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Pathol Int

Hyperplastic foci in chronic liver disease: their proliferative activity assessed by nucleolar organizing region.

Year 1998
Wakasa K. Haba T. Sasaki M. Sakurai M. Ikebe T. Shuto T. Hirohashi K. Kinoshita H.
Department of Pathology, Osaka City University Hospital, Japan. wakasa@msic.med.osaka-cu.ac.jp
In the cirrhotic and precirrhotic liver, there may be small foci with increased cellularity and amphophilic cytoplasm. These are microscopic lesions that do not form macroscopically detectable nodules, which differ from the macroscopically apparent nodules of dysplastic nodules. In the present study, we assessed the proliferating activity of 12 hyperplastic foci in 11 patients with cirrhosis or chronic hepatitis, by staining for agyrophilic nucleolar organizing regions (AgNOR). The mean AgNOR count per nucleus in the hyperplastic foci ranged from 0.96 to 1.36 (mean, 1.13; SD 0.12), and from 0.81 to 1.06 (mean, 0.94; SD 0.08) in the controls. The AgNOR count in the hyperplastic foci was significantly higher than that in the controls (P < 0.01). Small hyperplastic foci show increased proliferative activity. Further study on these foci is required to clarify their relation to hepatocarcinogenesis.

Analysis of K-ras oncogene mutation directly applied to atypical cell clusters on cytologic smear slides of bile and pancreatic juice.

Year 1998
Fukushima N. Suzuki M. Fukayama M.
Department of Diagnostic Pathology, Nippon Telegraph Corporation (NTT) Kanto Teishin Hospital, Tokyo, Japan. nrfukush@gan2.ncc.go.jp
To develop an objective reference for the cytological evaluation of atypical cells in bile and pancreatic juice, we analyzed K-ras oncogene mutation in atypical cell clusters, which were collected directly from cytological smear slides; 50 samples (cell clusters) from 31 smear slides of 21 patients with carcinomas of the pancreatic head region, and nine samples from eight cases of benign disease. These cell clusters (5-1000 cells/cluster) were selectively suspended in buffer containing proteinase K, and subjected to DNA extraction. K-ras codon 12 mutation was determined by polymerase chain reaction amplification, followed by digestion with BstNI. The K-ras gene was amplified in 20 of 21 cases with carcinoma (34/50 samples), and in seven of eight cases with non-neoplastic disease (8/9 samples). Among the cases of which primary tumors showed K-ras mutation, amplification was successful in 10 of 11 cases; mutation was demonstrated in three of seven cases with cytologically atypical cells (4/11 samples), and in three of three cases with cytologically malignant cells (5/7 samples). No mutation was identified in the 10 cases of carcinoma without K-ras mutation (0/15 samples), or in eight cases of non-neoplastic disease (0/8 samples). Cytological details could be comparatively evaluated between atypical cell clusters with or without mutation on the same smear slides in two cases. This type of direct analysis of atypical cell clusters may be useful in the self-assessment of cytological diagnosis of bile and pancreatic juice.

The first reported case of intestinal spirochaetosis in Japan.

Year 1998
Nakamura S. Kuroda T. Sugai T. Ono S. Yoshida T. Akasaka I. Nakashima F. Sasou S.
Division of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan. nakamurashin@jsn.justnet.or.jp
A 65-year-old Japanese male consulted Ozuchi Prefectural Hospital (Iwate, Japan) on 19 January 1994 complaining of weight loss. Cecal mucosal biopsy material, which was stained with hematoxylin-eosin revealed a thick, basophilic fuzzy fringe covering the surface epithelium. Transmission and scanning electron microscopy observations demonstrated the presence of slightly wavy spirochaetes with tapered ends, which were attached to the surface epithelium of the colonic mucosa via one of these ends. The patient did not display any clinical symptoms of inflammatory bowel disease, and laboratory tests eliminated an immunodeficiency condition. Thus, in the present case, the intestinal spirochaetes appear to be harmless commensals. This paper presents the first reported case of intestinal spirochaetosis in Japan.

Immunohistochemical analysis of TrkA neurotrophin receptor expression in human non-neuronal carcinomas.

Year 1998
Koizumi H. Morita M. Mikami S. Shibayama E. Uchikoshi T.
Second Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan. hiro@marianna-u.ac.jp
The Trk family of tyrosine protein kinase receptors plays a significant role in the development and maintenance of neural tissues. It has been recently shown that Trk receptors are also expressed by a wide range of normal non-neuronal tissues in humans in a cell type-specific manner. In the present study, the expression patterns of TrkA in 337 non-neuronal invasive carcinomas of 15 different human tissues were investigated immunohistochemically. Overall, 133 (39%), 101 (30%) and 103 (31%) tumors exhibited strong, moderate and no TrkA immunoreactivity, respectively. Esophageal and thyroid carcinomas expressed high levels of TrkA, whereas the levels in gastric and colon cancers were low. TrkA expression was detected not only in carcinomas originating from TrkA-positive normal counterpart tissues, including the esophagus, breast, lung and uterus, but also in those from TrkA-negative tissues/cells of the thyroid, liver and ovary. Immunostaining for nerve growth factor-beta, the specific ligand for TrkA, in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells. These results suggest that paracrine/autocrine regulation via stromal/tumoral NGF-tumoral TrkA interaction may be involved in the growth of certain non-neuronal carcinomas.

Genetic alterations in a patient with Turcots syndrome.

