bluuebunny/crossref_metadata_2025 huggingface dataset:
Intracranial meningioma masquerading as a primary pleuropulmonary tumor
Authors: Hishima Tsunekazu , Fukayama Masashi , Funata Nobuaki , Mochizuki Makoto , Hayashi Yukiko , Koike Morio , Ikeda Takaaki
Published: December 2008

Extracranial metastasis was found in an intracranial meningioma with low proliferative potential before the detection of the primary tumor. Pleuropulmonary tumors were incidentally detected on chest X‐ray in an asymptomatic 25 year old female. Excised tumors of the right pleura and lung showed histological features similar to meningotheliomatous meningioma, which led to the discovery and excision of the intracranial tumor. Both tumors showed the same histologic pattern: meningotheliomatous meningioma with low mitotic activity. The proliferative component, determined by the monoclonal antibody Ki‐67, was further evaluated in the primary tumor and the metastases of the present case, as well as in 12 other intracranial menin‐giomas. Ki‐67 positive ratios at the primary and metastatic sites of the present case were 1.2 and 1.1%, respectively, which is as low as other benign meningiomas, and this suggests that factors other than the proliferative potential is responsible for extracranial metastasis of meningioma.
p53 Mutation in carcinomas arising in ovarian cystic teratomas
Authors: Fujii Takeshi , Oguni Sachiko , Kikuchi Midori , Kanai Nobuyuki , Saito Ken
Published: December 2008

Carcinomas arising in mature cystic teratomas of the ovaries from nine women were examined for the presence of p53 mutations. The nine tumors comprised six squamous cell carcinomas, one squamous cell carcinoma in situ, one undifferentiated small cell carcinoma, and one muco‐epidermoid carcinoma. Abnormal nuclear accumulation of the p53 protein was obsenred in four of the tumors. Genomic DNA was extracted from formalin‐fixed, paraffin‐embedded tissue blocks and subjected to polymerase chain reaction (PCR) for specific amplification of the p53 gene exons 5–8, followed by direct chemiluminescence sequencing analysis. A frameshift mutation in exon 8 (codon 278, CCT > del T; stop at codon 344) was detected in one poorly differentiated squamous cell carcinoma. The samples were also evaluated for the possible association of ‘benign’ and ‘malignant’ types of human papillomavirus (HPV) by PCR using universal primer sets. None of the samples contained detectable HPV genome. These data suggest that p53 mutations are relatively uncommon in secondary carcinomas developing in ovarian. dermoid cysts, although the number of samples studied was admittedly small.
Duct‐acinar‐islet cell tumor of the pancreas
Authors: Okada Yoshikatsu , Mori Hiroshi , Tsutsumi Akira
Published: December 2008

A case of a rare pancreatic tumor, duct‐acinar‐islet cell tumor is presented. The tumor was incidentally found in the pancreatic body on computed tomography of a 21 year old male suffering from mumps. It was well demarcated from surrounding pancreas, and spherical in shape, measured 2.5 cm in diameter. Histologic and immunohistochemical examinations showed the tumor to consist of three distinct cell populations: duct, acinar and islet cells. Small cell nests consisting of these cellular components, either solely of one cell type or mixed of the three cell types, were separated by broad desmoplastic stroma. Islet (endocrine) cells, which were most predominant, were arranged in a tra‐becular pattern or small cell nests. Most of them were positive for glucagon, and a few cells expressed insulin, somatostatin, serotonin or pancreatic polypeptide. These cells were distributed randomly within the cell nests. Ducts, some of which contained goblet cells, were found among the endocrine cell nests. Duct‐islet complexes were also observed. The acinar cells were the least conspicuous component. They expressed pancreatic α‐amylase. An electron microscopic examination revealed duct cells with intercellular attachments and interdigitations, endocrine cells containing secretory granules, and acinar cells with zymogen granules. No definite evidence suggesting malignancy could be obtained.
CD68+ Reactive histiocytosis complicating early gastric cancer
Authors: Ogawa Yukari , Inada Ken‐ichi , Tsutsumi Yutaka
Published: December 2008

A peculiar form of reactive, non‐granulomatous proliferation of CD68+ histiocytes was demonstrated, for the first time, in the submucosal layer just beneath the IIa‐type early gastric adenocarcinoma that focally invaded submucosal lymphatics. The histiocytic cells possessed plump eosino‐philic and often foamy cytoplasm and eccentric small nuclei with apparent nucleoli. They contained periodic acid‐Schiff‐reactive granules, and were further immunoreactive for lysoryme and α1‐antttrypsin. The infiltration was ill‐defined, and partly involved the tunica muscularis mucosae and the proper muscle layer. Markers of epithelial cells, Langerhans' histiocytes, smooth muscle cells and myofibroblasts were all negative.
Functional nerve growth factor receptor in von Recklinghausen neurofibromatosis: An immunocytochemical and short‐term culture study
Authors: Hoshi Nobuo , Yamaki Toshifumi , Hiraki Hiroyuki , Natsume Toshiaki , Saitoh Atsuko , Watanabe Kazuo , Suzuki Toshimitsu
Published: December 2008

Immunocytochemistry reveals 75kDa low affinity type nerve growth factor receptor (NGFR) on the cell membrane of human neurofibroma cells of von Recklinghausen disease in vivo and in vitro. NGF‐immunoreactivity is detected in the primary and cultured tumor cells. Growth augmentation of cultured neurofibroma cells by exogenous NGF is also confirmed. Phosphotyrosine‐immunoreactivity is demonstrated by immunocytochemistry in the in vivo and in vitro neurofibroma cells suggesting possible phospho‐rylation of tyrosine residue in the NGFR or a cellular protein downstream of signal transduction through the ligand receptor system.

