bluuebunny/crossref_metadata_2025 huggingface dataset:
Epstein‐Barr virus‐positive multiple early gastric cancers and dysplastic lesions: A case report
Authors: Arikawa Junkou , Tokunaga Masayoshi , Tashiro Yukie , Tanaka Sadao , Sate Eiichl , Haraguchi Kaname , Yamamoto Arihiro , Toyohira Osamu , Tsuchimochi Akio
Published: December 2008

Epstein‐Barr vlrus (EBV) has been implicated as a causal virus of gastrlc cancer with episomal monoclonality, elevated antibodles and a unlque morphologlc expression in the early intramucosal stage, but the infection mechanisms have not been demonstrated. EBV has been shown only in the cancerous lesions by the highly sensltlve EBVencoded small RNA in situ hybridization (EBER‐ISH) method, not in the dysplastic mucosa adjacent to the cancer. A case is presented of multiple EBV‐positive gastric cancer and dysplastic epithelium observed In a 52‐year‐old man. Serlai cut sections of the gastrectomy specimen showed four small cancerous lesions, three of which were EBER‐posltlve, and three EBER‐positive, minute, non‐cancerous dysplastic lesions. The three cancerous lesions were intramucosal cancer, with one having minimal submucosal invasion forming 8 lymphoeplthelioma‐like histology. All of these EBER‐posltlve cancerous and dysplastic lesions showed Intense CD8T‐lyrnphocytic Infiltration. There was no such findings in the EBV‐negative cancerous lesion. It was concluded that EBV infection may occur in the epitheilal cells of atrophic gastric mucosa, and progress to cancer with monoclonal expansion through the EBV‐positive dysplastic change. Cytotoxlc T‐lymphocytic reactions can occur even in the dysplastic lesions. Multifocal EBV infection in the gastric mucosa may occur and, if necessary, total gastrectomy Is recommended in such a case.
Primary renal angiosarcoma: A case report and review of the literature
Authors: Tsuda Nobuo , Chowdhury Paritosh Roy , Hayashi Tomayoshi , Anami Masanobu , Iseki Masachika , Koga Shigehiko , Matsuya Fukuzo , Kanetake Hiroshi , Saito Yutaka , Horita Yoshio
Published: December 2008

Primary renal angiosarcoma is very rare. To our knowledge, only 15 cases have been reported to date. A 77‐year‐old Japanese man with a unilateral kidney presented with massive hematuria followed by renal failure. A renal tumor was suspected and a left nephrectomy was performed. The histopathological diagnosis was angiosarcoma of the kidney. A hemorrhagic tumor measuring 10 × 5 cm and clotted blood was found in the modularly area. The atypical tumor cells had a sinusoidal and solid appearance, and showed Immunohistochemically positive reactions for some of the endothelial markers. The patient died about 21 months after the nephrectomy and the autopsy revealed massive metastases to the liver and retroperitoneum. One of the differential diagnoses of the case was anglomyolipoma, because the tumor cells were relatively bland in their histological appearance with entrapped fat cells in the pelvic area. Fifteen case reports with titles that included the term ‘hemangiosarcoma/anglosarcoma’, ‘hemangioendothelloma/endothelloma’ or ‘vascular sarcoma’ of the kidney were reviewed and compared to the present case.
‘Ovarian‐type’ stroma of pancreatic mucinous cystic tumor expresses smooth muscle phenotype
Authors: Fukushima Noriyoshi , Mukai Kiyoshi
Published: December 2008

‘Ovarian‐type’ stroma of nine mucinous cystic tumors (MCT) of the pancreas, six cystadenomas and three cystadenocarcinomas, were studied immunohistochemically. Most of the spindle cells of the ‘ovarian‐type’ stroma were positive for smooth muscle actin and desmin, but were negative for S‐100 cytochrome p450 19 and CD34. Similar stroma with smooth muscle differentiation has been described in hepatobillary MCT. Embryologic similarity between the pancreas and liver suggests a closely related origin of MCT In both organs.
Copper and iron‐induced oxidative damage in non‐tumor bearing LEC rats
Authors: Ma Yuxiang , Zhang Daxian , Kawabata Teruyuki , Kiriu Takahiro , Toyokuni Shinya , Uchida Koji , Okada Shigeru
Published: December 2008

The copper and Iron status in the liver of non‐tumor bearing Long‐Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely‐bound copper and iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA‐chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA‐chelatable free copper was also higher in LEC rats than In LEA rats (P<0.05). But for the free iron level there was no signiflcant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid‐reactive substances was higher In LEC rats than In LEA rats (P<0.01). The 4–hydroxy‐2–nonenal (HNE)‐modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect In the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor‐induction nor preneo‐plastic lesions in the experimental LEC rats were observed. Therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important translation metals In the body, may participate In the Induction of DNA damage and oncogenesls
Fas antigen expression and its relationship with apoptosis in transplanted kidney
Authors: Kato Shlgeo , Akasaka Yoshikiyo , Kawamura Sadao
Published: December 2008

