Journal of Pathology and Translational Medicine

Volume 28(6); December 1994

Original Articles

An Ultrastructural Study on the Small Intestinal Absorptive Cells of Rat after Administration of Lead Acetate.: Dong Sug Kim, Kee Kwon Kim, Eun Sook Chang; Korean J Pathol. 1994;28(6):559-568.

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Abstract PDF: This study was carried out to visualize lead by Timm sulphide silver method and to define lead-induced change of duodenal absorptive cells of rat after administration of 0.01% lead acetate with drinking water. Sprague-Dawley rats, weighing 250g, were used, and they were orally administered with 0.01% sodium acetate and sacrificed at 0.5, 1, 1.5 hours and 2, 7, 15, 30, 45, 60 days after administration. A portion of duodenal tissue was observed under light microscope, scanning and transmission electron microscopes after development with Danscher method. The blood lead concentration in experimental group began to increase from the 2nd day after administration, and it increased gradually until the 45th day and decreased at the 60th day. On light microscope, many brown lead granules were observed at the villi tip at the 2nd day. There is mild blunting of villi tip at the 45th day. At the 60th day, most of the villi were mildly shortened and showed lymphangiectasia. On scanning electron microscope, the villi tip was mildly blunted and the extrusion zone became irregular at the 45th day. The depth of creases did not change. At the 60th day, the villi tip was moderately blunted and the extrusion zone was markedly irregular. The depth of creases increased. On transmission electron microscope, at 0.5 hour after oral administration, numerous lead granules were diffusely scattered and were not confined to any specific microorganelles. The lead granules decreased with time. At the 7th 15th day, the intercellular spaces were widened and several vacuoles appeared and the condensation of mitochondrial matrix. There was also ribosomal detachment from RER, and there was neither secondary lysosomes or post-lysosomes. At the 30th and 45th day, secondary lysosomes appeared and the condensation of mitochondrial matrix with early formation of myelin figures was noted. At the 60th day, the intercellular space widening extended to the upper most portion of the cells, and nonspeciqic degenerative changes became severe. In view of above mentioned findings, it can be concluded that passive diffusion as well as active transport was partly involved in the absorption of lead. Most of the changes of microorganelle are compatible with nonspecific degenerative changes which could occur due to impairment of oxidative phosphorylation.

Short-term Effect of Iron on the Hyperplastic Lesions of Chemical Hepatocarcinogenesis.: Young Nyun Park, Woo Hee Jung, Soon Hee Jung, Chan Il Park; Korean J Pathol. 1994;28(6):569-583.

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Abstract PDF: This study was undertaken to elucidate the short-term effect of iron on the hyperplastic lesions of experimental hepatocarcinogenesis. The Solt-Farber's resistant hepatocyte model was chosen for the experiment, and Sprague-Dawley rats wee divided into six groups: normal control, iron-rich diet administration with or without hydroxyquinoline. The iron content, microscopic changes, bromodeoxyuridine(BrdU) labelling index and the DNA polidy were studied. In the carcinogen administered group, oval cell proliferation and consecutive hyperplastic lesions of hepatocyte developed regardless of iron administration. The hepatic iron content was increased rimarkably by iron administration, but gradually decreased as the hyperplastic lesions developed in carcinogen administered groups. Although the administration of iron without carcinogen induced hepatic accumulation of stainable iron, the hyperplastic lesions appeared to be lack of it. BrdU labelling indices of the oval cells and the hyperplastic lesions of hepatocyte were very high and were not significantly altered by iron administration. Most liver cells had diploid or tetraploid DNA content, but there was an increase of diploidy as the development of hyperplastic lesions regardless of iron administration. The results indicate that the chemical carcinogen-induced hyperplastic lesions of hepatocyte do not accumulate iron, and that short-term iron administration does not affect the development of hyperplastic lesions and their proliferative activity and DNA ploidy.

Expression of BrdU and C-Ha-ras in Experimentally Induced Enzyme Altered Foci of the Liver and Hepatocellular Carcinoma.: Myung Sook Kim, Woo Ho Kim, Yong Il Kim; Korean J Pathol. 1994;28(6):584-595.

