bluuebunny/crossref_metadata_2025 huggingface dataset:
Reticulohistiocytoma involving the skin, subcutaneous tissue and a regional lymph node
Authors: Suwabe Hisako , Tsutsumi Yutaka
Published: December 2008

A 30‐year‐old female complained of a surface‐eroded solitary nodule on the right thigh. Hlstologlcally, the dermal lesion consisted of uniform‐sized polygonal cells with eosinophlllc, ‘ground glass’ cytoplasm. Mitoses were infrequent. Under the histopathologlc diagnosis of amelanotic melanoma, wide resection of the skin and dissection of the inguinal lymph nodes were performed. The subcutaneous tissue and a lymph node showed nodular proliferation of histiocytold cells, in association with hemosidertn‐laden multinucleated giant cells. The mononuclear cells were immunoreactlve for factor Xllla, while the multinucleated cells were positive for CD68, lysozyme and HLA‐DR. In the lymph node tissue, a considerable number of mononuclear cells positive for CD68 were noted. CD34, α‐smooth muscle actin, desmin and HMB45 were negative. Ultrastructurally, the mononuclear cells were rich In 100 nm vesicles and 180–350 nm lysosome‐like granules. Interdigitation of the plasma membranes was seen in the multinucleated cells. The patient did not complain of Joint symptoms, and has been disease‐free for 5 years. The histo‐logic and immunohistochemical features are consistent with so‐called ‘reticulohistiocytoma’, though the site of histiocytic growth was unusual.
Adenocarcinoma arising within a colonic diverticulum
Authors: Kajiwara Hiroshi , Umemura Shinobu , Mukai Masaya , Sadahiro Sotaro , Tsutsumi Yutaka
Published: December 2008

A case of cancer arising in a diverticulum of the ascending colon In a 67‐year‐old male is reported. The 1.5 × 1.0 cm well‐differentiated adenocarcinoma protruded from the base of the inverted mucosa of the diverticulum. The surrounding flat colonic mucosa was not involved by the cancerous process. Focal stromal invasion was seen in the subserosal tissue, without association of lymph nodal involvement. This is the third reported case of adenocarcinoma arising in the colonic diverticulum.
A study of the development of atherosclerosis in childhood and young adults: Risk factors and the prevention of progression in Japan and the USA
Authors: Komatsu Akio , Sakurai Isamu
Published: December 2008

Coronary heart disease (CHD), one of the prevalent results of atherosclerotic disease, has been a leading cause of death in many Western countries for several decades, and now is the second most prevalent cause of death in Japan. Thus attention must also be paid to atherosclerosis in Japan. While there has been a remarkable reduction in the mortality rate from CHD in some Western Countries, an undesirable stabilized mortality rate has recently been reported by the government of Japan. This report emphasises the importance of preventing atherosclerosis at an early stage from the viewpoint of cardiovascular pathology, using evidence from statistical data derived from autopsied cases in Japan and the USA.
Epstein‐Barr virus‐associated post‐transplant primary smooth muscle tumor of the liver: Report of an autopsy case
Authors: Sadahira Yoshito , Moriya Takuya , Shirabe Teruo , Matsuno Tsuyoshi , Manabe Toshiaki
Published: December 2008

Epstein‐Barr (EB) virus‐associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus‐associated smooth muscle cell tumor in a 21 year old female who received immunosuppres‐sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α‐smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus‐encoded RNA 1 (EBER‐1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo‐grafts, but also in those with renal allografts.
Relapsing hemorrhagic varicella
Authors: Suwabe Hisako , Yabe Hiromasa , Tsutsumi Yutaka
Published: December 2008

A15 year old boy with a past history of chickenpox in infancy was complicated by lethal varicella during the course of chemotherapy against recurrent acute myeloblastic leukemia. He had received allo‐bone marrow transplantation and had overcome a graft‐versus‐host disease. The skin eruptions were hemorrhagic and progressive during the last 3 weeks, with numerous intranuclear inclusions histologically confirmed in the involved epidermis, hair follicles and endothe‐lial cells. lmmunohistochemical and electron microscopic studies confirmed the infection of varicella‐zoster virus.
Immunohistochemical characterization of a case of duodenal gangliocytic paraganglioma
Authors: Furihata Mutsuo , Sonobe Hlroshi , Iwata Jun , Ido Eiji , Ohtsuki Yuji , Ohnishi Sabum
Published: December 2008

A case of duodenal gangliocytic paraganglloma (DGP) arising in the ampulla of Vater of an 84 year old male is reported. The present case shows the typical hlstological features with a mixture of epithellold, gangllon‐like and spindle cells. lmmunohistochemically, the spindle cells were positive with antibodies to neuron specific enorse, S‐100 protein and nsurofilament (NF), but negative for anti‐glial fibrillary acidic protein (GFAP), synaptophyaln and myelln basic protein (MBP). Both anti‐Leu‐7 and chromogranin A antibodies gave porritive reactions with a fine granular pattern in the epithellold cells. Most ganglion‐like cells showed the cytoplasmic lmmunorsection with GFAP and a few with NF and synapto physin. In these three tumor components, no reactivity was detected In the antibodies to the neurohormonal peptides tested. The present data are fundamentally in keeping with those previously reported, but add the immunohistochemical positivity of gangllon‐like cells for GFAP, suggesting different neuroglial differentiation.
Salivary duct carcinoma: A clinicopathologic study of three cases with a review of the literature
Authors: Minamiguchi Sachiko , Iwasa Yoko , Shoji Kazuhiko , Higuchi Kayoko , Watanabe Chihiro , Haga Hironori , Nakashima Yasuaki , Yamabe Hirohiko
Published: December 2008

