in pleomorphic adenoma, originating from intramandibular heterotopic salivary gland tissue.
Clear cell chondrosarcomas arising from rare sites
Authors: Ogose Akira , Motoyama Teiichi , Hotta Tetsuo , Emura Iwao , Inoue Yoshiya , Morita Tetsuro , Watanabe Hidenobu
Published: December 2008

Three cases are reported of clear cell chondrosarcoma arising from unusual sites: talus, rib and vertebra. Radio‐graphically, two tumors showed osteolytic features and the vertebral tumor showed osteoplastic change. Histologically, ell tumors consisted of clear cells that had a centrally piaced nucleus surrounded by clear cytoplasm, osteoclast‐like giant cells, am of conventional chondrosarcoma, and various amounts of reactive bone. The tumor in the talus was initially diagnosed as benign chondroblastoma, but it recurred. The rib tumor showed marked cystic formation stimulating aneurysmal bone cyst. The osteoplastic radio‐graphic feature in vertebral tumor was considered to be due to the abundant bone formation.
Ieiomyosarcoma of the superior vena cava producing superior vena cava syndrome and heart tamponade
Authors: Sumiyoshi Yoshiaki , Kikuchi Masahiro
Published: December 2008

An autopsy case of primary leiomyosarcoma arising in the superior vena cava is presented. A 44 year old Japanese man presented with superior vena cava syndrome and eventually died due to heart tamponade and acute renal failure. Autopsy revealed that the superior vena cava was occluded with a tumor that had invaded the pericardium and right thoracic cavity. Primary caval venous leiomyosarcoma is a rare but lethal disease and most cases arise from the inferior vena cava. This case represents a very rare case of leiomyosarcoma with the rare clinical findings of superior vena cava syndrome and heart tamponade.
Iocalization of Epstein‐Barr virus genome in lymphoid cells in poorly differentiated adenocarcinoma with lymphoid strorna of the colon
Authors: Vilor Mabel , Tsutsumi Yutaka
Published: December 2008

Poorly differentiated adenocarcinoma with lymphoid stroma occurred in the transverse colon of a 77 year old female. Numerous small lymphocytes and plasma cells were distributed in the tumor stroma. Non‐isotopic in situ hybridization study for Epstein‐Barr (EBV)‐related small nuclear RNA (EBER‐1) revealed positive signals in the nuclei of a few lymphocytes in the tumor stroma, while the tumor cell nuclei were not labeled. lrnmunostaining for latent membrane protein‐1 was negative. The significance of detection of the EBV‐infected lymphocytes in the colon tumor strorna is discussed.
Immunohistochemical study of hepatic angiomyolipoma
Authors: Nonomura Akitaka , Mizukami Yuji , Takayanagi Nobutatsu , Masuda Shinji , Ishii Keiko , Tashiro Kazuhiro , Mizoguchi Yoshikazu
Published: December 2008

An immunohistochemical study was performed on nine hepatic anglomyolipomas (AML) found in eight patients. Histologically, the tumors were fundamentally composed of the three heterogeneous tissue components of blood vessels, smooth muscle cells (SMC), and fat cells, although the proportions and distributions were quite variable from tumor to tumor and from area to area in the same tumor. Additionally, cellular pleomorphism and atypia with occasional bizarre giant cells were found in the SMC component. This histologic feature might lead to a mistaken diagnosis of malignant neoplasm, and pathologists should therefore be aware of the broad histologic spectrum of hepatic AML. However, the Immunostalning patterns were basically the same in all nine tumors. All tumor components were negative for epithelial membrane antigen (EMA) and for cytokeratin. The spindle‐shaped SMC component of the tumor was occasionally positive for vimentin, desmin and alpha‐smooth muscle actin, whereas epithelioid SMC were negative for all three. Both the epithelioid and spindle‐shaped SMC were occasionally positive for S‐100 and neuron‐specific enolase. All types of SMC in the tumor, whether spindle, epithelioid, intermediate or pleomorphic SMC, were strongly positive for HMB‐45, a melanoma‐specific monoclonal antibody. Fat cells were occasionally positive for S‐100. Endothelial cells were positive for factor Vlll‐associated antigen. Among hepatic tumors HMB‐45 reactivity is, so far as we know, found exclusively in the SMC of AML, and the HMB‐45 reactivity of a hepatic tumor is thus clearly an important piece of information in the diagnosis of AML
Apoptosis of colon cancers assessed by in situ DNA nick end‐labeling method
Authors: Ikenaga Makoto , Takano Yasuo , Saegusa Makoto , Ohtani Yoshimasa , Hiki Yoshiki , Kakita Akira , Okayasu Isao
Published: December 2008