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Abstract PDF: For sequential phenotypic changes including enzyme altered hepatocytic foci, hyperplastic nodules, hepatocellular adenomas and carcinomas were produced in Sprague-Dawley rats by Solt-Farber method (administration of diethylnitrosamine and acetylaminofluorene (AAF), and partial hepatectomy). The immunohistochemical expressions of glutathione S transferase P (GST-P) and bromodeoxyuridine (BrdU) were assessed for selective proliferative activity in the enzyme altered foci and the subsequently developed lesions by double immunohistochemical staining technique. Immunoreactive areas against GSTP gradually increase from early period of carciogenesis. BrdU labeling in such areas remained high during the first week. but decreased thereafter. BrdU labeling index remained low in the GSTP negative area throughout the experimental period. This suggests that cells in the enzyme altered foci keep away from the suppressor effect of AAF in contrast to the normal cells in which their growth are inhibited by AAF. BrdU labeling index remained very low in both hyperplastic nodule and adenoma which were prevalent during the mid-experimental period, but increase markedly in carcinoma. The long period of low BrdU labeling index seems to correspond to the "slowly growing step of persistent nodule" during hepatocarcinogenesis. The differentiation index, a ratio of S phase fraction between GSTP positive and negative areas, was low in adenoma-developing period and high in carcinoma-developing period. C-Ha-ras p21 was not expressed in foci of enzyme altered hepatocyte and hyperplasia, but highly positive in carcinoma. This indicates that the c-Ha-ras may involve the late step of hepatocarcinogenesis.

Craniofacial Morphogenesis of Mouse with Trisomy 16.: Jung Sun Kim, Jeong Wook Seo, Suk Wha Kim, Je G Chi; Korean J Pathol. 1994;28(6):596-604.

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Abstract PDF: Based on the genetic homology between mouse chromosome 16 and human chromosome 21, experimentally induced trisomy 16 mouse has been considered to serve as a suitable model for human Down syndrome. Mice with trisomy 16 express several phenotypic characteristics of human trisomy 21 syndrome; i.e., intrauterine growth retardation, anarsarca, congenital heart disease, brain abnormality, etc. To elucidate morphogenesis of characteristic craniofacial malformation in human Down syndrome, we studied trisomy 16 mouse fetuses that were produced by crossing karyotypically normal C57BL/6 female ice with males carrying the two Robertsonian translocation chromosome Rb(16.17)/Rb(11.16). We examined a series of trisomy 16 conecptuses and their normal littermate controls from day 14 to day 18 of gestation by gross observation and serial microscopic sections. In addition to smaller size and generalized edema, we observed variable, but definite delay in brain and craniofacial development in trisomy 16 mice. The brain revealed less stratified telencephalon, underdeveloped thalamus and hypothalmus with relatively wide third ventricle, and small rhombencephalon. Craniofacial underdevelopment was characterized by persistent open eye, cochlea with fewer turns, delayed closure of the palate, more simple nasal cavity, etc. The tongue was shorter and convex upward, that were especially prominent at 14 days of gestation. The convex tongue and underdeveloped brain made the cranial base convex upward, and the angle between the cranial base an vertebral axis more obtuse. Small head with increase cephalic index and midfacial hypoplasia appeared to account for brain underdevelopment.

The Effect of Preoperative Treatment on Cell Kinetics and Patients Survival in Hepatocellular Carcinoma.: Yoon Jung Choi, Ho Guen Kim, Chan Il Park, Woo Hee Jung; Korean J Pathol. 1994;28(6):605-611.

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Abstract PDF: To evaluate the effect of preoperative treatment on proliferative activity and prognosis of the hepatocellular carcinomas(HCCs), fifty-three surgically resected HCCs were studied. Twenty cases were treated preoperatively and thirty-three were not treated before surgery. The proliferation index(PI, % of proliferating cell nuclear antigen positive cells) of the remaining cancer cases(35.41). Although PI was similar among gross types and among histologic grades, tumors of the expanding type and of the histologic grade I revealed distinctly low PI in pretreated cases. Two-year survival rate was not significantly different between pretreated and not-pretreated cases(67.4 vs 52.7). But the differences between gross types(p<0.05) and between histologic grades(p<0.01) were significant. Total necrosis of tumor occurred in five pretreated patients, all of whom were alive during two-year follow-up. Smaller HCCs showed better prognosis(p<0.01). Although PI appeared not correlated well with the two tear survival rate, the pretreated HCCs preoperative modalities induce tumor necrosis, but do not reduce the proliferative activity of tumor cells significantly, and that pretreatment does not affect the long-term prognosis of HCCs except for the accasions of total necrosis of tumor.