A total of 244 human renal blopsy cases were examined under the following three categories of renal disease: (I) transplanted kidney (TK; 127 cases); (II) primary glomerular disease (GD; 88 cases); and (III) others (29 cases). In these cases, the immunohistochemical distribution of apoptosis‐related proteins (Fas antigen and bcl‐2 protein) was investigated. Despite no detection in normal kidney tissues, Fas antigen was highly expressed in the tubular epithellum, Indicating that Fas antigen expression was induced on the tubular epithelium in human renal disease. Furthermore, In TK Fas antigen expression was significantly frequent in acute rejection including acute rejection borderline (9/43 cases) and acute rejection stages I—III (10/28 cases), as compared with that in control cases (no rejeation. 1/32 cases). Fragmented DNA stalned with in situ nick end‐labeling was predominantly detected in the tubular epithelium in 6 of 48 cases (23 with transplanted kidney and 21 with glomerular disease). Characteristic nuclear apoptotic changes were detected In the tubular epithelium by light microscopy. These results indicate that apoptosis takes place mainly in the renal tubular epithelium. The present experimental study revealed that Fas mRNA transcripts were induced in human renal cell line by interteron‐γ. This suggests that in situ induction of Fas antigen in the tubular epithelium is mediated, at least in part, by cytokines in association with inflammatory lympho‐cytic infiltrates. it was also revealed that anti‐Fas monoclonal antibody induced apoptosis of the renal cell line through stimulation with interferon‐γ. Taken together, the results suggest that induced expresaion of Fas antigen on the tubular epithelium might play an important role in apoptosis under acute renal graft rejection.
Modulation of S‐100 genes response to growth conditions in human epithelial tumor cells
Authors: Matsumoto Takashi , Murao Shinichi , Kito Katsumi , Kihana Toshimasa , Matsuura Shumpei , Ueda Norifumi
Published: December 2008

Many new members of the S‐100 genes are known to be associated with cell differentiation, malignant transformation, and cell cycle. Of the S‐100 genes examined In the present study, calcyclin, calpactin I light chain and calvasculln were expressed In most human epithellal tumor cells, and their expression levels differed according to various growth conditions. Their transcribed levels differed depending on each cell line, but their expression patterns were similarly changed under growth‐modulatory conditions. Their messenger RNA levels increased parallel to the S phase population of cells, and decreased at G1/G2 phases. In contrast, this expression diminished in tumor cells under growth‐Inhibitory conditions, such as treatment with topolsomerase II inhibitor VP‐16 or phorbol 12‐myristate 13‐acetate.
Juxtaglomerular cell tumor of the kidney: Report of a non‐functioning variant
Authors: Endoh Yasushi , Motoyama Teiichi , Hayami Shinsuke , Kihara Itaru
Published: December 2008

A case of a juxtaglomerular cell tumor (JCT) in a 46‐year‐old man is reported. The tumor, 2.4 cm at its greatest dimension, was incidentally detected by ultrasonography. Although histological, immunohistochemical, and electron microscopic examinations revealed typical features of a JCT, the patient had no history of hypertension or hypokalemia. This is the first report of a non‐functioning JCT in the literature.
A new aspect of gastric metaplasia in Crohn's disease: Bidirectional (foveolar and pyloric) differentiation in so‐called ‘pyloric metaplasia’ in the ileum
Authors: Kushima Ryoli , Borchard Franz , Hattori Takanori
Published: December 2008

Wucus‐secreting cells found at the site of lieac ulceration in Crohn's disease have been described as ‘pyloric metaplasla’. Using mucin‐histochemical methods and Immunohistochemical stainings for KI‐67 antigen and foveolar‐type much (M1) of the stomach, the charecteristics of this type of metaplasia were studied in surgically resected lieac specimens from two Japanese patients with Crohn's disease. Not only pyloric‐type cells but also foveolar‐type cells were demonstrated; often displaying an organold growth of the normal stomach mucosa. Stem cells of the ileac crypt may differentiate potentially to intestinal‐, pyloric‐ and also to foveolar‐type cells. The term ‘pyloric metaplasia’ is not appropriate and ‘gastric metaplasia’ should be used when describing this type of metaplasia.
Small cell carcinoma arising from the outer urethral orifice: A case report examined by histologic, ultrastructural and immunohistochemical methods
Authors: Fukuda Takeaki , Kamishima Tomoko , Saito Takahisa , Itoh Seiki , Suzuki Toshimrtsu
Published: December 2008

A case of small cell carcinoma arising In the outer urethral orifice is presented. The resected tumor showed a proliferation of small round or fusiform neoplastic cells in the submucosa. Tumor cells were arranged in sheets or a trabecular manner and possessed markedly hyper‐chromatic nuclei with a high N: C ratlo, closely resembling small cell carcinoma of the lung. Characteristically, pagetoid lntraepithellal spreading could be identified. However, there was no evidence of in sku transitional cell carcinoma and adene or squamous cell carcinoma components anywhere. Ultrastructurally, each tumor cell contained only a few membrane‐bound cored granules measuring 60–100 nm, which were compatible with neurosecretory granules, and desmosomellke Intercellular attachments, but lacked aggregated microfilaments. By immunohistochemical examination, tumor cells were positive for eplthelial markers, such as cytokeratln and epithellal membrane antlgen, and neuron specific enolase, but negative for any other neuro‐endocrine markers. Extensive systemic examinatlon falled to show the primary site to be other than the outer urethral oritlce. These findings lndicate that the current tumor is a small cell carclnoma with neume‐ndocrine differentiation arising from the outer urethral orifice.
Detection of the Epstein‐Barr virus genome in cervical neoplasia is closely related to the degree of infiltrating lymphoid cells: A polymerase chain reaction and in situ hybridization approach
Authors: Shojl Yoko , Saegusa Makoto , Takano Yasuo , Hashimura Miki , Okayasu Isao
Published: December 2008