Three cases of salivary duct carcinoma are presented. They occurred in a 60 year old man, a 66 year old man and a 57 year old woman. All of the lesions were located In the parotid gland. The tumor size ranged from 3 to 5 cm across the largest diameter. Facial paralysis was observed in two cases. Histologically, intreductal and invasive adenocarcinoma showing papillary, cribriform, and solid patterns with comede like necrosis was observed. lmmunohistochemically, the tumor cells were positive for keratin and epithelial membrane antigen. No myoepithelial cells were demonstrated within the tumor by staining for S‐100 protein, α‐smooth muscle actin or muscle specific actin. Ultrastncturally, intracytoplasmic lumina with microvilli, a moderate number of mltochrondria, lysosomes, and tight junctions were found. Regional lymph node metastasis was observed in one case, and distant metastasis developed in two cases. All of me patients were treated with adjuvant postoperative irradiation. One patient died of disease at 11 months after the initial diagnosis, another was alive with disease at 8 months, and the third patient was alive without disease at 2 years and 3 months. Salivary duct carcinoma should be ditterentiated from low‐grade salivary gland carcinomas using morphologic and clinical criteria because of its poor prognosis even with aggressive therapy.
Establishment and characterization of new human Burkitt's lymphoma cell lines (HBL‐7 and HBL‐8) that are highly metastatic in SCID mice: A metastatic SClD mouse model of human lymphoma lines
Authors: Abe Masafumi , Suzuki Osamu , Tasaki Kazuhiro , Abe Rokuo , Wakasa Haruki
Published: December 2008

Two newly established human Burkitt's lymphoma cell lines (HBL‐7 and HBL‐8) were characterized by immunophenotypic, cytogenetic and molecular studies. Both cell lines were negative for Epstein‐Barr virus (EBV) genome and had chromosomal translocation: t(8;14) (q24;q32). Immunoglobulin (Ig) gene rearrangement analyses confirmed that both cell lines were dew from primary lymphoma cells. These cell lines wem heterotransplanted subcutaneously into severe combined Immunodeficiency (SCID) mice to investigate the metastatic capacity. The most striking feature of both cell lines was to show highly spontaneous metastasis to distant organs, particularly spleen, bone marrow and ovaries in SCID mice. To elucidate the metastatic factors involved in the process of spontaneous metastasis, cell surface adhesion molecules or extracellular matrix receptors were analyzed. However, the results did not allow a significant correlation between expression levels of those molecules or matrix receptors and spontaneous metastasis in the SClD mouse model. The HBL‐7 and HBL‐8 cell lines, however, may be a useful tool to elucidate the metastatic mechanisms of human lymphomas in an animal model.
Uterine leiomyosarcoma with osteoclast‐like giant cells: Histopathological and cytological observations
Authors: Watanabe Kazuo , Hiraki Hiroyuki , Ohishi Mari , Mashiko Kazuyuki , Saginoya Hideo , Suzuki Toshimitsu
Published: December 2008

A 56 year old woman presented with abnormal uterine bleeding. Except for a myomatous uterus, no other abnormalities were noted on physical examination and in radiographic and serologic studies. The hysterectomy specimen revealed an 8 cm uterine fundic tumor composed of two histologically different patterns that merged with one another; one was a well differentiated leiomyosarcoma and the other a mixture of osteoclast‐like giant cells (OGC) and plump spindle cells whose cell borders blended, resembling the histology of giant cell tumor of bone. lmmunohistochemical studies showed positive staining for muscle actin, α‐smooth muscle actin, and KP‐1 (CD68) in both the spindle cells and OGC. The latter also stained for α‐1‐antitrypsin and α‐1‐antichy‐motrypsln. These findings suggested that OGC may be formed by the fusion of spindle cells of leiomyosarcoma and also express histiocytic markers.
Expression of mucin antigens in human cancers and its relationship with malignancy potential
Authors: Yonezawa Suguru , Sato Eilchi
Published: December 2008

Mucins are high molecular weight glycoproteins having oligosaccharldes attached to the apomucin protein backbone by Gglycosidlc Inkages. Blochemical studies on the structures and the organ specificities of several much core proteine (MUC1‐MUC7) have been reported during the past several years. In the present study of pancreas and Intrahepatic bile duct tumors, MUCl mucin (membrane bound much detected by monoclonal antibody, DF3) was highly expressed in Invasive ductal carcinomas of the pancreas (IDC) and Invasive cholangiocarcinomas of the liver (CC), which show Invasive growth and a poor prognosis, but it was rarely expressed in intraductal papillary mucinous tumors of the pancreas (IPMT) and bile duct cystadenocarcinomas of the liver (BDCC), which show a favorable prognosis. In contrast, MUC2 mucin (intestinal type secretory much detected by polyclonal antibody, anti‐MRP) was rarely expressed in IDC and ICC, whereas it was highly expressed in IPMT and BDCC. The results suggest that the differences in the expression of MUC1 and MUC2 mucins are a useful prognostic Indicator of mailgnancy potential in the neoplasms of the pancreas and intrahepatic bile duct. Moreover, the expression of MUC1 and MUC2 mucins was a useful Indicator of the malignancy potential of tumors derived from other organs, such as the ampulla of Vater, stomach and breast. In another study on the expression of several MUC1 much antigens with different patterns of glycosylatlon, sialylated‐MUC1 mucin detected by monoclonal antibody, MY. 1E12, was found to be expressed in all the Invasive carcinomas (IDC and ICC) but was not frequently seen in the non‐invasive type tumors (IPMT and BDCC), although the other types of MUC1 mucins did not show such contrast between the invasive and non‐invasive type turnors. The results suggest that sialylation of MUC1 mucin is associated with Invasive growth of neoplasms. In contrast, our study of the expression of MUC2 mRNA (transcript of intestinal type much) and MUC5AC mRNA (transcript of gastric type much) by in situ hybridization in the tumors of the pancreas and Intrahepatic bile duct found that the non‐Invasive type tumors (IPMT and BDCC) synthesize MUC2 mRNA and MUC5AC mRNA, whereas most of the Invasive carcinomas (IDC and ICC) do not. Furthermore, patients positive for MUC2 mRNA or MUC5AC mRNA expression in the tumors showed significantly better survival than the patients with no expression. The production of MUC2 or MUC5AC, an abundant extracellular intestinal or gastric type secretary much with high viscosity may be correlated, by a majority of the non‐Invasive type tumors, with the expansive growth of the tumors that display lower levels of invasion and metastasis.
Experimental ischemic liver injury and regeneration over 3 months: Histological observations in the rat
Authors: Manenti Antonio , Botticelli Laura , Pradelli John M. , Botticelli Annibale R.
Published: December 2008