Apoptosis in colon cancers was investigated using in situ DNA nick end‐labeling. Seventy‐six colon cancer cases were divided according to hlstologically defined malignant grading, degree of invasion and other pathologic Indicators. The apoptotic labeling index (ALI) was highest in cases with invasion limited to the submucosa, the difference as compared to other stages being statistically significant, while no correlation was noted between ALI and histological type. ALI significantly decreased with lymph node involvement of cancers. In contrast, there appeared to be no link with vessel invasion. ALI was significantly higher in lesions smaller than 2 cm in diameter. These results indicate that apoptosis In colon cancers is more frequent at a relatively early stage when the lesions are small, and suggest that the apoptotic phenomenon may play some role in regulating the size and progression of such tumors.
Overexpression of p53, c‐erbB‐2 and epidermal growth factor receptor in human breast carcinomas
Authors: Suzuki Masatsugu , Okuyama Takazo , Yoshikawa Kiyotsugu , Yamaoka Yoshio , Ariyasu Tetsuya , Fujita Masayuki , Tankawa Hidemttsu , Sugiyama Taketoshi , Takahashi Rei
Published: December 2008

Overexpression of pS3 protein, epidermal growth factor receptor (EGF‐R), and c‐erbB‐2 protein was assessed by immunohistochemlcai staining of formalin‐fixed, paraffin‐embedded tissue from 64 Invasive breast tumors. The correlation between abnormal expression of each protein and various disease parameters, including lymph node metastasis and histopathologic type and grade was analyzed. Despite the previous proposal, no significant correlation was found between lymph node metastases and overexpression of each gene in the primary tumors. In addition, some metastatic lesions did not always exhibit overexpression, even if it was evident In the primary tumors. Overexpression of c‐erbB‐2 protein correlated well with Bloom's histological grading. p53 expression was detected most often in tumors with hyperchromatlsm and more frequent mitosis. Over‐expression of c‐erbB‐2 protein occurred more frequently in p53‐positive tumors. The results Indicate that abnormal expression of p53 protein causes genetic instability in the early stage of tumor development, resulting In subsequent overexpression of other oncogenes.
Identification of the cell type origin of odontoma‐like cell masses in microphthalmic (mi/mi) mice byin situhybridization
Authors: Nakajima Yuko , Shimokawa Hitoyata , Terai Kunihiro , Onoue Hitoshi , Seino Yoshiki , Tanaka Hiroyuki , Sobue Shizuo , Kitamura Yukihiko , Nomura Shintaro
Published: December 2008

Tooth abnormalities occur in microphthalmic (mi/mi) mice. The elongated odontogenlc epithelium is interrupted by un‐resorbed bone at the basal end of themi/miIncisor, with the epithelium gathered into cell clusters. These clusters develop to odontoma‐like masses. To identify the origin of the cell types of these odontoma‐like masses, the localization of osteonectin (Osn), osteocalcin (Osc), osteopontin (Osp), matrix Gla protein (MGP) and amelogenin (Am) mRNA in the process of tooth development inmi/miand +/+ mice was investigated by means ofin situhybridization. Decalcified mandibles of neonatal, 5‐, 10‐, 14‐day‐old mice were examined. Osn and Osc mRNA, which localized in osteoblasts and odontoblasts, were also detected in the cells of odontoma‐like masses inmi/mimice. The cells expressing these mRNA were short, columnar and odontoblast‐like. Am mRNA was detected In ameloblasts. Inmi/mimice, Am mRNA was also detected in ameloblastic cell clusters, which were formed by the tall columnar cells in the odontoma‐like masses. No apparent Osp mRNA expression was detected in the masses. These results indicated that even In odontogenlc abnormal cells resulting from physical obstruction inmi/mimice, the genes that are involved in normal tooth development were still expressed.
Enhanced CD34 expression of sinusaid‐like vascular endothelial cells in hepatocellular carcinoma
Authors: Cui Shunjin , Hano Hiroshi , Sakata Akihiko , Harada Toru , Liu Tiecheng , Takai Shigeharu , Ushigomey Shinichiro
Published: December 2008

The immunohistochemlcal expression of CD34 (human hematopoletic stem cell and endothelial cell marker) and laminin were studied In chronic liver diseases and hepate cellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non‐cancerous slnusoids and sinusoid‐like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and lami‐nin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and petinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid‐like tumor vessels. However, early‐stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid‐like vessels. Laminin was strongly expressed in advanced HCC but not in early‐stage HCC. The results Indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothellal cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.
Expression of apoptosis, proliferating cell nuclear antigen, and apoptosis‐related antigens (bcl‐2, c‐myc, Fas, Lewis and p53) in human cholangiocarcinomas and hepatocellular carcinomas
Authors: Terada Tadarhi , Nakanuma Yasuni
Published: December 2008