To cast light on the significance of Epstein‐Barr virus (EBV) infection In cervical tumorigenesie, 44 cervical lntraepithellal neoplasia (CIN) types I/II, and 70 CIN III lesions, 60 lnvasive squamous cell carcinomas (ISCC), and 20 normal cervical samples were Investigated by polymerase chain reaction (PCR) and RNA in situ hybridization (RISH) assays. The EBV genome was detected by PCR using primers targetlng the IR region in three (6.8%0) of the CIN I/II, 15 (21.4%) of the CIN III and 13 (21.7%) of the ISCC lesions, while using an EBER oligonucieotide probe RISH revealed positive signals in Infiltrating lymphocytes located In the cervical stroma, but not in dysplastic or tumor cells. There was a significant correlation between the presence of EBV DNA and the degree of lymphoid cell infiltratlon (P=0.0223). In contrast, none of the normal cervical samples that were without inflammation demonstrated any EBV infection. Thus, the results indicated that a positive result for EBV on PCR may be simply dependent on the amount of lymphocytes in cervical stroma, suggesting that this virus does not play a major role In the etiology of cervical neoplasia.
Reactivity of antibody YU‐311 in formalin‐fixed, paraffin‐embedded specimens of normal organs, non‐hematopoietic tumors, and mast cell tumors
Authors: Fukuda Takeaki , Kamishima Tomoko , Kakihara Toshio , Yamada Toshiyuki , Matsumoto Kazuhito , Uchiyama Makoto , Suzuki Toshimitsu
Published: December 2008

YU‐311 Is a monoclonal antibody that reacts with a human leukemia cell line resistant for cytoslne arabinoside and that Identifies a 92 kDa membrane protein. The reactivity of YU‐311 in normal organs, various non‐hematopoietic tumors and in mast cell tumors In formalin‐flxed, paraffinembedded specimens was examined using immunohlstochemlcal methods. in normal organs, YU‐311 reacted with fundic glands of the stomach, the Intercalated duct of the pancreas, the distal portion and the loop of Henle of renal tubules and tlssue mast cells. Benign neoplasms of various organs showed no immunoreactlon with YU‐311, except for mast cell tumors. Some types of malignant neoplasms were occasionally positive against YU‐311, suggesting neoplasms arising from or differentiating along normal YU‐311‐positive counterparts. Some other types of malignancies were rarely positive for YU‐311, although their normal counterparts showed no immunoreactlvity with YU‐311. None of the non‐epitheilal tumors reacted with YU‐311, except for one case of malignant melanoma. in contrast, normal tissue mast cells and their related tumors, such as urtlcarla pigmentosa or solitary mastocytoma, were constantly positive for YU‐311. None of the non‐hematopoietlc human tumor cell lines examined in the present study was reactlve with YU‐311. These findlngs indicate that YU‐311 is a good marker of some types of tumors and mast cell tumors and that an aberrant expression of YU‐311 rarely occurs.
Frequent Occurrence of hepatocytic apoptosis in acute rejection of the grafted rat liver
Authors: Hayashi Atsushi , Ito Hisao , Shomori Kouhei , Ohdan Hideki , Yano Kenji , Asahara Toshimasa
Published: December 2008

The present study was conducted to examine the hlstopathologlcal changes of rat liver grafts in the early post‐transplantation period. A total of 44 orthotoplc liver transplantations were performed using cuff techniques without anastomosis of the hepatic artery. They were divided into four groups: (1) group 1 (syngeneic, Lewis Lewis; n=10); (11) group 2 (aliogeneic, ACI — Lewis; n=20); (iii) group 3 (aliogeneic with immunosuppression, ACI —Lewis; n=12); and (iv) long‐survlvlng grafts (PVG — Lewis; n‐2). The histological findings were ciassified into four categories: (i) mild dilatation of Disse's spaces due to ischemia; (ii) bile duct proliferation; (iii) acute rejection; and (Iv) zonal necrosis. Blie duct proliferation occurred on day 6 in ail three groups and in one of the two long‐surviving grafts (120 days). Acute rejection occurred on day 3 and progressed in groups 2 and 3. Zonal necrosis developed in group 2 after day 6, while acute rejection subsided after day 4 In group 3 receiving 15‐deoxyspergualln. A few slngle cell deaths or acldophlllc bodies were varlably noted. Most of these cells showed slgnals by In s/tu nick end‐labellng In thelr nuclei, Implying the cells were undergoing apoptosls. The number of apoptotlc hepatocytes Increased as the progress and decreased wlth the regresslon of acuto reJectlon In group 3. Thus, the extont of hepatocytlc apoptosis may raRsct the megnltud. of scute rqoctbn. Mon frequent dlsttibutlon of apoptotlc hepatocytes In prrlportrl areas suggests that apoptosls may be Induced by a varbty of pethotoglcal stimull, Including the dinct cytotoxlc effact of lymphocytes, various cytokines and local circulrtory disturbances.
p53 protein overexpression and K‐rascodon 12 mutation in pancreatic ductal carcinoma: Correlation with histologic factors
Authors: Kasuya Kazuhiko , Watanabe Hidenobu , Nakasako Toshiaki , Ajioka Yoichi , Koyanagi Yasuhisa
Published: December 2008

The correlation of p53 protein overexpression and the K‐ras codon 12 mutatlon wlth histologlc type, grade of cytologic atypla, depth of lnvasion and other histologlc prognostic factors was studied In paraffin sectlons from 43 ductectatic‐and 70 solid‐type pancreatic ductal carcinomas. Overexpression of p53 was found in 23.3% (10143) of ductectatic carcinomas (17.2% of intraductal and 35.7% of lnvaslve carclnomas) and in 61.4% (43/70) of solid carcinomas. In ductectatic cancers, p53 overexpression was detected In 14.8% (4/27) of carcinomas wlth lowgrade atypla (CAL), 50.0% (5110) of carcinomas wlth high‐grade atypla (CAH) and in 16.7% (In) of mixed low‐ and hlgh‐grade cancers. In the last group, expression was restricted to an area of CAH. In solld cancers, p53 overexpression did not dlffer by histologic type or grade. Overexpresslon of p53 and K‐ras mutatlons did not correlate with histologlc prognostic factors (lymphatic, venous and perineural Invasion, and lymph node metastasls) in ductectatlc and solld cancers or depth of invasion of solld carclnomas. Our data suggest that p53 alteratlon occurs at an early intraductal stage of solld carcinoma, irrespectlve of cellular atypla, but Is low in ductectatic CAL and becomes hlgher In ductectatlc CAH. K‐ras mutatlon, present In a high percentage of tumors of all groups and not correlating with the factors above, showed no changes In frequency with tumor progression.
Tophaceous pseudogout of the temporomandibular joint: Report of a case
Authors: Kurihara Kenji , Mizusekl Kiyoshi , Saiki Tadahiko , Wakisaka Hiroyuki , Maruyama Shigeo , Sonobe Junya
Published: December 2008