Liver histopethology of segmental portal Ischemia occuring over a long‐term period has not been previously described. For these reasons histological changes In the rat liver were studied from 1 h to up to 90 days after a left lateral and middle segmental portal obstruction. Within 3 h, the hepatocytes showed glycogen depletion In Rappaport zones 1 and 2 and pericentral and central lobular congestion of sinusolds and veins, whereas within 3 days, vein thrombosis appeared in the center of the lobule and liver necrosis was observed in Rappaport zones 2 or 3 or both, followed by restitutio ad intergrum of the liver lobule morphology after 20–40 days. These results can be explained in light of two conditions occurring in the rat liver: (i) the pecullar low sensitivity of the liver to O2 debit and the protective or vasoactive effects used during hypoxia; and (11) the sinusoldal network as a collateral source of the hepatic vascular system. Therefore, morphologlcai assessment of this arteriolar and sinusoidal system, implicated in assuring efficient collateral blood supply in the rat liver with portal Ischemia, is essential for understanding the mechanisms behind a natural and timely repair of ischemic injuries in the human Iiver.
A histogenetic consideration of ovarian mucinous tumors based on an analysis of lesions associated with teratomas or Brenner tumors
Authors: Nomura Kouichi , Aizawa Shlgeo
Published: December 2008

To Investigate the histogenesis of ovarian mucinous tumors, clinicopathologic and histologic studies of mucinous tumors associated with teratomas or Brenner tumors were performed. Of 458 ovarian mucinous tumors, 13 (2.8%) and 8 (1.7%) were associated wlth teratomas or Brenner tumors, respectively. Of patients younger than 40 years, 5.1% had teratomas. Of patients 50 years or older, 3.5% had Brenner tumors. Histologically, nine lesions with teratomas and six lesions with Brenner tumors showed transitions or intimate admixtures of both eiements. The findings of the present study suggest that teratomas and Brenner tumors make small contributions to the histogenesis of ovarian mucinous tumors but may give rise to some mucinous tumors, especially in younger patients and older patients, respectively.
Ovarian endometrioid adenocarcinoma associated with steroidogenic foamy stromal cells
Authors: Kurihara Yuka , Kasahara Kyoko , Sasano Hironobu , Tsutsumi Yutaka
Published: December 2008

A case of a 69‐year‐old woman with endometriold adenocarcinoma of the ovary with functioning stromal cells is presented. The patient complained of genital bleeding. Endometrial curettage revealed endometrial hyperplasia. Preoperative levels of serum estradiol and progesterone were elevated, and serum gonadotropin levels were suppressed. The surgical specimen contained fist‐sired, bilateral, solid, ovarian tumors and a mildly enlarged uterus. Histologically, the proliferating, atypical, columnar cancer cells resembled early secretory, endometrial epithelial cells with subnuclear vacuolation, and there were clusters of fat‐laden foamy cells in the stroma. immunohistochemically, the cancer cells were positive for cytokeratin and progesterone receptor but negative for estrogen receptor. The stromal foamy cells were immunoreactive for vimentin, progesterone receptor, P450 side chain‐cleavage, 3β‐hydroxysteroid dehydrogenase, and adrenal 4‐binding protein. immunoreactivities of P450c‐17α hydroxylase and aromatase were only focally observed. These findings indicated that the stromal cells were steroldogenic and mainly produced progesterone. The cancer cells that expressed progesterone receptors showed morphologic changes in response to hormonal stimulation.
Immunohistochemical study of necrotizing lymphadenitis: A possible mechanism for apoptosis involving perforin and granzyme‐producing cytotoxic T cells
Authors: Mori Naoyoshi , Yatabe Yasushi , Asai Junpei , Nagasawa Toshiro
Published: December 2008

Twelve lymph node specimens with necrotizing lymphadenitis and which had florid necrotic lesions were studied immu‐nohistochemically. The majority of viable lymphoid cells in the necrotic foci were CD8+ lymphocytes and KP1+ or PGM1+ phagocytizing macrophages. The CD8+ T cells were Leu1+, Leu2+, Leu3‐‐, Leu4+, Leu5b+, Leu7‐‐, Leu11b‐ and Leu19‐‐, indicating a suppressor/cytotoxic T cell phenotype. In addition, the cytoplasm of these cells was immunoreactive for perforin and granzyme B in a granular pattern. With a nick end‐labeling technique, fragmented nuclei and some lymphoid cell nuclei were positively stained. These results suggest that the necrosis in necrotizing lymphadenitis is apoptotic necrosis of T cells targeted by CD8+, perform and granzyme‐producing, activated cytotoxic T cells, supporting a viral infection etiology.
An autopsy case of diffuse malignant mesothelioma of the pericardium
Authors: Sakuma Nobuo , Kamei Toshlakl , Unoki Tetsuhide , Okamura Hiroshi , Ishihara Tokuhiro
Published: December 2008