Relationship between Immunohistochemical Expression of Cathepsin D and Other Prognostic Factors of Breast Carcinoma.: Kwang Hwa Park, Byeng Woo Park, Kyong Sik Lee, Kwang Gil Lee; Korean J Pathol. 1994;28(6):612-619.

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Abstract PDF: The cathepsin D is a lysosomal protease secreted in excess by breast cancer cells. The function of this enzyme is degradation of the extracellular matrix and proteoglycan. It is induced by estrogens in estrogen receptor positive breast cancer cell lines. On the basis of this, cathepsin D expression in breast cancer cells seems to be correlated with the prognosis. But there is debates in its prognostic significance. Relationship between cathepsin D expression and other prognostic factors of breast cancer was studied. We investigated 51 cases of invasive ductal cell carcinoma of breast removed by open biopsy or mastectomy. All cases were fixed in formalin and embedded in paraffin. We used 46-KD intermediate form of the enzyme for cathepsin D expression on immunohistochemical stain. We observed no significant correlation with age, stage, histologic grade, lymphatic invasion, and estrogen receptor status. Cathepsin D may be an independent factor which is not related with other prognostic factors, especially estrogen receptor status.

Hepatoid Adenocarcinoma of the Stomach: A Pathologic Analysis of 14 cases.: Gyeong Hoon Kang, Yong Il Kim; Korean J Pathol. 1994;28(6):620-628.

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Abstract PDF: Hepatoid adenocarcinoma of the stomach has been designated to a primary gastric adenocarcinoma with minimum criteria of elevated serum alpha-fetoprotein and its histological resemblance to neoplastic liver cells. Of the 1,500 consecutive cases of surgically resected gastric carcinomas during a period of 4 years, we retrieved 14 cases of adenocarcinoma which met the histologic features of hepatoid growth and compared them histologically with 400 consecutive cases of non-hepatoid gastric adenocarcinomas. The patient's age ragned from 32 to 80 years(non-hepatoid group: 25 to 81 years) and their male to female ratio was 3.7 : 1(non-hepatoid group: 1.8 : 1). Grossly, five case were Borrmann type II and another five cases type III. All three cases of early gastric carcinomas were the submucosal type IIc. The remaining one was an advanced gastric carcinoma mimicking early gastric carcinoma. Microscopically, the hepatoid portions varied in growing patterns and arranged in either compact, trabecular or pseudoglandular pattern and gave an immunoreactivity to alpha-fetoprotein and alpha-1-antichymotrypsin. Regardless of the tumor stage, the hepatoid areas were located in the deeper portion of the tumor mass and grew in an expanding/nodular pattern. The associated adenocarcinomatous areas were mostly papillotubular, moderately to well differentiated, and frequently revealed clear PAS-negative cytoplasm reminiscent of the differentiated embryonal carcinoma. Tumor emboli and nodal metastasis were the frequent associations. We assume that the hepatoid adenocarcinoma may develop from gastric'adenocarcinoma through embryonal carcinomatous growth.

Immunohistochemical Study on Pituitary Aednoma.: Yong Hee Lee, Tai Seung Kim; Korean J Pathol. 1994;28(6):629-635.