An 85‐year‐oid man was found to have a calcified mass protrudlng from the Joint space of the right temporomandibular Joint (TMJ). Microscopically, the removed mass consisted of chondromyxold tissue with atypical chondrocytes, resembling a cartilaginous tumor. However, the chondromyxoid tissue contained abundant deposits of rod‐shaped to rhomboid crystals which proved to be calcium pyrophosphate dihydrate (CPPD) crystals. The review of the literature revealed that tophaceous pseudogout was the most common variant of CPPD deposltion dlsease Involving the TMJ.
Stromal reaction in cancer tissue: Pathophysiologic significance of the expression of matrix‐degrading enzymes in relation to matrix turnover and immune/inflammatory reactions
Authors: Ohtani Haruo
Published: December 2008

Cancers are characterized by invasive growth and distant metastasis. Cancer cells not only destroy the pre‐existing extracellular matrix, but cancer invasion per se usually induces new matrix formation by activation of stromal cells; that is, desmoplastic reaction. This process includes both matrix production and degradation; that Is, the remodeling process. The similarity between desmoplastic reactions in cancer stroma and the wound healing process has already been pointed out, and it has been well documented that matrix‐degrading processes are actively involved In the wound healing process. A recent study revealed that most matrix‐degrading enzymes, generally considered to be one of the main mechanisms of cancer invasion and metastasis, are originated from stromal cells. Based on these preconditions, the present review postulates that the abundant expression of matrix‐degrading enzymes by fibroblasts, coupled with the abundant expression of type I procollagen, is involved in the matrix remodeling processes occurring in cancer stroma; that is, the mechanism similar to the wound healing process. Next, macrophages distributed along the invasive margin are known to express matrix‐degrading enzymes/factors. Data from past studies of colon carcinoma indicate that the tissue expression of matrix metalloproteinase‐9 and urokinase‐type plas‐mlnogen activator receptor Is inversely associated with simultaneous liver metastasis and infiltrating growth pattern. Previous clinicopathologic data have indicated that immune/Inflammatory cells are one of the factors for a favorable prognosis. This suggests that the expression of matrix‐degrading enzymes/factors by these host cells may be involved in host immune/inflammatory reactions, and that the net function of these cells can be defensive towards the host. Data from past studies of colon carcinoma on the expression of the intercellular adhesion molecule‐1 suggest that the interaction between macrophages, lymphocytes, and the phenotypes of venules distributed along the Invasive margin, further support the pro‐inflammatory milieu there. Therefore, the matrix degradation process in cancer tissue is multifunctional: besides the Involvement in cancer invasion and metastasis, the matrix degradation process is also involved in the tissue remodeling process and in the immune/inflammatory reaction occurring in the stroma.
Expression of MUG1 glycoprotein in plasma cells, follicular dendritic cells, myofibroblasts and perineurial cells: lmmunohistochemical analysis using three monoclonal antibodies
Authors: Kamoshida Shingo , Tsutsumi Yutaka
Published: December 2008

Normal and mallgnant plasma cells (PC), follicular dendritic cells (FDC), myoflbroblasts (MFB) and perineurial cells (PNC) were Investigated for the expression of YUC‐1 glycoprotein (MUC‐1 gp) by immunohistochemical and immunoelectron microscopic techniques uslng monocional antibodies E29, 115D8, DF3 and a combination of the three. MUG1 glycoprotein‐positive PC detected by the combined antibodies were frequently seen in a variety of pathological lesions tested, including chronic cervicitls, chronic syno‐vitis, Hodgkin's disease, allergic rhlnitis and sinusitis, tuberculous lymphadenitis, foreign body granuloma, multiple myeloma, and chronic tonsillitis. In the lesions containing MUC‐1gp‐positive PC, the infiltration of immunoglobulin (lg) E PC and/or IgE‐bound mast cells was significantly increased, but MUC‐1gp‐positive PC did not contain any specific immunoglobulin heavy or light chains. The findings suggest that the expression of MUC‐1gp In PC, although not restrlcted to IgE‐class cells, may be Induced in an allergic status. Plasma cells and PNC mainly reacted with the antibodies E29 and 115D8, while FDC and MFB were principally reactive wlth the antibody DF3. In some cases of multiple myeloma, the neoplastic PC were predominantly immunoreactive with DF3. The results indicate: (i) the epitopic variability of MUC1gp molecules expressed on the non‐epithelial cells; and (ii) the epitoplc alterations during malignant transformation. It should also be noted that the expression of MUG‐1 gp in the nonepithellal cells represents a pitfall in histopathological diagnosis.
Nodular hidradenoma of the breast: Report of two cases with literature review
Authors: Domoto Hideharu , Terahata Shintaro , Sato Kimiya , Tamai Seiichi
Published: December 2008