A report is presented of an autopsy case of a 71‐year‐old Japanoae man with a diffuse malignant epithelial mesothelioma of the pericardium with massive pericardlal effusion and a thickened perkardlum. He had no history of exposure to asbestos. He suffamd severe heart failure and later died. Autopsy revealed that tho tumor had developed over the pericardlum. Microscopically, the tumor cells were arranged In an epithelial form, and histochemically. the cytoplasm of these cells contained glycogen and hyaluronlc acid. The tumor tissue showed immunohlstochemical positivity for cytokeratin, epithelial membrane antigen, vimentln, cancer antigen 125, thrombomodulin. mesothellal antigen, muscle actin and human milk fat globule. In contrast, all the tumor cells were negative for human carcinoembryonic antigen and epithelial antigen. ultrastructurally. the tumor cells had long, thin microvilli, abundant lntermedlate filaments, intracyto‐plasmic lumina and long deamosomes. It Is considered that the patient had a typical malignant epithelial mesothelioma of the pericardium.
Carcinoma of the lung in Okinawa, Japan: With special reference to squamous cell carcinoma and squamous metaplasia
Authors: Nakazato Iwao , Hirayasu Tsuneo , Kamada Yoshihiko , Tsuhako Kyoko , Iwamasa Teruo
Published: December 2008

In Okinawa, a subtroplcal Island In southern Japan, squamous cell Carcinoma (SCC), especially the well‐differentiated form, Is prevalent, while this form is relatively rare in both the mainland and other countries (e.g. United States of America). More patlents with SCC from Okinawa, moreover, were positive for human papillomavlrus (HPV) DNA by polymerase chain reaction (PCR) (79%), and harbored HPV types 6, 16 and 18, In combination. On the other hand, less than 30% of the mainland patlents were positive for HPV DNA by PCR. Those patients who were positive all harbored only one HPV type. Furthermore, in Okinawa, there were a signiflcant number of cases with adenosquamous carcinoma, and they too were positive for HPV DNA. The SCC and the adenocarcinoma cells adjacent to the SCC component In these cases were also positive for HPV DNA, and such adenocarcinoma cells were enlarged In size with relatively wide cytoplasm. The authors postulate that HPV infects adenocarcinoma cells and changes them to enlarged cells, followed by squamous metaplasla. In this report, HPV DNA was transfected to adenocarclnoma cells (cultured cell fines) and this showed that HPV causes squamous metaplasla. In addition, aberrant expression of p53 was demonstrated In a large number of the SCC cases In Okinawa. The enlarged adenocarclnoma cells adiacent to the SCC components In adenosquamous carcinomas also showed aberrant expression of p53.The recent advances In the studies of anti‐oncogenes, p53, etc. and oncogenes are outlined. It Is to be noted that the molecular mechanisms of carcinogenesis in the lung have been studied In general, classifying lung tumors Into two groups, namely, small cell carcinoma (SCLC) and non‐small cell carcinoma (NSCLC). However, because human lung cancer is represented by a wide variety of histological types, molecular genetic studies according to a more detailed histological subclasslflcatlon is needed.
Giant cell tumor of bone: Frequent actin immunoreactivity in stromal tumor cells
Authors: Watanabe Kazuo , Tajino Takahiro , Kusakabe Takashi , Saitoh Atsuko , Suzuki Toshimitsu
Published: December 2008

Although giant cell tumor (GCT) of bone is a well‐recognized neoplasm with distinctive clinical and histopathological features, the origin of tumor cells, particularly of mononuclear cells, has not yet been established. An immunohistochemicai study was carried out on 11 cases of GCT of bone to examine the cellular natures of stromal mononuclear cells. In all cases, stromal cells were positive for muscle actin (HHF35) or α‐smooth muscle actin, and in eight of 11 cases, positivist was intense and extensive. The cell margin of osteoclast‐like giant cells (OGC) was stained positively by muscle actin, In addition to Intense and diffuse positive staining of the cytoplasm for KP1 (CD68), whereas α‐smooth muscle acting exhibited a negative reaction on the OGC. In conclusion, the tumor cells with muscle actin and α‐smooth muscle actin proclivities are not rare but frequently numerous In the GCT of bone; whereas further observation Is necessary to elucidate whether the stromal cells exhibit myoflbroblastlc cell differentiation exactly.
Modified formalin and methanol fixation methods for molecular biological and morphological analyses
Authors: Noguchi Masayuki , Furuya J Shuichiroh , Takeuchi Tomoyo , Hirohashi Setsuo
Published: December 2008

Several simplified fixation methods were examined to determine their suitability for both molecular biological analyses and morphological study. Fixation with 10% v/v formalin alone at 4°C and containing 5 mmol/L ethylenediamine‐N, N, N', N'‐tetraacetic acld (EDTA) at room temperature preserved significantly more high‐molecular‐weight DNA than 10% v/v formalin fixation at room temperature. The morphological differences between tissues fixed using these modified formalin fixation methods and conventional 10% v/v formalin fixation were negligible. Of the dehydration fixatives tested, 100% methanol did not cause regional differences due to artificial tissue shrinkage and the morphology of sections prepared by methanol fixation was preserved consistently better than that of acetone‐ or ethanol‐fixed sections. All three dehydration fixatives preserved relatively higher‐molecular‐weight DNA and RNA, compared with formalin. Cold formalin, formalin containing EDTA at room temperature and 100% methanol are recommended as standard and additional fixatives routine clinic pathological laboratory use.
Pulmonary hemorrhage and antiglomerular basement membrane antibody‐mediated glomerulonephritis after exposure to smoked cocaine (crack): A case report and review of the literature
Authors: M García‐Rostán y Pérez Ginesa , Bragado Federico García , MPuras Gi Ana
Published: December 2008