These results indicate human neurofibroma cells possess functional NGFR and the growth is potentiated through the NGF‐NGFR system in the paracrine and/or autocrine fashion.
Expression of bone morphogenetic proteins in human osteogenic and epithelial tumor cells
Authors: Ogose Akira , Motoyama Teiichi , Hotta Tetsuo , Watanabe Hidenobu
Published: December 2008

In addition to osteosarcomas some epithelial tumors also show bone induction, which is supposedly due to bone morphogenetic proteins (BMPs). However, the types of BMPs expressed in different kinds of tumors have not been studied extensively. In this study five human osteosarcoma and six human carcinoma cell lines were examined to investigate the bone induction and BMP mRNA expression. The cultured cells were transplanted in the subcutaneous tissue of athymic nude mice with or without diffusion chambers. Reverse transcription‐polymerase chain reaction (RT‐PCR) was used for the detection of BMP mRNAs. All osteosarcoma cell lines expressing all BMPs (BMP‐1 to 7) examined, successfully formed bone or osteoid tissue irrespective of the use of a diffusion chamber. Bone formation was induced by diffusion chamber in an osteosarcoma cell line OST and a gastric adenocarcinoma cell line MKN45. OST cells lacked BMP‐3 and 7, and MKN45 cells lacked BMP‐3, 5 and 6. Our data suggest that BMP‐3, 5, 6 and 7 are not always essential for bone induction in tumor cells.
The immunophenotype of perivascular cells in the human brain
Authors: Sasaki Atsushi , Nakazato Yoichi , Ogawa Akira , Sugihara Shiro
Published: December 2008

The immunophenotype of perivascular cells (PC) in temporal lobe tissues obtained at autopsy in 48 patients (aged 41–88 years) was characterized using light and electron microscopic immunocytochemistry with a variety of antibodies. In all cases studied, PC bearing CD11 c (Ki‐M1 P) and CD68 (KP1) were distributed throughout the temporal cortex. In addition to Ki‐M1P and KP1, the monoclonal antibodies against major histocompatibility complex (MHC) class II antigen (Ag) (LN‐3, CR3.43), anti‐leucocyte common antigen (LCA), LN‐5, Mac 387 were all found in PC with variable immunoreactivity. In contrast, LN‐1 and OPD4 were not found in PC, although the former showed nearly constant staining of resting microglia. Semiquantitative analysis disclosed differences in the numbers of cells labeled with the markers in the 21 normal brains (KI‐M1P > KP1 » LCA, LN‐3, LN‐5 » Mac 387). Ultrastructurally, immunoreactivity for Ki‐M1P, KP1, and LN‐3 was observed in PC with cytoplasm containing dense lysosomal bodies. In brains from patients with Alzheimer's type dementia, PC were seen in the wall of β‐amyloid protein‐positive small vessels. However, there was no definite alteration of anti‐genicity in PC from AD brains compared with those from normal brains. The immunophenotype of PC was similar to that of macrophages, which were observed in the perivascular spaces and the leptomeninges in some normal and diseased brains. In contrast with PC, however, macrophages showed high incidence of labeling for some mac‐rophage markers LN‐5 and Mac 387. These findings demonstrate that PC may be a normal constituent of the adult human brain with a variable expression of monocyte/ macrophages markers and MHC class II Ag and that PC could be distinguished from resting microglia by their morphology and by their immunophenotype.
Biphasic intra‐abdominal desmoplastic small cell tumor in a patient with proximal spinal muscular atrophy
Authors: Motoyama Teiichi , Maejima Taketo , Aizawa Kikuo , Fukuda Takeaki , Watanabe Hidenobu
Published: December 2008

A case is reported of Intra‐abdominal desmoplastic small cell tumor (IDSCT) with biphasic histologic features in a patient with proximal spinal muscular atrophy. The tumor was composed of small epithelial cell nests with spindle cell sarcomatous areas. Both areas were surrounded by a desmoplastic stroma. Immunohistochemical studies revealed reactivity for low molecular weight cytokeratin, epithelial membrane antigen, vimentin, desmin and Leu‐7 in both areas. Electron microscopic examination demonstrated paranuclear aggregates of intermediate filaments, zonula adherens and basement membrane‐like material in the epithelial cells, while spindle cells in the tumor had fewer intracytoplasmic organelles. However, intermediate or transitional forms of both types of tumor cells were frequently observed. Although IDSCT are known to express multiphenotypes immunohistochemically, attention should be paid to the broad spectrum of cell morphology in these tumors.
Mammary hamartoma: immunohistochemical study of two adenolipomas and one variant with cartilage, smooth muscle and myoepithelial proliferation
Authors: Hayashi Hiroyukl , Ho Takaaki , Matsushita Kazuhiko , Kitamura Hitoshi , Kanisawa Masayoshi
Published: December 2008

Three cases of mammary hamartoma were investigated Immunohlstochemically and are described. Case 1 was a 42 year old woman with an elastic hard tumor, 1.5 cm in diameter, in her left breast. Case 2 was a 49 year old woman with a semisoft tumor, 5 times 2 cm, in her right breast Case 3 was a 47 year old woman with a hard tumor, 5 cm in diameter, in her left breast. In each case, mammography and ultrasonography revealed a benign‐looking, well‐circumscribed mass without calcification. Histologically, the tumors were composed of adipose tissue, mammary glands, and fibrous and/or fibromuscular tissue. The tumor in case 3 also contained small islands of hyaline cartilage. Immunohistochemical analysis was performed, and epithelial and mesenchymal components were discretely and differentially immunostained except that the smooth muscle component seemed to be derived from myoepithelial cells. Cartilage formation might be the result of metaplasia, and ‘metaplastic variant of the mammary hamartoma’ or ‘choristoma’ may be an appropriate term for cartilage‐containing mammary hamartoma. Using proliferating cell nuclear antigen (PCNA)‐lmmunostaining, we observed that each component of the tumors had an individual growth rate. This finding may reflect one aspect of the biological characteristics of hamartoma.
Nodular pulmonary amyloidosis associated with asbestos exposure
Authors: Hiroshima Kenzo , Ohwada Hidemi , Ishibashi Masahiko , Yamamoto Naoyoshi , Tamiya Norihisa , Yamaguchi Yutaka
Published: December 2008