Two cases of nodular hidradenoma of the breast with possibly different origins are reported. Case 1 is of a 58 year‐old female wlth a breast mass in the left, outer lower‐quadrant. A histogenetical origin in the skin adnexal glands was suspected due to its superficial location and immuno‐histochemical findlngs. Case 2 is of a 44‐yearold male with a subareolar nodule and nipple discharge. Histological examlnation demonstrated that the tumor was located deep in the breast tissue, was surrounded by dilated mammary ducts and exhibited intraductal extenslons, which are all features mlmicking those of breast cancer. Immunohlsto‐chemical positivity against gross cystic disease fluid protein‐15 was weakly Identified and negativity for endo‐plasrnic reticulum was observed. This case can be interpreted as arising In the mammary ducts. It is well known that various kinds of skin adnexal tumors arise in the breast tissue; however, nodular hidradenoma of the breast is still a rare benign neoplasm. Cllnically, nodular hidradenoma of the breast tends to occur in the nipple or subareolar region of the female breast. It should be kept in mind that nodular hidradenoma may occur in mammary ducts and it should be included when differential diagnoses are made of subare olar breast tumors.
Clinicopathological study of severe chronic active Epstein‐Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome
Authors: Ohshima Koichi , Suzumiya Junji , Sugihara Midori , Nagafuchi Seiho , Ohga Shouichi , Kikuchi Masahiro
Published: December 2008

Chronlc active Epstein‐Barr virus (CAEBV) infection has been prevlously reported to be sometimes associated with an aggresslve clinical course. However, the role of EBV in the CAEBV Is not well clarifled. A retrospective study was performed on nine adult and five child patients (eight males and six females). Histologlcally, at first admission, the presence of neoplastic lesions could not be confirmed. The lymph nodes In half of all cases revealed paracortical hyperplasla with transformed lymphocytes (hyperplastic type). Half of the cases showed nonsuppuratlve necrosis and an Increased number of histiocytes with phagocytosis (histiocytic type). Activated histiocytes with lymphokine positivity were frequently detected in the histiocytic type. In the phenotypical study, 10 of the examined 11 cases showed Increased numbers of natural killer (NK) cells and/or CD8 positive T lymphocytes. In situ hybridization (ISH) showed EBV‐Infected lymphoid cells, but the number of EBV‐infected cells varied. Double‐labeling irnmunochemistryASH demonstrated EBV‐infected T cells, including NK cells, but not B cells. In addition, three cases showed a monoclonal dissemination of EBV terminal repetitive sequence (TR), and two cases showed oligoclonal dissemination. From those findings, monoclonal, oligoclonal and polyclonal populations of EBV‐infected T or NK cells were considered to be present in CAEBV states. During the clinical course, 12 of the 14 cases died within 5 years. Six cases died from EBV‐associated hematopoietic tumors (histiocytlc tumor, T cell lymphoma, B cell lymphoma, plasmacytoma, and NK cell leukemia); one from non‐EBV‐associated acute myeloge‐nous leukemia, and five due to hemophagocytic syndrome. The examined EBV‐associated hematopoietic tumors showed monoclonal EBV terminal repetitive sequences. There is a possibility that the monoclonal dissemination of EBV‐infected cells develops from oligoclonal or polyclonal EBV‐infected cells. And active histlocytes with lymphokine positivity were frequently detected In the cases with histologically histiocytic type. These findings seem to be related with the causes of death due to hemophagocytic syndrome.
Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin‐induced pulmonary fibrosis
Authors: Yaguchi Takamoto , Fukuda Yuh , Ishizaki Masamlchi , Yamanaka Nobuaki
Published: December 2008

The role of various matrix metalloproteinases (MMP) and tissue Inhibitor of metalloprotelnases‐2 (TIMP‐2), and the gelatholytic activities of MMP involved in the process of bleomycin‐induced pulmonary fibrosis in rabbits were Investigated. Male Japanese white rabbits were intubated with tracheal tubes under anesthesia, and bleomycin hydrochloride in sterile saline or only sterile saline was administered through the tracheal tubes. The animals were killed 1, 3, 7, 14 and 28 days after the administration of bleomycln (n = 3) or saline (n = 2). Light microscopic lmmunohistochemlstry for MMP‐1 (interstitial collagenase), MMPP (gelatinase A), MMP‐9 (gelatinase B) and TIMP‐2 was performed. The gelatinolytic activities of lung tissue homogenates were studied by gelatin zymography. In the early stages, the gelatholytic activity of MMP‐9 was predominant. MYP‐9 localized in the infiltrating neutrophils, macrophages, bronchial and bronchiolar epithelial cells. The alveolar epithelial basement membrane was frequently disrupted in the early stages, where MMP‐9 possibly contributed to the disruption. In the late stages, the gelatinolytic activities of the latent and active forms of MMP‐2 were predominant, and MMPP localized in the regenerated alveolar epithelial cells in addition to the bronchial epithelial cells. MMP‐2, especially its active form, possibly plays a role in alveolar epithelial cell regeneration. The localization of MMP‐1 was similar to that of MMP‐9. TIMP‐2 localized in the epithelial cells and in some fibroblasts in fibro tic lesions. TIMP‐2 possibly plays a role in extracellular matrix deposition in balance with MMP.
Retroperitoneal leiomyosarcoma of a male centenarian
Authors: Yokoo Hideaki , Nakazato Yoichi , Fukuyama Hiroshi , Miyakhi Osamu , Sato Tsuneko
Published: December 2008

An autopsy case of retroperitoneal leiomyosarcoma of a centenarial male is described. He complained of abdominal pain In his left side 1 month before his death. Ultrasonog‐raphy and computed tomography revealed a large mass in the left abdominal cavity. At autopsy, a circumscribed mass, 15 cm in diameter, was found in the left‐upper abdominal cavity, and seemed to be derived from the retroperitoneum in an exophytic manner. Histologically, spindle cells with slight eosinophillc cytoplasm and blunt‐ended nuclei showed interwoven fascicular growth, and mitotic figures were easlly encountered. Immunohlstochemically, the tumor cells were labeled by α‐smooth muscle actln and vimentln. To our knowledge, this case of leiomyosarcoma has presented in the oldest patient ever reported. The rarity of soft tissue sarcomas in the extremely elderly is also discussed.
Secretory carcinoma of the breast in a 51‐year‐old male
Authors: Kameyama Kaori , Mukai Makio , Iri Hisami , Kuramochi Shigeru , Yamazaki Kazuto , Ikeda Yoshifumi , Hata Jun‐ichi
Published: December 2008