A case of Goodpasture's syndrome with a negative immunofluorescence examination of the lung biopsy in a 32‐year‐old man is described. The patient was a 40 clgarettes per day smoker, who had been smoking cocaine (crack) up to 3 weeks before hospital admission. He developed a diffuse alveolar hemorrhage with extremely acute respiratory distress, followed by renal failure with anuria. Transluguiar renal blopsy, Immunofluorescence and serum antiglomerular basement membrane antibody titer studies conflrmed the diagnosls of Goodpasture's syndrome without linear Jmmunogiobulln G deposlts as determined by Immunofluorescence examination of the alveolar basement membranes. The case Illustrates the potentially complex Interrelations between an autoimmune disease and exposure to substances with possible antigenic properties, besides the Imperative necessity for an early, accurate diagnosis and treatment for the potential for threatening life. Moreover, the association of Goodpasture's syndrome with crack has not been previously reported.
A case of lymphoid interstitial pneumonia in a 3‐month‐old boy not associated with HIV infection: Immunohistochemistry of lung biopsy specimens and serum transforming growth factor‐β1 assay
Authors: Koga Mayumi , Umemoto Yumi , Nishikawa Miki , Nakashima Kanae , Ishihara Tokuhiro , Furukawa Susumu
Published: December 2008

The case of a Smonthold boy with Iymphoid Interstitial pneumonia (LIP) is reported. He had cough and tachypnea, his weight gain was poor and a chest radiograph showed microgranular shadows in almost all lung areas. Histological Investigations revealed severe cellular Infiltration by a variety of Iymphoid and plasma cells with lymphoid follicle formation in the alveolar walls and also around the bronchioles. Foamy macrophages, a few lymphocytes and exudate filled the alveolar spaces. Epithellal cells lining the air spaces expressed human leukocyte antigen (HLA)‐DR. Lymphocytes and macrophages In the alveolar spaces expressed transforming growth factor (TGF)‐β strongly. Serum TGF‐β1 concentrations were measured eight times during the course of his Illness. They exceeded the upper end of the normal range In four samples and were with in it in the others. These results suggested that dysfunction of the Immune system, especially abnormal expression of HLA‐DR in non‐immune cells and exaggerated production of TGF‐β, played Important roles in the pathogenesis of LIP In this patient.
Genetic changes in prostate cancer
Authors: Konishi Noboru , Cho Niasaki , Yamamoto Kunichika , Hiasa Yoshio
Published: December 2008

Recent advances in molecular biology have allowed us to understand that it is the accumulation of genetic alterations which leads to each step of tumor genesis. What the specific alterations may be, however, often varies with each neoplasm. Prostate cancer is somewhat unique in its presentation to the pathologist of a bewildering array of histologies difficult to assign to diagnostic categories and contributing to misinterpretations of underlying molecular events. As with any malignancy, It is of utmost importance to thoroughly analyze and record the genetic aberrations found in prostate cancer with the objective of correlation to the pathology and natural history of the disease. Multiple ontogeny and tumor suppressor genes have been investigated in both clinical and latent cancers using conventional mutational analyses. To probe deeper Into these genes and to uncover novel molecular events, genomic tumor DNA were examined using restriction landmark genomic scanning (RLGS), a method which allows the Identification and comparison of specific genetic alterations within large segments and multiple samples of DNA at a time. This article reviews what has been identified based on numerous molecular studies, focusing on the genetic alterations peculiar to human prostate cancer.
Bile canaliculi‐like lumina in fibrolamellar carcinoma of the liver: A light‐ and electron‐microscopic study and three‐dimensional examination of serial sections
Authors: Sato Shin‐ichiro , Masuda Tomoyuki , Oikawa Hiroki , Satodate Ryoichi , Suzuki Kazuyuki , Sato Shunichi , Suzuki Akihiko , Monma Nobuhiro
Published: December 2008

Flbrolamellar carclnoma (FLC) Is a varlant of hepatocellular carcinoma characterlzed by dlstlnct pathologicel features. The presence of Intracellular lumlna resembling blle canalicull was previously reported in tumor cells of FLC on electron microscopy. Using light microscopy, we describe the presence of intracellular lumina In FLC, which was resected from a 15‐year‐old Japanese girl, as round structures lined with a brush‐like border. These lumina occasionally contained blle. Light microscopic examination of 1 μm thick serial sections of Eponembedded tissue samples showed that the lumina were located in the intracellular space without any connection to the Intercellular space. However, we also detected a small number of lumlna that were lined by microville which were present between adjacent tumor cells. Results suggest that the presence of the Intracellular Iumlna in tumor cells probably represents a common histopathologic feature of FLC.
Morphogenesis and development of superficial spreading tumor of the colon and rectum
Authors: Yasuda Kazuhiro , Ajioka Yoichi , Watanabe Hidenobu , Matsuda Keiji , Kitand Seigo
Published: December 2008