A 71 year old man was admitted for the purpose of diagnosis of a right solitary pulmonary nodule. The size of the nodule was 18 times 18mm in diameter 2 years ago, but It has become large, 25 times 25 mm In diameter. The nodule was resected by thoracotomy. Microscopically, eosinophilic amorphous, acellular substances were surrounded by inflammatory infiltrates. It stained with Congo red stain and showed green birefringence with polarizing microscopy. Amyloid fibrils were observed electron microscopically. Asbestos bodies were observed in the lung parenchyma around the nodule. This case shows that a nodule in nodular pulmonary amyloidosis can grow gradually and suggests the possibility of asbestos fibers as one of the etiologic factors in nodular pulmonary amyloidosis.
A case of malignant transformation in thoracic vertebral hemangioma following repetitive irradiation and extraction
Authors: Obana Yasuro , Tanji Kurenai , Furuta Itaru , Yamazumi Toshiaki , Hashimoto Shigeo , Kikuchi Hiraku , Tanaka Seisuke , Ohba Yasuhiro
Published: December 2008

We report a rare case of thoracic vertebral hemangioma which developed into angiosarcoma during the course of repetitive operations and irradiation. A 44 year old female was operated on for hemangioma of the first thoracic vertebra. The diagnosis of hemangioma was confirmed histo‐pathologically with the specimen from the first operation. The tumor developed multiple lesions later in the clinical course after the first operation, these lesions were removed in four consecutive operations and each histologlcai diagnosis was that of hemangioma. Throughout the period of these operations, the patient was treated wtih steroid, and with radiotherapy simultaneously. The patient underwent the fifth operation for the recurrence of the tumor on 26 March 1990, and the histopathological diagnosis was not hemangioma but hemangiosarcoma which was considered a malignant transformation. The tumor cells immunohistochemically revealed positive staining with UEA‐I, Factor‐VIII, as the tumor immunohistochemically showed a vascular endothe‐lioid nature.
Ossifying fibromyxoid tumor of the retroperitoneum
Authors: Motoyama Teiichi , Ogose Akira , Watanabe Hidenobu
Published: December 2008

A case of ossifying fibromyxoid tumor (OFMT) in an unusual site, the retroperitoneum, in a 71 year old Japanese man Is reported. The well demarcated tumor contained a large amount of mature bony tissue within the tumor. The tumor cells were round to spindle‐shaped, and showed a high cellularity in some areas and were loosely arranged in other areas. Although the majority of tumor cells expressed vimentin, neuron specific enolase and Leu‐7, there were no tumor cells positive for S‐100 protein, myogenic or epithelial markers. We would like to emphasize that tumors classified as OFMT contain a wide spectrum of histologic features and heterogeneity.
Fibrolamellar hepatocellular carcinoma: A case report of a resected with an electron microscopic and flow cytometric analysis
Authors: Hasegawa Akio
Published: December 2008

A resected case of fibrolamellar (FLC) and hepatocellular (HCC) combined carcinoma arising In a non‐cirrnotic liver of a 29 year old female is reported, Including results of the preoperative percutaneous aspiration biopsy, which suggested FLC, and postoperative electron microscopic and flow cytometric analysis. Sections of the resected massive tumor of the left lobe of the liver showed hepatocellular carcinoma accompanying the fibrolamellar carcinoma element which was composed of tumor cells with eosino‐philic granular cytoplasm and unique cytoplasmic vacuoles (pale bodies). Lamellar fibrosis was present in the stroma, while no macroscopic central scar was demonstrated. Electron microscopy showed typical features of FLC and flow cytometric ONA analysis indicated diploid ONA pattern with a low proliferation rate. A common HCC element with trabecular structure also existed at the periphery of the tumor. No apparent etiologic agent for the development of hepatic neoplasm was Indicated In the history of this patient. She had been without recurrence for about 3 years after extended left tobectomy, when local recurrence was revealed. The recurrence has been treated with chemoembolization and percutaneous ethanol infusion several times up till the present. This case reconfirms the importance of the pathological diagnosis of FLC to promote surgical intervention.
Genetic predisposition to lymphomas in mice
Authors: Hiai Hiroshi
Published: December 2008

The spontaneous mouse lymphoma is a model of multlfactorial genetic disease. It is induced by the endogenous murlne leukemia vlrus (MuLV), whose genome is Inherited as a Mendelian dominant trait Lymphoma development takes place in multiple stages affected by many host genetic and epigenetic factors. An inbred strain SL/Kh with a high incidence of pried lymphomas has been established and the genetic predisposition of SL/Kh mice to lymphomas is being studied in the crosses with other inbred strains of mice. In the cross to the NFS/N lacking endogenous MuLV genome, it has been shown that lymphomas are induced by the expression of Emv‐11 provirus (Chr. 7), and the types of 9‐lineage lymphomas are determined by combinations of the host genes, Esl‐1 (Chr. 17) and Foc‐1 (Chr. 4). Another gene, Tlsm‐1 (Chr. 7) that determines the type of lymphomas to be T‐lineage, is identlfied In the cross with AKR/Ms, with a high incidence of T‐lymphomas. The role of the thymus In the development of T‐lymphomas in the mouse, and the posslble relevance of Tlsm‐1 in this step, is discussed. The length of the latent period is determined by a gene Ua‐1 (Chr. 17). A maternal resistance factor that is a maternal antibody to MuLV transmitted via milk and that epigenetically inhibits MuLV expression In SL/Ni‐Eco, one of subline of SL/Ni mice, has been shown. Weak but definitive maternal resistance also operates In SL/Ni‐Eco+, a subline lacking the maternal antibody to MuLV. In the latter, there is a recessive resistance gene Nir‐1 (Chr. 4). In the cross with MSM/Ms, a wild mice‐derived inbred straln, two resistance genes, Msmr‐1 (Chr. 17) and Msmr‐2 (Chr. 18), have been identified. In SL/Kh, all of these host genetic and epigenetlc factors are favorable for lymphoma development. This model Offem not only an understanding of the pathogenesis of virus‐induced lymphomas but also may provide starting material for the comparative approach to homologous human diseases.
Establishment of a therapeutic model for retroviral infection using the genetic resistance mechanism of the host
Authors: Kitagawa Masanobu , Aizawa Shiro , Ikeda Hidetoshi , Hirokawa Katsuiku
Published: December 2008