Approximately 100 female secretory Carcinoma cases have been reported. Although thls tumor was Initially termed juvenile carcinoma as the patients were all children and adolescent females, subsequent reports demonstrated that it occurs in females of all ages. Moreover, to date, only five males with this tumor have been reported. As with the initial female secretory carcinoma cases, all five were children or young adutts. A very rare case of non‐invasive secretory carcinoma of the breast arising in a 51‐year‐old Japanese male Is described. He presented with a lump in his left breast. The surgically resected tumor was a typical secretory carcinoma histologically, except that there was no Infiltration of the surrounding stroma, and was composed of tumor cells with vacuolated cytoplasm that contained secretory materials. This case, the first recorded secretory carcinoma of the breast in a middle‐aged male, demonstrates that this tumor may also arise in mature males, as is the case in females. Physicians should not rule out the possibility of a secretory carcinoma of the breast regardless of patient age and gender.
Vascular endothelial growth factor and neovascularization in astrocytic tumors
Authors: Takekawa Yoshinori , Sawada Tatsuo
Published: December 2008

It has been widely recognized that the vascular structure is an important factor when making a histopathological diagnosis and assessing the malignancy potential, especially of astrocytic tumors. The vascular endothelial growth factor (VEGF), which is thought to be regulated by the p53 gene, is a regulation factor for tumor neovascularization. The relationship between VEGF distribution and neovasculature was studied in 42 cases of astrocytic tumors (grades 1–4), which were obtained from surgical material, and the St Anne‐Mayo grading system was applied. The relationship between the labeling indices (LI) of VEGF and LI of p53 protein in tumor cells was also studied using immunohistochemistry. The VEGF LI in high‐grade malignancy potential tumors, such as grade 3 and grade 4 tumors, was significantly higher than those that were low grade. In grade 4 tumors, a significant correlation between the VEGF LI and the proliferation indices of endothelial cells of neovasculatures was observed. No significant correlation was noted between p53 LI and VEGF LI, as well as p53 LI and histopathological grade. In astrocytic tumors, expression of VEGF may be correlated to tumor neovascularization, and can be considered as an indicator of malignancy potential in astrocytic tumors.
Prediction of efficacy of interferon treatment of chronic hepatitis C by multivariate analysis and a new classification
Authors: Kim Soo Ryang , Hayashi Yoshitake , Yoon Seitetsu , Taniguchi Miyuki , Yang Moo Kwan , Kim Ke Ih , Kim Myung Mi , Saeki Keizo , Nukata Isao , Imoto Susumu
Published: December 2008

One hundred and fifteen patients with chronic hepatitis C were administered interferon (IFN) and classed into two groups: (i) complete responders (CR), HCV‐RNA continuously negative 1 year after treatment; and (ii) non‐responders (NR), positive 1 year after treatment. Multivariate analysis comprised eight variables: age, sex, transfusion history, alanine aminotransferase level, viral genotype, level of viremia, type of IFN, and total amount of IFN. The HCV‐RNA level was correlated with complete response (P = 0.0175). Liver biopsy specimens were classified into four grades and stages according to the measure of severity and the extent of fibrosis, respectively. There was no correlation between the efficacy rate and grading. However, in staging there was a difference in the efficacy of IFN between stages 1 or 2, and stage 3 (0.05<P<0.1 and 0.01 <P<0.025, respectively). Of the CR patients, 0% (0/5) were at stage 0 (no fibrosis); 27.5% (22/80) at stage 1 (mild); 42.9% (6/14) at stage 2 (moderate); and 6.3% (1/16) at stage 3 (severe fibrosis). Thus the new classification would be useful in predicting roughly the efficacy of IFN.
Multiple organ failure associated with extensive metastatic calcification in a patient with an intermediate state of human T lymphotropic virus type I (HTLV‐I) infection: Report of an autopsy case
Authors: KUMAMOTO HIRBYUKI , ICHINOHASAMA RYO , SAWAI TAKASHI , NAGANUMA HIROSHI , FURUKAWA YOTARO , AKIU NAOKI , KANO MAKI , OOYA KIYOSHI
Published: December 2008

A patient with an intermediate state of human T lymphotropic virus type I (WLV‐I) infection and in whom autopsy showed multiple organ failure (MOP associated with extensive metastatic calcification in systemic organs is described. A 56‐year‐old man presented with signs and symptoms of advanced cardiac insufficiency, respiratory disturbance and renal failure. Serologically, the anti‐human T lymphotropic virus type I (HTLV‐I) antibody tier and the levels of both calcium and parathyroid hormonerelated peptide (PTHrP) were dlstinctly elevated. These data suggested a diagnosis of adult T cell lymphoma/leukemia (ATLL). However, examination of a peripheral blood sample revealed only a few atypical lymphoid cells (3%) associated with mild leukocytosis (white blood cell count, 13.7 × 103/mm3). Lymph node swelling was systemic but mild, with some nodes up to 10 mm In diameter. The patient died of MOF. Adult T cell leukemla/lymphoma was unable to be diagnosed definitively because of the short duration of laboratory abnormalities and because of the discrepancy between the laboratory data and the magnitude of lymphoprollferation in both the lymph nodes and peripheral blood. At autopsy, the most conspicuous finding was extensive metastatic calcification in the multiple organs, including the heart, lungs, kidneys, tongue, liver, pancreas, spleen and systemic arterial walls. Very small numbers of medium‐sized atypical lymphoid cells admixed with small reactive lymphocytes were Identified in multiple organs, with no evidence of massive Infiltration. Molecular analyses could not detect monoclonal Integratlon of HTLV‐I provirus DNA or monoclonality of T cell lineage cells. Parathyroid hormone‐related peptide was demonstrated In the cytoplasm of the atypical lymphoid cells on lmmunohls‐tochemical examination. The bone trabeculae generally showed distinct evidence of resorption associated with marked proliferation of osteoclasts. These findings suggested that the hypercalcemia in the present case was categorized as humoral hypercalcemia of malignancy rather than local osteolytic hypercalcemia.
Gastric low‐grade mucosa‐associated lymphoid tissue lymphomas: Their histogenesis and high‐grade transformation
Authors: Yoshino Tadashi , Akagi Tadaatsu
Published: December 2008