Year 1998
Suzui M. Yoshimi N. Hara A. Morishita Y. Tanaka T. Mori H.
First Department of Pathology, Gifu University School of Medicine, Japan.
Turcot's syndrome (TS) is a rare disorder associated with the development of both brain and colon neoplasms. Because of the very low incidence of the disease, its molecular basis remains unclear. Presented is a TS case of a 30-year-old Japanese male with a histopathologically confirmed diagnosis of both brain tumor (glioblastoma multiforme) and colon tumor (well-differentiated adenocarcinoma). Germline mutations of the p53 gene, somatic mutations of the Ki-ras, p53 and APC genes, and microsatellite instability (MSI) was examined using polymerase chain reaction (PCR)-single strand conformation polymorphism analysis, followed by PCR-direct sequencing, and sequencing after subcloning. No germline mutations of the p53 gene were found. Somatic mutations of Ki-ras and APC genes were found in the colon adenocarcinoma but not in the brain tumor. No somatic mutation of the p53 gene was present in either colon or brain tumors. Microsatellite instability of both colon and brain tumors was positive in two of four loci. These results indicate that the colon tumor of the TS patient carries the Ki-ras and APC gene mutations. The finding of MSI in both the brain and the colon tumors may support the hypothesis that alterations of DNA repair genes are involved in the tumor development of the TS patient.

Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype.

Year 1998
Yasumi K. Guo RJ. Hanai H. Arai H. Kaneko E. Konno H. Takenoshita S. Hagiwara K. Sugimura H.
First Department of Pathology, Hamamatsu University School of Medicine, Japan.
A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.

Prediction of efficacy of interferon treatment of chronic hepatitis C by multivariate analysis and a new classification.

Year 1998
Kim SR. Hayashi Y. Yoon S. Taniguchi M. Yang MK. Kim KI. Kim MM. Saeki K. Nukata I. Imoto S.
Department of Gastroenterology, Kobe Asahi Hospital, Japan.
One hundred and fifteen patients with chronic hepatitis C were administered interferon (IFN) and classed into two groups: (i) complete responders (CR), HCV-RNA continuously negative 1 year after treatment; and (ii) non-responders (NR), positive 1 year after treatment. Multivariate analysis comprised eight variables: age, sex, transfusion history, alanine aminotransferase level, viral genotype, level of viremia, type of IFN, and total amount of IFN. The HCV-RNA level was correlated with complete response (P = 0.0175). Liver biopsy specimens were classified into four grades and stages according to the measure of severity and the extent of fibrosis, respectively. There was no correlation between the efficacy rate and grading. However, in staging there was a difference in the efficacy of IFN between stages 1 or 2, and stage 3 (0.05 < P < 0.1 and 0.01 < P < 0.025, respectively). Of the CR patients, 0% (0/5) were at stage 0 (no fibrosis); 27.5% (22/80) at stage 1 (mild); 42.9% (6/14) at stage 2 (moderate); and 6.3% (1/16) at stage 3 (severe fibrosis). Thus the new classification would be useful in predicting roughly the efficacy of IFN.

Primary hepatic malignant fibrous histiocytoma: report of a case and review of the literature.

Year 1998
Fujita S. Lauwers GY.
Department of Pathology and Laboratory Medicine, College of Medicine, University of Florida, Gainesville 32603-0275, USA.
Malignant fibrous histiocytoma (MFH) is a common sarcoma of adulthood, frequently arising in the extremities, but also in the abdomen and the retroperitoneum. Primary MFH of the liver, however, remains extremely rare and is one of the least diagnosed primary hepatic sarcoma. Another case of primary MFH of the liver is reported. The patient presented with a 12 cm mass involving the right and left lobes of the liver. The histopathologic examination revealed a typical MFH swirling (storiform) pattern composed of atypical spindle and giant cells. The radiologic, histologic, and clinical behavior of this rare neoplasm are reviewed.

Gastric metastasis from breast cancer: a pitfall in gastric biopsy specimens.

Year 1998
Shimizu M. Matsumoto T. Hirokawa M. Shimozuma K. Manabe T.
No information.
A 49-year-old woman presented with abdominal discomfort and weight loss. Gastroduodenoscopy showed small polypoid lesions and biopsy specimens suggested primary adenocarcinoma with neuroendocrine differentiation. As the patient had a prior history of metachronous breast cancer, it was concluded that the case was metastatic carcinoma from the breast. The usefulness of a panel of selected immunohistochemical markers to determine the primary site of the breast in an appropriate clinical setting is greatly emphasized.

Localized accumulation of Russell body-containing plasma cells in gastric mucosa with Helicobacter pylori infection: Russell body gastritis.

Year 1998
Tazawa K. Tsutsumi Y.
No information.
One of the gastric biopsy specimens taken from a 53-year-old male showed localized accumulation of plasma cells containing Russell bodies, in association with infection of Helicobacter pylori (H. pylori). An endoscopic study demonstrated multiple ulcer scars in the antrum. Immunohistochemically, H. pylori infection was identified both on the surface of the foveolar epithelial cells and in the cytoplasm of macrophages in the lamina propria mucosae. Plasma cells filled with 'Russell bodies', so-called 'Motts cells', were immunoreactive for CD45, CD79a and IgG. This seems to be a previously unrecognized tissue reaction in gastric mucosa associated with H. pylori infection, which we have called 'Russell body gastritis'.

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