Resistance to retroviral infection is often regulated by multiple genes that control different aspects of the host‐virus interaction. Genetically distinct inbred strains of mice differ in their susceptibility to retrovirus and have allowed the identification of several host‐resistant loci that regulate the host defense mechanism to retroviral Infection. Using the murine retrovirus infection system, a therapeutic model has been developed of retrovirus Infection In association with the resistant mechanism of host genes. The most effective result achieved with the model was when using bone marrow transplantation of retrovirus‐reslstant cells with receptor interference function, which was genetlcally defined by the Fv‐4 resistant gene. The possible appllcatlon of these findings to the gene therapy of retrovirus‐induced disease of humans Is discussed.
Prohormone convertases (PC1/3 and PC2) in rat and human pancreas and islet cell tumors: Subcellular immunohistochemical analysis
Authors: Itoh Yoshlko , Tanaka Shigeyasu , Takekoshi Susumu , Itoh Johbu , Osamura R. Yoshiyuki
Published: December 2008

Prohormons convertase 1/3 (PC1/3; also termed PC1 or PC3) and PC2 are enzymes that activate prohormones by cleaving the pairs of basic amlno acids. This mechanlsm was inltlally Interred lrom the series of several endocrine and neuroendocrine precursor protoh, inciudlng proinsulin and prolusion. To determine the cellular and sub cellular distribution of PC1/3 and PC2 in the rat snd human pancreas, Immunohlstochemistry was performed using polyclonal antlers against mouse PC1/3 (ST‐28) and mouse PC2 (ST‐29). These studles showed light and dsctron mlcroacoplc co‐locailzation of Insulln, PC1/3 and PC2, and the coexistence of glucagons and PC2 In the pancreatic islets. This tendency of colocalizstion was also depicted In one case of human insulin and three cam of human glucagonomas, as well as In rat Insullnomas. in two cases of human Insullnomas, Incomplete processing of proinsulin was suggested by the absence of PC2. At the sub cellular level in the rat pancreatic lslet, the colocalizstion of PC1/3 and insulin, and that of PC2 and glucagons, were observed in the same secretor granules by immunoelectron, microscopy and Image analysis. These studles suggest that PC1/3 and PC2 can functlon with the specifictties In the processing of proinsulin and proglucagon Into their active forms, respectively, in the normal and neoplastic pancreatic islets.
Immunohistochemical study with anti‐advanced glycation end‐products antibody in murine amyloidosis
Authors: Hoshii Yoshinobu , Kawano Hiroo , Gondo Toshikazu , Takahashi Mutsuo , Ishihara Tokuhiro , Higuchi Keiichi , Hotiuchi Seikoh
Published: December 2008

Advanced glycation end‐products (AGE) are formed In the late phase of the non‐enzymatic glycosylation reaction in conditions such as diabetes mellitus and aging. In amyloidosb, AGE have been twnd In the Aβ2M amyldd associated with long‐term hemodlalysls and in the β‐protein in Alzheimer's disease. Murine AApoAll and AA amyloidosls were examined lmmunohistochemically using anti‐AGE monodonal antibody, 6D12. AApoAll amyloid deposits studied in one smeaconm‐accelerated mouse P1 (SAMP1), congenic mice that have the amyloldogenic apollpoprotein A‐ll of SAMP1 mice, and AKR mice all reacted with blotinylated 6D12 by formic acid pretreatment, whereas AA amyloid deposits did not react with the antibody. The immunoreaction wlth anti‐apollpoprotein A‐II for amyloid deposits in senile mice was approximately homogeneous in intensity; on the other hand the reaction with biotinylated 6D12 was irregular in distribution and intensity over the amyloid deposits. These findings suggest that amyloid precursor proteins are not associated uniformly with AGE modification before deposition as amyloid; it Is more likely that the AGE modification progresses gradually and unevenly after amyloid deposition. Murine amyloldosis may be a useful model to elucidate the role of AGE in amyloidosis.
Advanced glycosylation end‐products and heat shock proteins accumulate in the basophilic degeneration of the myocardium and the corpora amylacea of the glia
Authors: Iwaki Tow , Harnada Yasuhiro , Tateishi Jun
Published: December 2008

Uslng monospecific antibody for the advanced glycosylation end‐products (AGEP), It was revealed that the AGEP localized in the basophllic degeneration of the myocardium and the corpora amylacea of the glia. The stability of the proteins that constitute those degenerative deposits suggests that they would be Ideal substrates for non‐enzymatic glycation, a process that occurs over a long the under a high glucose content, and ultimately results in the formation of the AGEP. Such deposlts also exhibited evidence of stress reactions: the accumulation of HSP72, heme oxygenase‐1 and ublquitin. As recent studies have shown that AGEP‐modified proteins aggregate and that they generate reactive oxygen intermediates, the accumulation of such heat shock proteins may reflect the oxidative stress concomitant with AGEP accumulation, and thereby promote their cellular dysfunction. Hereby, it is proposed that the age‐related increase in the AGEP, that is, a fundamental aging process, is involved in the formation of the basophllic degeneration in the myocardium and the corpora amylacea of the glla.
Both acute phase and constitutive serum amyloid A are present in atherosclerotic lesions
Authors: Yamada Toshiyuki , Kakihara Toshio , Kamishima Tomoko , Fukuda Takeaki , Kawai Tadashi
Published: December 2008