Gastric low‐grade mucosa‐associated lymphoid tissue (MALT) lymphoma is a unique disease. A vast majority of lymphoma cells are centrocyte‐like cells or resemble monocytold B cells, and occasionally show plasmacytic differentiation. Immunophenotypical and immunogeno‐typical examinations have indicated that they are in the differentiation stage of memory B cells, whose normal counterparts are marginal zone lymphocytes or monocytoid B cells In the lymphoid tissues. It arises from chronic gastritis closely associated with Helicobacter pylori (H. pylori) infection. Mucosa‐associated lymphoid tissue lymphomas of other organs are also based on acquired MALT associated with chronic inflammation or autoimmune diseases. Interestingly, the majority of gastric low‐grade MALT lymphomas regress by the eradication of H. pylori. The lymphoma cells, however, are not derived from B cells reacting with H. pylori itself but from autoreactive B cells. Although the mechanism of their oncogenesis has not been clarified, previous data suggest that autoreactive B cells proliferate in response to H. pylori‐specific T cells, presumably with some cytoklnes. The genetic Instability of such B cells then induces chromosomal abnormalities including trisomy 3 and/or other genetic changes. These B cells have the ability of autonomic proliferation and, even so, they might be sensitive to T cell stimuli. Low‐grade gastric lymphomas occasionally progress to high‐grade malignancy. The high‐grade component of MALT lymphomas are composed of large‐sized lymphoma cells that are morphologically indistinguishable from nodal large B cell lymphomas. This high‐grade transformation is associated with p53 abnormalities or Bcl‐6 overexpresslon. Gastric MALT lymphoma may provide a useful model in understanding multistep lymphomagenesls.
Systemic mast cell disease with splenic infarction: A case report
Authors: Maruyama Hiroshi , Sugihara Seiichi , Ishihara Kyoko , Sada Kazuo , Tsutsumi Masahiro , Tsujiuchi Toshifumi , Nakae Dai , Konishi Yoichi
Published: December 2008

An autopsy case of systemic mast cell disease (SMCD) without primary skin lesions in a 57‐year‐old Japanese male Is described. Initially the patient was suspected of having liver cirrhosis or malignant lymphoma because of hepatomegaly and lymph node enlargement on admission. However, a lymph node biopsy and bone marrow aspiration conducted on his third admission indicated a SMCD because of the existence of metachromatic cell aggregates stained with toluidine blue. At autopsy, the diagnosis was confirmed because the proliferating cells were histochemlcally proven to be mast cells by naphthol AS.D chloroacetate esterase, Glemsa and alcian blue, in addition to toluidine blue staining. The intra‐abdominal and retroperitoneal lymph nodes were replaced by mast cell aggregates, which caused the splenic infarction and bilateral hydronephrosis, with infiltration of mast cells into the spleen and kidneys also being apparent. Mast cell infiltration was similarly found in the bone marrow, liver, lleum and ascending colon. Immunohistochemically, the mast cells were positive for antibodies of α1‐anti‐chymotrypsin, CD45 (LCA), CD43 (MT‐1), CD45R (MB‐1) and the oncoprotein c‐kit, Electron microscopic examination using formalin‐fixed tissue gave supportive evidence of a mast cell origin for the lesions.
A case report of renal cell tumor in a 45‐year‐old female mimicking lower portion nephrogenesis
Authors: He Qun , Ohaki Yoshiharu , Mori Osamu , Asano Goro , Tuboi Narumi
Published: December 2008

This report describes a renal tumor with an unusual histology In a 45‐year‐old woman. The tumor was white in color, different from usual renal cell carcinoma, and mainly consisted of variously shaped tubules formed by flat or cuboid cells within marked edematous stroma. Elaborated branching or tubules arranged In a papillary pattern with focal spindle‐shaped cell proliferation were characteristic features. Immunohistochemical staining expressed diffusely positive for vlmentin and S‐100 protein, partially positive for cytokeratin and epithelial membrane antigen and negative for Leu‐M1, Leu‐7, CD34 and markers for muscle cells. Ultrastructural studies of the tumor cells showed adenocarcinoma‐IIke characteristics. According to these histological, Immunohistochemlcal and electron microscopy findings, it is suggested that this tumor be designated as unclassified renal cell carcinoma with histology mimicking lower‐nephron nephrogenesis.
Ovarian mixed germ cell tumor composed of dysgerminoma, endodermal sinus tumor, choriocarcinoma and mature teratoma in a 44‐year‐old woman: Case report and literature review
Authors: AKAHIRA JUN‐ICHI , LTO KIYOSHI , KOSUGE SHYUICHI , KONNO RYO , SATE SHINJL , YAJIRNA AKIRA , SASANO HIRONOBU
Published: December 2008