The aim of this study was to clarify the morphogenesls and mechanism of a wide Intramucosal extension of a superficial Spreading (eplthelial) tumor (SST; defined as an epithelial tumor with wide Intramucosai spreading Involving a diameter of 30 mm or more) In the colon and rectum. For this purpose favorable sites, histoiogical components, and hlstological growth patterns were compared between 95 cases of SST (16 adenomas and 79 carclnomas) and 2356 non‐SST cases, which served as controls. The frequency of SST was slgnificantly hlgher In the cecum and rectum, and lower In the sigmold colon when compared to the locations of the control. Among the SST cases, 82.3% of superficial spreadlng carcinoma (SSC) had an adenomatous component and 96.2% had a cytologically low‐grade carcinoma (CAL). In intramucosal SSC, the adenomatous and/or CAL component was predomlnant, and the proportion of high‐grade carclnoma (CAH) was significantly smaller In Intramucosal SSC In comparison with the control group. In the mucosal spreading area of SST, 78.9% were tubulovillous In histological type and 86.3% showed a replacing growth pattern. These results indicate that an SST inhially develops as an adenoma in at least 85.3% of cases and CAL in 14.7% cases at most; spreads superficially in the mucosa by a replacing growth mechanism that forms a tubulovillous and villous structure; and is affected by Intestinal peristalsis less than non‐SST.
Numerous eosinophilic globules (skeinoid fibers) in a duodenal stromal tumor: An exceptional case showing smooth muscle differentiation
Authors: Matsukuma Susumu , Doi Masateru , Suzuki Masatoshi , Ikegawa Kazuya , Sato Kimiya , Kuwabara Noriyuki
Published: December 2008

A unique case of duodenal stromal tumor In a 51‐year‐old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of tangled 45 nm thick fibrils, which were ultrastructurally Identical to ‘skelnoid fibers’. The presence of glycogen granules in the tumor cells and the Immunoreactivity for α‐smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultra‐structural features indicating neural differentiation. In previous studies, the presence of such ‘skeinoid fibers’ was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings In the present case suggest that numerous ‘skeinoid fibers’ can be Identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.
Epstein‐Barr virus‐related Hodgkin's disease showing B cell lineage in an immunosuppressive patient seropositive for HTLV‐I
Authors: Murata Tetsuya , Nakamura Shigeo , Kato Hiroya , Yatabe Yasushi , Shiraishi Taizo , Kuroda Makoto , Yatani Ryulchi , Suchi Taizan
Published: December 2008

A case of Hodgkln's disease (HD), lymphocyte depression (LD) type In an Immunosuppressive patient is described. The patient was a 48‐year‐old male and his parents were born In the Kyushu area, which is an endemic area for adult T cell lymphomaheukemla (ATL). He was seropositive for ATL virus (ATLV, also referred to as HTLV‐I) and showed a marked Immunosuppressive condition. He developed LD‐HD and Pneumocystis carinii pneumonia, and died due to respiratory failure. The Immunohistochemical and in situ hybridization analyses revealed that the Reed‐Sternberglike cells In the lymph node biopsy sample were positive for Ber‐H2 (CD30), Leu‐M1 (CD15), L‐26 (CD20), Bcl‐2, p53 and EBER, the viral genome of Epstein‐Barr virus (EBV).
Mutations of the X region of hepatitis B virus and their clinical implications
Authors: Uchida Toshikazu , Saltoh Takafumi , Shinzawa Haruhlde
Published: December 2008

Nucleotide (nt) sequences of the X region of more than 130 hepatitis B virus (HBV) Isolates were determined and derived from patients with a variety of clinical features. Correlation of not substitutions with clinicopathological characteristies was attempted. The X region (465nt) Is crucial for the replication and expression of HBV because the X protein trans‐activates the HBV genes and this region contains the core promoter, enhancer II, and two direct repeats. There are several mutational hotspots, some of which seem to relate to immunological epitopes of the X protein. Two kinds of mutations which have important clinical significances were found. One is an 8‐nt deletion between nt 1770 and 1777, which truncates 20 amino acids from the carboxyl terminus of the X protein. This deletion leads to the suppression of replication and expression of HBV DNA, resulting In immunoserological marker (HBsAg) negativity. This silent HBV infection Is responsible for the majority of non A to non‐E hepatitis. The other mutation substituting T for C (nt 1655), T for A (nt 1764) and A for G (nt 1766) seems to relate to fulminant hepatitis. Further sequencing studies and In vitro mutagenesis experiments will clarify the significance of other mutations of the X region.
Histological grading and staging of IgA nephropathy
Authors: Shigematsu Hidekant
Published: December 2008

More than 25 years have passed since immunoglobulln A (IgA) nephropathy was introduced as a disease entity inde pendent of glomerulonephritis. it has been known that more than 30% of cases have gona into end‐stage renal fallure within 20 years, indicating the presence of a chornic active group in this disease. Histologicaily this disesase is com posed of at least three types of tissue damage:(1) minimal inflammation including deposition of IgA‐containing sub stances with minor matriclal increase; (II) acute lesions char acterized by matricial damsge of glomerular basement membrane (membranolysis) and/or mesangial matrix (mes anglolysis) with inflammstory cell accumulation and/or intrinsic cell proliferation; and (III) chronic lesions mainly composed of postinfiammstory sclerosis. The progression is actually accelerated by the frequency of acute lesions, resuiting in increased glomerular scierosis focl. In such a situation, the histologic grading and stagi (G‐S)system is proposed, with the aim of having a more preclse understanding of the disease prosses. The histological grade (G) is estimated by the extent of acute giomerular and tubulointer stitial lesions, and the stage (S) is evaluated by the increase of extracellular matrices of the glomerull and inerstitial fibrosis. The evaluation of G and S is expressed semiquanti tativety for more helpful clinical use.
c‐myc, c‐erbB‐1 and c‐erbB‐2 expressions in urothelial carcinoma
Authors: Onodera Takafumi , Hashlmoto Yasuhlro , Yaglhashi Soroku
Published: December 2008