The polymorphic protein, serum amyloid A (SAA), consists of acute phase Isotypes and a constitutive Isotype. Both are associated mostly with high density lipoproteins (HDL) In the circulation. In the present study, both SAA isotypes were detected by Immunohistochemistry and Immunoblotting using monocional antlbodies In atherosclerotic lesions. As the distribution of SAA was identical with that of apolipoprotein B and SAA is known to be associated also with low density lipoproteins (LDL), SAA may also be delivered to the artery wall by LDL.
Simplified rapid non‐radioactive PCR‐SSCP method applied to K‐ras mutation analysis
Authors: Yamashita Kazuya , Tatebayash1 Taeko , Shinoda Hiroshi , Okayasu Isao
Published: December 2008

A newly modified non‐RI, PCR‐SSCP method Is presented and applied to K‐ras analysis of colorectal tumors. It comprises five steps: (1) sampling of tiny pieces of fresh solid tissue by scraping with disposable bamboo combs (thin bars made of bamboo, 3×3×120 mrn In size); (2) one‐step DNA extraction with lysls buffer containing proteinase K, Nonidet P40 and Tween 20; (3) PCR with 108bp, c‐ki‐ras 2 gene primers; (4) SSCP analysis with 10% forrnamlde‐added poly‐actylamide gels; and (5) detection with silver staining. In comparison with conventional RI‐ or non‐RI‐PCR‐SSCP, it can give reliable and clear results in a much shorter time (within a total of 6h). This novel approach should allow more frequent use of molecular diagnosis in biopsies and surgical pathology.
Morphology, function and pathology of follicular dendritic cells
Authors: Imai Yutaka , Yamakawa Mitsunori
Published: December 2008

The precise ultrastructural morphology and functions In reactive conditions of lymphoid follicles (LF) and dendritic cells, including follicular dendrltic cells (FDC) are reviewed; as Well as the pathognomonic role of FDC In some disease conditions and finally, the cellular origin of FDC. In reactive conditions, FDC In each of the fivre follicular zones have distinct ultrastructural features, retlecting the different three dimensional structures and functions of these zones. The FDC framework may be supported by some characteristic factors, including desmosome‐like junctions between FDC and the expression of flbronectin and laminin receptors and caldeasmon on FDC. FDC, especially In the light zone, express various cytokine receptors, but produce only one cytokine, TGF‐β. The outer zone may not only be a cellular pathway in the LF, but may also provide a site for germinal center B cell prollferation, and the FDC‐lymphocyte cluster Is not the site of germinal center B cell division. In patients with autoimmune diseases, such as Hashimoto's thyroiditis and rheumatoid arthritis, FDC may be in a hyperfunctional state, whereas those In patients w*H immunosuppressive disorders, such as Kimura's disease and AIDS, may be in a dysfunctional state. FDC may be derived from fibroblastic reticulum cells in lymphatic tissues rather than in bone marrow cells. The data discussed In this retview provide fascinating insight into the roles of FDC, which are intimately related to the migration, proliferation, cell selection and differentiation of B cells in secondary LF.
Molecular pathogenesis of adenoma and differentiated adenocarcinoma of the stomach
Authors: Tamura Gen
Published: December 2008

Advances In molecular biology have revealed a consistent set of genetic aiterations that may correspond to multistep tumor development. The pathogenesis of adenoma and differentiated adenocarcinoma of the stomach are reviewed from a genetic perspective with reference to the colorectal adenoma‐carcinoma sequence. The sequential accumulation of genetic alterations characteristic of the colorectal adenoma‐carclnoma sequence does not occur between sdenoma and differentiated adenocarclnoma of the stomach, although adenomatous polyposis coli (Am) mutation in adenoma, and p53 mutation and loss of heterozygosity (LOH) of DCC (deleted In colorectal cancer) gene in carcinoma are prevalent genetlc alterations. Allelotype, LOH and micro‐satelllte anatyses have revealed several chromosomal regions of ddetlon, as well as genetic Instability, that accumulate during the development and progression of differentiated adenocarcinomas. However, these alterations are rarely found In adenomas of the stomach. These findings suggest that the adenoma‐carcinoma sequence Is relatively rare in gastric carcinogenesis, and that most differentiated adenocarcinomas of the stomach develop through a de novo pathway.
Pathological diagnosis of Alzheimer‐type dementia for old‐old and oldest‐old patients
Authors: Mlzutanl Toshio
Published: December 2008

The pethological dlagenosis of Alzhelmer‐type dementia (ATD) is reviewed. The problems wlth the quantitative diagnosis are threatdd: the number of the senile planues (SP) is not always related to the presence or the absence of dementia; recent research indicates that the SP and the neuroflbrillary tangles (Nm could represent a different level in the pathogenesis of ATD, and flnally it has not beem seriously discussed whether ATD is the final stage of physiological aging or if ATD Is a definitive disease. For these reasons, new diagnostic criteria are proposed in order to differentiate ATD from physiological aging. The new crlteria are suitable even in the oldold and oldest‐old patients. It is stressed that ATD Is heterogeneous in the pathogenetic aspect, consisting of Alzheimer's disease with onset before the age of 70 years (the neocortlcal type of ATD) and senile dementia of the Alzheimer type (the limbk type of ATD) with the onset after the age of 70. Even In cases with the latter type, there are several atypical ATD and non‐ATD forms. ‘Primary senile dementia’ Is proposed as a comprehensive term to include various types of senile dementia of unknown etiology.
Protein‐losing enteropathy due to intestinal lymphangiectasia accompanied by mesenteric lymph node fibrosis
Authors: Nakano Shigeo , Kuramochi Shigeru , Hosoda Yasuhiro , Miura Soichiro
Published: December 2008