In situ expression of apoptosis and its related antigens has rarely been evaluated in human liver tumors. Therefore, Investigation using in situ nick end‐labelling and Immunohistochemical methods of the in situ expression of apoptosis, prollferating cells, and apoptosis‐related antigens in 7 normal livers, 20 cholanglocarclnomas (CC) and 17 hepatocellular carclnomas (HCC) was done. Apoptotlc cells as determined by the nick end‐labelling method and proliferating cell nuclear antigen‐positive cells were present in all specimens, and the percentage of them was significantly higher in CC than In HCC. Bcl‐2 protein was present only in one CC e+nd one HCC, but was occasionally noted in bile ducts in non‐cancerous livers. C‐myc and Fas antigens were not found in any of the cases. Lewisy antigen was expressed In 8 CC, but was absent in the other cases although bile ducts In non‐cancerous livers frequently expressed Lewisy. p53 protein was present in 8 CC, but was absent in the other cases. Serial section observation showed that apoptotic cancer cells ware consistently negative for proliferating cell nuclear antigen; bcl‐2‐positive cells did not show apoptosis; p53‐positive cancer cells showed apoptosis. Some Lewisy positive cancer cells showed apoptosis, while others did not. These data suggest that apoptosis and cell proliferation are lnvolved in CC and HCC, and their degree is more severe in CC than In HCC. p53 protein (stimulative) may regulate apoptosis in some cases, whereas c‐myc, Fas and Lewisy are not relatad to apoptosb In CC and HCC in vivo. Many other factors may regulate apoptosis in CC and HCC in vivo.
Melanocytes in malignant ameloblastoma
Authors: Takeda Yasunori
Published: December 2008

An unusual case of malignant ameioblastoma which transformed a pre‐existing benign lesion In the maxilla of a 63‐year‐old Japanese female is reported. In addition to the characteristic histopathological features of less‐differentiated malignant ameloblastoma, dendritic‐shaped cells containing various amounts of melanin pigment were distributed in the tumor nests invading bone and soft tissue around the maxillary antrum, and some tumor cells containing melanin granules in their cytoplasm were also noted. Neither melanocytes nor melanin pigments were seen within the stroma Although no firm conclusion of the possible histogenesis of melanocytes in the present case could be drawn, this is the flrst case of odontogenic epithelial tumor with melanocytosis.
Primary adenocarcinoma of the renal pelvis with special reference to histochemical observations
Authors: Tsuzukl Toyonori , Kouketsu Hiroshi , Ono Kenzo , Kobayashi Hiroaki , Obata Koji
Published: December 2008

A case of adenocarcinoma of the renal peivis is presented. The patient was an 84‐year‐old man suffering from longstanding right‐sided nephrolithiasis. Surgical resection of the right kidney revealed adenocarcinoma with slight stromal invasion. A tubulovillous adenoma, which was morphologically similar to an adenoma of the large Intestine, was also found adjacent to the adenocarcinoma. The pelvic epithelium neighboring the lesion revealed Intestinal metaplasla. Histochemical studies revealed that the tumor In the patient and adenocarcinomas or adenomas of the large intestine have similar properties of cytoplasmic mucin. These findings suggest that the epithelium with intestinal metaplasia may have developed into the adenoma and flnally transformed into the adenocarclnoma. In addition, only tumor cells with severe atypia, most of which morphologically corresponded to adenocarcinoma, demonstrated positive nuclear staining for anti‐p53. This suggests that p53 may play an important role In the malignant transformation of adenomas into adenocarcinomas, as is the case in the large intestine.
Electron microscopic study of chronic eosinophilic pneumonia
Authors: Saitoh Kiyoshi , Shindo Noboru , Toh Yasuo , Yoshizawa Atsuto , Kudo Koichiro
Published: December 2008

Two cases of chronic eoslnophlllc pneumonia were examined electron mlcroscoplcally to study the role of eosinophll granulocytes. Eoslnophlls, together wlth macrophages and lymphocytes, were observed to have Infiltrated prominently in the lung tissues of the two cases. Degeneration and necrosis of pneumocytes were observed, and denuded basement membranes and destroyed alveolar structures were occasionally found. In the alveolar septa, swelling of the endothellal cells of the blood caplllarles, edema of the stroma and fibrin deposition were observed. Eosinophils, released eosinophil granules and macrophages phagocytosing eosinophll granules were found frequently near the degenerated and necrotic alveolar tissues. These findings suggest that the tissue injuries were induced by the cytotoxic effects of the eosinophil granules.