The expression of c‐myc, c‐erbB‐1 and c‐erbB‐2 In 24 cases of urothelial carcinoma by Southern and northern blot analysis, and immunohistochemistry was examined. The results were compared with the pathological grade and stage. We found elevated mRNA expressions of c‐myc and c‐erbB‐1 In 19 and 11 of 21 cases, respectively, but there was no apparent amplification or rearrangement of these oncogenes in any of the cases examined. By immunohistochemistry using anti‐epidermal growth factor receptor antibody, most of the cases showed positbe immunoreactivity on the cancer cell membranes, and cancers of higher pathological grade and stage showed more intense staining. By contrast, amplification of c‐erbB‐2 was detected in four of 24 cases, all of which were assigned to a high pathological grade (G3). Elevated c‐erbB‐2 mRNA levels appeared to correlate with the pathological grade of the cancers. Positive immunohistochemical reactions to c‐erbB‐2 were found in the cancer cell membranes in three of 24 cases, which were accompanied by amplification and eievated mRNA levels of c‐erbB‐2. In conclusion, expressions of c‐myc, c‐erbB‐1 and c‐erbB‐2 were all elevated in the majority of urothellal carcinomas, but the amplification was not universal.
Epstein‐Barr virus‐infected lymphocytes in non‐neoplastic lymph nodes of patients infected with human immunodeficiency virus
Authors: Zheng Heng , Mori Shigeo
Published: December 2008

Non‐Hodgkin's lymphomas occurring In AIDS patients (AIDS NHL) are known to be highly associated with Epstein‐Barr virus (EBV). However, there have been no previous detailed studies of the distribution of EBV‐Infected non‐neoplastic lymphoblasts, which may act as precursors of AIDS‐NHL In the present study, an attempt was made to detect such EBV‐Infected cells in patients' lymphoid organs. Fifteen non‐neoplastic lymph nodes obtained from HIV‐positive individuals were processed for in situ demonstration of EBV‐encoded small RNA (EBER‐1) and EBVencoded latent membrane proteln 1 (LMP‐1). An Increased number of EBER‐1–expressing cells were observed (9/15). EBER‐1–positive cells were present much more frequently in advanced cases, as evaluated using the histopathologic criteria of Grund‐mann (1/6 cases showing irregular follicular hyperplasia; 3/4 showing the beginning follicular destruction; 2/2 showing progressive follicular destruction; 3/3 showing follicular involution). LMP‐1 was detected in 3/9 EBER‐1–positive cases, and all three of these cases were at the most advanced stage. Furthermore, cells expressing LMP‐1 were larger (62.83±6 μm2) than EBER‐1 + LMP‐1‐‐ cells (29.05±7 μm2). These results indicate that cells with latent expression of the EBV gene increase in number in lymphoid organs of HIV‐infected individuals at an advanced stage and that some of the cells are in a transformed state. It is possible to speculate that these cells are precursors of AIDS‐NHL
Chromosomal translocations in human soft tissue sarcomas by interphase fluorescence in situ hybridization
Authors: Yoshlda Haruhlko , Nagao Katsuhtto , Ito Hlsao , Yamamoto Kichizo , Ushigome Shinlchiro
Published: December 2008

In soft tissue sarcomes, clonal rearrangement of chromosomes has been shown by cytogenetic analysls to be unique and specific for tumor types. The development of fluorescence in situ hybridbation (FISH) has allowed detection of chromosomal rearrangements In the interphase nuclel isolated from paraffin‐embedded tissues. Three kinds of trans‐locations in the interphase nuclel that were isolated from 47 cases of soft tissue sarcomas ware examined by FISH with chromosome‐speclfic DNA probes of centromeric and total probes. of 47 soft tissue sarcomas 42 (89.4%) revealed tumor‐specitic transiocations by retrospective cytogenetic analysis. Transiocation t(X;18) was detected In 25/28 synovial sarcomas; translocation t(11;22) In 5/6 Ewlng's sarcomas and primitive neuroectodermal tumors (PNET); and translocation t(12;16) was found in 12/13 liposarcomas, including 10 myxold and two round cell lypes as clonal chromosomal aberrations specific for both subtypes. Based on the cytogenetic analysis, Ewing's sarcoma is related closely with PNET as shown by MIC2–protein reactivity. Other cytogenetic findings of translocation t(12;16) Indicate that round cell liposarcomas share chromosomal changes with myxoid lipo sarcomas, and further suggest that both tumor subtypes of liposarcoma may possess common precursor cells. FISH is a useful aid in determining the tumor type of soft tissue sarcomas with regard to histogenetic origin.
Small cell carcinoma of the ovary: A case report of large cell variant
Authors: Fukunaga Masaharu , Endo Yasuhiko , Nomura Kouichi , Ushigome Shinchiro
Published: December 2008

An extremely rare case of large cell variant of ovarian small cell carcinoma is described. A 34‐year‐old woman (gravid 1. para 1) had a unilateral ovarian mass measuring 17 cm in great at diameter and a metastasis lesion in the omentum. Microscopically, the tumor showed a diffuse arrangement of large, closely packed epithelial cells with abundant eosino‐philic cytoplasm and large nuclei with prominent nucleoli. The tumor cells also were arranged in follicle‐like and trabe‐cular structures and cords. Immunohlstochemically, many tumor cells were diffusely positive for epithelial membrane antigen and some cells contained cytokeratin CAM5.2, valentine, neurofiiament, neuron‐specific enoiase, or alpha‐1 antitrypsn. However, no specific IIneage was detected. The tumor was aneuploid by flow cytometry. The patient received chemotherapy postoperatively. However, the patient showed metastases in the Inguinal and retruperitoneal lymph nodes. The aerum calcium level, which was not measured preoperatively, was mildly elevated postoperatively. The patient was well with no evidence of disease 17 months after diagnosis. This tumor must be distinguished from other primary or metelltatic ‘undifferentiated’ neoplasms, especially ovarian small cell carcinoma of pulmonary type and granulosa cell tumor.
A case of sarcomatoid carcinoma of the thymus
Authors: Nishimura Mitsuyo , Kodama Tetsuro , Nishiyama Hiroyuki , Nishiwaki Yutaka , Yokose Tomoyuki , Shimosato Yukio
Published: December 2008