An autopsy case of a 74‐year‐old man suffering from edema In the legs and diagnosed as protein‐losing enteropathy due to intestinal lymphanglectasla Is presented. He underwent a radlcal operatlon and radiotherapy for esophageal carcinoma at age 65 years and the onset of proteln‐losing enteropathy was at age 70. Postmortem examination disclosed widespread abnormalities of the duodenal and small intestinal lymphatics and mesenteflc lymph node flbmsls. The mucosal lymphatic capillaries were markedly dilated. In the sub‐mucosal and serosal layers, the lymphatic vessels showed marked dilatation in some areas and fibrous occlusion with very thick muscle layers in others. All these lymphatic changes were presumed to be attributable to a reactive process secondary to lymph congestion, which it is suggested, was caused by the mesenteric lymph node fibrosis.
Primary carcinoid tumor of the kidney with special reference to its histogenesis
Authors: Takeshima Yuklo , Inai Kouki , Yoneda Kenji
Published: December 2008

A case of primary carclnoid tumor of the kidney occurring In a 6&yeard women b reported. The tumor was 10 times 10 times 9 cm In she, did, yellowlsh‐white In color, and associated with nuuslve hemorrhagk necrosis. Hlstoluglcally, it was composed of trebecular and anastornosing ribbonlike nests. The tumor cells showed argyrophllbity with the Grlmelius stain and cytoplasmlc PCwitMty for neumendocrlne markers, (Including chromogranln A, neuron‐specifie endase, synap tophysln and Leu‐7), prostetlc acid phosphatase, keratin and vimentln. Numerous cytoplasmlc neurosecretory granules were demonstrated uhstmcturally. These histologic and Immunohistochemical findings are consisten with the theory that this tumor has a common phenotype with that of carcinoid tumor aridng from the hlndgut or cloaca.
Recommendations for the reporting of urinary bladder specimens containing bladder neoplasms Association of Directors of Anatomic and Surgical Pathology
Authors: Fechner Robert E.
Published: December 2008

The Assoclatlon of Directors of Anatomic and Surgical Pathology have developed recornmendatlons for the surgical pathology reporting of common malignant tumors. The recommendations for carcinomas of the urinary bladder are reported herein.
Role of c‐kit receptor tyrosine kinase in the development, survival and neoplastic transformation of mast cells
Authors: Tsujimura Tohru
Published: December 2008

The c‐kit gene is allelic with the dominant spotting (W) locus on mouse chromosome 5 and encodes a receptor tyrosine kinase. The llgand for c‐klt receptor is stem cell factor (SCF), which is the principal growth factor for mast cells. The loss‐of‐function mutations of c‐kit receptor affect the development of mast cells, thereby resulting in a depletion of mast cells. The abundant expression of c‐ktt receptor is indispensable for the survival of mast cells. In addition, the galn‐of‐function mutations of c‐kit receptor were found in several tumor mast cell lines. When these galn‐of‐function mutations were introduced to cells of murine interleukin (IL)‐3‐dependent cell lines, the expression of c‐kit receptor with constitutive tyrosine kinase activity not only abrogated the IL‐3 requirement of the cells, but also caused them to become tumorlgenic in nude athymic mice. The gain‐of‐function mutations of c‐kit receptor appear to result in the malignant transformation of mast cells. Taken together, the signals from the c‐ktt receptor are essential for the development, survival, and malignant transformation of mast cells.
Insular component as a risk factor of thyroid carcinoma
Authors: Sasaki Atsushi , Daa Tsutomu , Kashima Kenji , Yokoyama Shigeo , Nakayama Iwao , Noguchi Shiro
Published: December 2008

Forty‐four thyroid carcinomas with an Insular component (JC) were reviewed from 2457 tumors diagnosed as papillary (PC) or follicular carcinoma (FC). These tumors were classified as FC with an IC (FCIC; 30 cases) and PC with an IC (PCIC; 14 cases). Both tumors were composed of solid cell nests in some areas and had a tendency toward a characteristic nuclear size: FCIC had a small nucleus and PCIC contained a nucleus of an Intermediate type or a large nucleus similar to that of PC, although there were numerous tumors with an exceptional nuclear size. The mean age and tumor diameter were the highest and largest in FCIC, respectively, followed by PCIC. Among the 44 cases, 17 patients died of the disease, two were alive with the disease and 18 were alive without the disease. From 13 clinicopathological factors, the presence of an IC, age, non‐encapsulation, tumor size, vascular invasion and necrosis were found to be independent variables for actual prognosis of FC and PC based on univariate analysis followed by multtvariate analysis. The results of the present study indicate that the presence of an IC is an independent aggressive prognostic factor for patients with PC and FC.
Clinicopathologic study of 97 cases of small renal cell carcinomas using DNA flow cytometric analyses
Authors: Shishikura Yuri , Suzuki Masafumi
Published: December 2008