A case of ovarian mixed germ cell tumor In a 44‐year‐old woman was examined. The tumor was well circumscribed, measured 15 times 11 times 10cm and appeared solid and partly cystic on the cut surface. Light microscopic examinations revealed that the tumor was composed of four different neoplastic germ cell elements, Intermingled with each other. They are: (i) choriocarcinoma, immunohistochemically positive for human placental lactogen (hPL) and human chorionic gonadotropin (hCG); (ii) dysgerminoma, positive for placental alkaline phosphatase; (iii) endodermal sinus tumor positive for α‐fetoproteln (AFP); and (lv) mature teratoma. Among these histological types, dysgermlnoma occupied more than 50% of the neoplasm. The patient was diagnosed as a stage la ovarian mixed germ cell tumor and was subsequently treated with chemotherapy. A second‐look laparotomy after completion of chemotherapy revealed no residual tumors in the abdomen and the patient Is alive and well 15 months after operation. This Is the fourth reported case of ovarian mixed germ cell tumor arising In patients over 40 years old.
Expression of vascular endothelial growth factor in human gastric carcinomas
Authors: Yamamoto Soichiro , Yasui Wataru , Kitadai Yasuhiko , Yokozaki Hiroshi , Haruma Ken , Kajiyama Goro , Tahara Eiichi
Published: December 2008

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a secreted protein which may play a pivotal role in tumor‐associated microvascular angiogenesis and hyperpermeability. The expression of mRNA for VEGF was examined in eight gastric carcinoma cell lines and 30 gastric carcinoma tissues as well as corresponding normal mucosa. All the cell lines expressed VEGF mRNA at various levels that correlated well with the amounts of VEGF secreted into the condition medium. The expression of VEGF mRNA by TMK‐1 cells was increased by the treatment of epidermal growth factor (EGF) or interleukin‐1α (IL‐1α), whereas it was decreased by the treatment of interferon‐β (IFN‐β). In gastric carcinoma tissues, the level of VEGF mRNA in primary tumors was higher than that in the corresponding normal mucosas in six (46%) of 13 well‐differentiated adenocarcinomas and in two (12%) of 17 poorly differentiated adenocarcinomas, respectively. Vessel counts in well‐differentiated adenocarcinomas had a tendency to be higher than those in poorly differentiated adenocarcinomas. In well‐differentiated adenocarcinomas, the levels of VEGF mRNA expression tended to be higher in carcinomas of advanced stage than in early stage carcinomas. Both in situ mRNA hybridization and immunohistochemistry demonstrated the presence of VEGF expression within the tumor cells. These results suggest that VEGF may confer angiogenesis and progression of human gastric carcinomas, especially of the well‐differentiated type.
Proportion of blasts with a clear halo around nucleoli at the end of induction therapy of acute myeloid leukemia correlates with achievement of complete remission, remission duration and relapse
Authors: Emura Iwao , Chou Takaaki , Ishiguro Takurou , Kakihara Toshio , Naito Makoto , Yoshizawa Hirohisa , Arakawa Masaaki
Published: December 2008

Bone marrow aspirates from 60 patients with acute myeloid leukemia (AML) were investigated using 95% ethanol flxation Papanlcolaou stained preparations. The blasts were grouped Into those with a clear halo around nucleoli (BCHN) and those without a clear halo. The patients were classified Into three groups according to the degree of persistent BCHN at the end of induction therapy: group 1, no BCHN; group 2, less than 1% BCHN; and group 3, 1% or more BCHN. All patients In groups 1 (17 cases) and 2 (12 cases), and 12 of 31 cases in group 3 achieved complete remission (CR). Of 17 patients in group 1, two underwent bone marrow transplantation and two died from infection. Of the 37 patients who achieved CR, relapse was observed in two of 13 patients in group 1, and in all patients in groups 2 and 3. As to the patients treated with N4‐behenoyl‐1–β‐d‐arabinofuranosyl‐cytosine + daunorubicin + 6‐mercaptop‐urine + prednisolone (BHAC‐DMP) protocol, the percentages and number of BCHN at the diagnosis of AML In group 1 were significantly lower than those of groups 2 and 3. The percentage and number of BCHN at the diagnosis of AML were significant factors for the achievement of CR and for the prediction of long‐term outcome. The reduction of BCHN to less than 1% at the end of Induction therapy is a good indicator for the achievement of CR, and the disappearance of BCHN is a useful target for a long‐lasting first CR; conversely, the persistence of BCHN is a major adverse factor for relapse.
GIiosarcoma: An immunohistochemical, uItrastructural and fluorescence in situ hybridization study
Authors: Horiguchi Hidehisa , Hirose Takanori , Kannuki Seiji , Nagahiro Shinji , Sano Toshiaki
Published: December 2008

Three cases of primaly gliosarcoma (GS) were studied by immunohistochemlcal, ultrastructural and fluorescence in situ hybridization (FISH) methods. All tumors occurred in the supratentorial regions of the body. No patient had a prior history of irradiation to the brain. All patients died of tumor within 1 year, and autopsies were performed in two cases. Microscopically, each of the three tumors showed a mixture of glioblastoma (GBM) and a sarcomatous component (SC), which resembled flbrosarcoma with various histological features. Numerous collagen and reticulin fibers were seen in the SC of all tumors. Glial fibrillaty acidic protein (GFAP) was immunoreactive only in the gliomatous component (GC). Factor VIII‐related antigen was negative except for endothelial cells. One tumor exhibited α‐smooth muscle actin positivity in the SC. Expression of MIB‐I and p53 protein was demonstrated in both components for all tumors. Labeling indices (LI) for MIB‐1 ranged from 7.7 to 36.1%, and LI for p53 protein ranged from 2.9 to 57.0%. Ultrastructurally, astrocytic cells were characterized by a polygonal configuration with many cytoplasmic projections and occasional filaments. Spindle‐shaped fibroblasts in the SC contained well‐developed rough endoplasmlc reticulum. Fluorescence in situ hybridization (FISH) performed on fresh materials or paraffin‐embedded tissue demonstrated single signals for chromosome 10 in 40.6–68.37% of cells and for chromosome 17 in 37.948.6% of cells. Two tumors were regarded as containing losses of both chromosomes 10 and 17, while the third showed a substantial loss only of chromosome 10. As similar aberrations have been reported in GBM, these chromosomal abnormalities suggest a common pathogenesis in GS and GBM.