A 57‐year‐old woman presented with a 10×10 cm anterior mediations mass. The tumor had Invaded the pericardium, both lungs and the left brachiocephallc vein, and was treated by partial resection and postoperative radiation therapy. Pathological examination of the tumor revealed squamous cell carcinoma with a spindle cell sarcomatous component. Immunohistochemically, keratin and epithelial membrane antlgen were posltive In both the spindle cell sarcomatous areas and the squamous cell carcinomatous area and thus, a diagnosis of thymic carcinoma of sarcomatoid type was made. The patient died of recurrent disease 1 year after surgery. This case is the seventh reported In the English literature Because of the poor outcome, adjuvant therapy is recommended.
Monoclonal antibodies against mouse splenic stromal cells
Authors: Ito Masafumi , Nakayama Atsuo , Ohbayashi Masaharu , Nakagawa Atsuko , Kasai Kenji , Fujino Masahiko , Asai Junpei
Published: December 2008

A panel of rat monoclonal antibodies directed against mouse splenic stromal cells were isolated. These monoclonal antibodies were Immunohistochemically divided into four groups which reacted with non‐lymphoid cells of the murine spleen; (1) in the white pulp, (11) at the marginal zone, (111) in the red pulp, and (IV) on the endothelium of splenic blood vessels. These monoclonal antibodies were studied Immunohistochemically In lymphoid organs by means of light and electron microscopy. Monoclonal antibodies SS‐4 (group I) reacted with fibroblastic reticulum cells that were distributed only in the white pulp of the spleen and In the follicular areas of lymph nodes. The SS‐4 staining cell, In clustered splenic stromal cells, formed colonies which Included a small number of Thy‐1 positive lymphocytes. Therefore, we concluded that SS4 staining stromal cells comprise the lymphoid cornpartment. In contrast, monoclonal antibodies SS‐1, SS‐3 and SS‐5 (group II) reacted with dendritic shaped cells in the marginal zone of the spleen. Examination of splenic extra‐medullary hematopolesis in mice rescued by bone marrow transplantation after lethal irradiation revealed that SS‐3 and SS‐5 reacted with dendritic shaped stromal cells in clonal nodules of engrafted marrow in the red pulp. SS‐3 and SS‐5 staining cells could not be observed in physiologic hematopoiesis of non‐transplanted mice. It was suggested that SS3 and SS‐5 staining stromal cells are Involved in primitive hematopoiesls. Monoclonal antibodies SS2, SS‐6 and SS‐7 (group 111) mainly reacted with dendritic cells and macro‐phages in the red pulp. Monoclonal antibodies SS‐8 and SS‐9 (group IV) reacted with endothelial cells of blood vessels and sinuses. These findings of heterogeneity in mouse splenic stromal cells are further evidence that specific micro‐envlronments are composed by speclalired stromal cells.
Contribution of cell proliferative activity to malignancy potential in testicular seminoma
Authors: Hori Kazutoshl , Uematsu Kunio , Yasoshima Hitoshi , Sakurai Kazunari , Yamada Aklhiko
Published: December 2008

Testicular anaplastic seminoma, which has a high mitotic activtiy, is regarded aa more malignant than typical seminoma, although its prognosis is still unclear. To determine whether seminoma with relativety greater malignancy potential can be ldentified based on the cell proliferative activity, the mitotic rate (MR; mitotic count per high‐power field), mitotic Index (MI; mitotic count per 1000 cells), Ki‐67 labeling Index (K1–67 LI; the percentage of positive cells) and prolifereting cell nuclear antigen LI (PCNA LI; the percentage of positive cells) were histologically examined In 44 patients. The MI, Kl‐67 LI and PCNA LI In patients with metastatlc disease were signmeantly higher than those in patients without metastatic disease, and the MI In patients with fatal disease was signmcantly higher than those in patients cured of the disease. However, these distributions of the MI, K1–67 LI and PCNA LI values overiapped for both pairs of groups. There were no significant differences in the YR. These results suggest that the cell proliferatbe activity makes a small contribution to the malignancy potential in testicular seminoma, with the activity being not necessarily indicative of metastasis and prognosis.
Comparative morphometric study of immunohistochemical versus conventional staining for the evaluation of megakaryocytopoiesis in normal and pathological bone marrow biopsies
Authors: Marisavijević Dragomir , Radoševič‐Radojkovič Nina , Rolovič Zoran
Published: December 2008

ldentification of megakatyocytes by immunohistochemistry may be superior to hematoxylin‐eosin (HE) stain method for assessing megakaryocyte size and number In clinical specimens; however, a sidsby‐side comparison of the two methods has not been reported. In the present study, comparative morphometry using both methods was performed on marrow biopsies of normal individuals, and of patients with myela‐dysplastic syndrome, chronic myeloid leukemia and Immune thrombocytopenia. Morphometrlc results In the present study showed that precise megakaryocyte size can be calculated in normal and pathologic bone marrow sections by using HE stain if one employs stereological corrections. In contrast, megakaryocyte numbers can be more precisely detected by immunohistochemistry than by HE stain, particularly In myelodyspiastic syndrome and chronic myeloid leukemia. Differentiation disturbances and ineffective megakaryocytopolesls In myelodysplastic syndrome were demonstrated by immunomorphometric analyses.