The incidence of small renal cell carcinomas (RCC) has Increased recently as diagnostic imaging techniques have improved. The Indications for partial nephrectomy for small RCC confined to the kidney are still controversial. Ninety‐seven small RCC 2.5 cm or smaller, Including incidental, occult, and dialysis associated carcinomas obtained at surgery or autopsy were examined. Various clinicopathologic parameters were assessed and survival was analyzed using the Kaplan‐Meir method. Seventy‐eight cases were incidental carcinomas. Carcinomas caused death in five cases, four of which had Initial signs of metastatic disease. Differences in survival between patients with expansive and invasive (intermediate and infiltrating) growth patterns, solid and other structural patterns, clear and other cell types, grade 1 and higher grades of nuclear atypla, and with and without lymph node metastasis were statistically significant All surgical cases were alive except one who died of another disease. Poor prognostic factors seen in five fatal autopsy cases included invasive growth pattern, solid structural pattern, spindle cells, grade 3 nuclear atypia, and Bellini duct carcinoma. Small RCC may be treated with partial nephrectomy provided they do not show these features, although there is low risk of recurrence or development of de novo cancer.
Proliferation marker MIB‐1 correlates well with proliferative activity evaluated by BrdU in breast cancer: An immunohistochemical study including correlation with PCNA, p53, c‐erbB‐2 and estrogen receptor status
Authors: Moriki Toshiaki , Takahashi Tamotsu , Kataoka Hiromi , Hiroi Makoto , Yamane Toshiko , Hara Hiroshi
Published: December 2008

The proliferative activity of 30 cases of non‐treated invasive ductal breast carcinoma was evaluated by bromodeoxyuri‐dine (BrdU), proliferation marker (MIB‐1) and proliferating cell nuclear antigen (PCNA), and the relation between these proliferation markers and histologlcal subtype and histolog‐ical grade were investigated. In addition, the association of these proliferation markers with overexpression of p53 protein, c‐erbB‐2 oncoprotein, estrogen receptor (ER) status and clinicopathologic findings were also examined. The BrdU labeling index (LI), MIB‐1 score and PCNA labeling rate (LR) correlated with the histological grade. However, there was no statistical difference in proliferative activity among the histological subtypes. A linear strong correlation was demonstrated between BrdU Li and MIB‐1 score (r=0.732). Significant correlation was also found between BrdU LI and PCNA LR (r=0.446); however, the relation between MIB‐1 score and PCNA LR was weak. BrdU LI and MIB‐1 score correlated positively with tumor size, TNM stage and over‐expression of p53, and negatively with the presence of ER. PCNA LR correlated only with p53. These results indicate that MIB‐1 is closely associated with BrdU in clinicopathologic findings and is a more useful tool for evaluating cell proliferation than PCNA. However, it will be necessary to consider the clinical significance of MIB‐1 immunohisto‐chemistry cautiously until further widespread clinical and pathological studies are performed.
Synergistic effects of erythropoietin and interleukin‐6 on the in vitro proplatelet process formation of rat megakaryocytes
Authors: Tange Tsuyoshi , Miyazaki Hiroshi
Published: December 2008

The racombinant hemopolettc factors of megakaryocyte potentlator (MEG‐POT) were studied to compare their activity In stimulating proplatelet process formation (PPF) with thrombopoletln (TPO, c‐MpI Itgand). For the assay, a highly enriched (>95%) population of more than 90% viable megakaryocytes was Isolated from rat bone marrow using the Immunomagnetic beads method and cultured with fetal calf serum (FCS) or In a serum‐free condition. Megakaryocytes developing slender beaded cytoplasmic processes (proplatelet processes) were observed on both inverted phase contract microscopy and scanning electron microscopy. A large number of proplatelet process clusters were dose‐dependently formed with the addition of varying doses of recombinant erythropoietin (rEpo) and interleukin‐6 (rlL‐6) as well as TPO. Epo and IL‐6 were demonstrated to act synergistically solely at low doses in the development of PPF (P<0.05). Other recombinant factors such as IL‐11, leukemia inhibitory factor (LIF) and erythroid differentiation factor (EOF) appeared weak or ineffective. From these In vitro observations, It was suggested that a synergism of Epo and IL‐6 might play a significant role in the terminal stage of megakaryocyte maturation leading to platelet release.
Biased VH family usage in primary gastric B cell lymphoma of mucosa‐associated lymphoid tissue‐type and the selected Vβ expression of T cells infiltrating into the lymphoma cells
Authors: Shibata Takao , Ohshima Koichi , Kikuchi Masahlro
Published: December 2008

Seven cases of primary gastric low‐grade B cell lymphoma of mucosa‐assoclated lymphoid tissue (MALT) type, two cases of high‐grade B cell lymphoma with a low‐grade component and three cases of pure high‐grade lymphoma were selected for the current study. The Ig VH gene use of lymphoma cells and the Vβ repertoires of infiltrating T cells were Investigated. The VH gene analysis showed multiple VH family usage In 12 cases, but the MALT‐type lymphoma cell usage was found to be biased for the families that have a low number of VH genes (VHIV and V). Another analysis of lymphoma‐lnfiltrating T cells showed restricted expressions of the Vβ repertoire in all seven low‐grade cases and three high‐grade cases. In those 10 cases, a considerable number of CD4‐postttve T cells Infiltrated Into lymphoma cells and RAG‐1 was also prominently expressed. Based on these findings, It was thus assumed that the normal counterpart of gastric B cell lymphoma of MALT type is different from the conventional B cell lymphoma, and the restricted expression of Vβ repertoires Is therefore considered to be a characteristic finding in low‐grade B cell lymphomas of MALT type as well as in a proportion of high‐grade lymphomas (the so called ‘high‐grade lymphoma of MALT type’).
Difference in the three‐dimensional structure of the sinusoids between hepatocellular carcinoma and cirrhotic liver
Authors: Shimizu Hideo , Suda Koichi , Yokoyama Takeshi
Published: December 2008

The purpose of the present study was to estimate the difference in three‐dimensional (3‐D) structure of sinusoids between hepatocellular carcinoma (HCC) and cirrhotic liver, by the use of topology. Ten surgically resected lesions of HCC and 10 lesions of liver cirrhosis (LC) were used. Computer‐alded reconstruction models of HCC sinusoids and LC sinusoids were developed from 20 4μm thick serial tissue sections from each specimen. A topologlcal invariant, called the first Bettl numberp., was used to estimate the complexity degree of the 3‐D sinusoidal structure. The mean p, of the sinusoidal network in the examined tissue, 200X200X80 μm3 in size, was 46.5X33.0 In 10 HCC and 84.9 ±19.1 in 10 cirrhotic livers. There was a statistically significant difference between the two values (P<0.01), while there was no significant difference in the sinusoidal volume of the same size tissue between the HCC and the cirrhotic liver. It was found, therefore, that the sinusoidal network of HCC was more sparsely and coarsely knit in 3‐D space than that of the cirrhotic liver.
Hepatoblastoma in an adult associated with c‐met proto‐oncogene imbalance
Authors: Kuniyasu Hiroki , Yasui Wataru , Shimamoto Fumio , Fujii Kiyomu , Nakahara Masahiro , Asahara Toshimasa , Dohi Kiyohiko , Tahara Eiichi
Published: December 2008

A rare case of hepatoblastoma in a 61‐year‐old Japanese housewife is described. This liver tumor mainly consisted of two tissue components: embryonal hepatocytes and primitive mesenchymal tissue. Fetal hepatocytes with alpha‐fetoprotein production, gland formation, cartilage and osteoid were also found in a small portion. Molecular analysis by slot blot method revealed increased copy numbers of c‐met and K‐sam proto‐oncogenes and cyclin D1 genes. These findings suggest that alterations of these oncogenes might play a role in the development of adult hepatoblastoma.
Adenomyoepithelioma of the breast with exaggerated proliferation of epithelial cells: Report of a case
Authors: Nomura Kouichi , Fukunaga Masaharu , Uchida Ken , Aizawa Shigeo
Published: December 2008

A case of adenomyoepithelioma of the breast in a 58‐year‐old woman Is described. The tumor was a solitary, solid mass measuring 35X30 mm. Hlstologically, the tumor was composed of a proliferation of both epithelial and myoeptthelial cell components. The epithelial cell component showed extensive columnar cell change with clear cytoplasm and focal exaggerated proliferation with cytologic atypia and increased mitotic figures. DNA ploldy analysis revealed aneuploidy. DNA ploldy analysis might be used to predict the biological behavior of adenomyoepithelioma.
Cell renewal and functional morphology of human lactating breast: Presentation of a new mode of cell death (‘magentosis’) characterized by nuclear periodic acid‐Schiff reactivity
Authors: Umemura Shinobu , Osamura R. Yoshiyuki , Tsutsumi Yutaka
Published: December 2008

Cell kinetics and functional morphology of the human lactating breast were analyzed using 21 paraffin‐embedded specimens of the lactating breast obtained by biopsy or surgery and two of the ‘resting’ breast. Four types (I‐IV) of lactating lobules were categorized histologically, and were well correlated with their functional status demonstrated by Immuno‐hlstochemistry for epithelial membrane antigen, β‐casein, lipase, lactoferrin, secretory component and IgA. Type I corresponded to a pre‐lactating state, type II to an actively lactating state, type III to an early stage of regression, and type IV to an advanced stage of regression. Cell proliferation monitored by Ki‐67 (MIB‐1) immunostainlng was at the highest level in type I lobules followed by type IV, while the labeling indices were low in types II and III. Apoptosis demonstrated by terminal deoxynucleotldyl transferase (TdT)‐mediated deoxyuridine triphosphate (dUTP)‐biotin nick end‐labeling (TUNEL) method showed labeling profiles comparable with the proliferative activity. Hoiocrine‐type desquamative cells with intact‐appearing nuclei were frequently recognized in type II lobules. In type III, a peculiar form of cell death, designated ‘magentosis’, was demonstrated. These degenerative cells occasionally shedding into the acinar lumen possessed homogeneous pale, TUNEL‐negative nuclei with diastase‐resistant periodic acid‐Schiff (PAS) reactivity. ‘Magentosis' specifically identified in an early phase of involution of the human lactating breast might represent a unique mode of cell death distinguishable from apoptosis and necrosis.
The relationship between the gene mutation of p53 and the protein expression of p53 and Ki‐67 in non‐Hodgkin's iymphomas
Authors: Kuze Tetuo , Nakamura Naoya , Hashimoto Yuko , Hojo Hiroshi , Abe Masafumi , Wakasa Haruki
Published: December 2008

The relationship between the mutation of the p53 gene and the expression of the p53 protein and the Ki‐67 antigen has been investigated In 115 cases with non‐Hodgkin's lymphoma, using the immunohlstochemical double staining technique, single‐strand conformatlonal polymorphism and DNA sequencing methods. Eighteen cases showed more than 10% of p53+ cells and the others showed a few p53+ cells presented sporadically. Alterations In the p53 gene were detected in six cases with B cell type, consisting of five cases with point mutation and one case with point mutation and 15 base pairs deletion. These six cases showed a high percentage of p53+ cells and five cases revealed that the percentage of p53+ ceils was higher than that of Ki‐67+ cells (p53+ cells > Ki‐67+ cells). Excluding the six cases wtth mutation of the p53 gene, all cases revealed that the percentage of p53+ cells was less than that of Ki‐67+ cells (p53+ cells < Ki‐67+ cells). Moreover, there was a positive correlation between expression of the p53 protein and of the Ki‐67 antigen in histologic types of B cell Iymphomas and of T cell Iymphomas, respectively, except in small non‐cleaved (Bur‐kitt's) and lymphobiastic types. Therefore, sporadic cases showing p53+ cells > Ki‐67+ cells revealed alteration of the p53 gene, and expressed abnormal p53 protein (mutant form). Most cases showing p53+ cells < Ki‐67+ cells expressed normal p53 protein (wild type), and may reflect the rapid proliferation rate.