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Abstract PDF: The development of immuohistochemistry and the application of electron microscopy have revolutionized our understanding of the pathopysiology of pituitart adenoma. The clinical value of functional characterization of pituitary adenoma has been realized. Immunohistochemical stains using polyclonal antibodies to six pituitary hormones (GH, PRL, ACTH, TSH, FSH & LH) were performed to classify the pituitary adenoma and to investigate the relationship between the results of the immunohistochemical study and pared to the serum hormone level. The results are summarized as follows: The Most common clinical type of pituitary adenoma was prolactinoma and the second was nonfunctioning adenoma. However, the most common immunohistological type of pituitary adenoma was null cell adenoma, the second one, lactotrope adenoma and the third one, mixed sommatotrope & lactotrope adenoma. In the clinically nonfunctioning adenoma cases, null cell adenoma were present in 75%; gonadotrope adenoma and corticotrope adenoma were present in 25%, while the serum prolactin level was increased in ten of the twenty cases(50%) of the null cell adenoma. When the serum prolactin level was increased above the 150ng/ml, the tumor cells gave positive reactions in 95.2% of cases immunohistochemically. But in the cases of GH, FSH & LH, the tumor cells gave positive reactions in 100%, 75%, and 66.7%, respectively. In the case of increased serum prolactin level, more than 50% and 30% proportion of tumor cells showed positive reactions in the micro- and macroadenoma, respectively.

Immunohistochemical Profile of Sclerosing Hepatic Carcinoma.: Chan Il Park, Young Nyun Park; Korean J Pathol. 1994;28(6):636-642.

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Abstract PDF: Sclerosing hepatic carcinoma (SHC) is composed of slender cords or small nests of tumor cells with peripheral palisading, and abundant intervening sclerosis. The tumor seems to have the histologic features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma. To evaluate the phenotypic expression of SHC and to investigate its cellular origin, immunohistochemical studies on three cases of SHC were performed. In all cases, the tumor cells showed positive staining for cytokeratins AE1, AE3 and 19, carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). The expressions of cytokeratins AE1 and 19 were stronger in the palisading cells than the interior of the cords and nests. Conversely, CEA and EMA were expressed mainly in the inner portion. Alpha-fetoprotein was expressed in only one case, mainly in the palisading cells. In summary, SHC has the histological as well as the immunohistochemical profiles intermediate between HCC and cholangiocarcinoma, and the immunohistochemical profile suggests that SHC arises from primitive hepatoblast with a tendency of differentiation to the bile duct epithelium.

The Study of Histopathologic Grade, PCNA and AgNORs Staining in the Recurrent Urinary Bladder Cancer.: Soo Yeon Cho, Woon Sub Han; Korean J Pathol. 1994;28(6):643-650.

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Abstract PDF: The prognosis of transitional cell carcinoma(TCC) of the urinary bladder is related to histopathologic parameters, among which the clinical stage and histopathologic grade are most important prognostic determiantors. Recently the immunohistochemical assessment of proliferating cell nuclear antigen(PCNA) and nucleolar organizer region number(AgNORs) can obtain the PCNA, and AgNORs stainings were studied in 55 the sequential biopsies of 22 recurrent TCCs of the urinary bladder. 6 cases showed the increased changes of grade, of which 5 cases was independently to the change of grade. The AgNORs in 18 cases showed increase in 10 cases. The comparison between PCNA count and AgNORs score according to grade was performed in the changes between grade II and III, both PCNA count and AgNORs score were increased with in crease of grade. However, The change of the PCNA count was stastically significant, but not AgNORs score.

Amniotic Fluid Embolism of Lung: Clinical and histopathological study.: Tae Jung Kwon; Korean J Pathol. 1994;28(6):651-656.

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Abstract PDF: Amniotic fluid embolism is caused by the infusion of amniotic fluid into the maternal circulation with embolization to the lungs during pregnancy, labor or just after delivery. Clinically, this condition combines acute cardiopulmonary failure with a hemorrhagic tendency. We have experienced 11 autopsy cases of amniotic fluid embolism for about 2 years. The most common presenting feature was the postpartum uterine bleeding, followed by shock during oxytocin-induced labor. Histologically, various amount of amniotic debris, among which the most common component was epithelial squames, was demonstrated within the pulmonary vasculatures. In 4 cases, many fibrin thrombi were noted, reflecting the coagulation defect. Masson's trichrome and Alcian blue stains were proven to be valuable to demonstrate the squames and mucin, respectively.

Combined Pneumocystis Carinii Pneumonia and Miliary Tuberculosis in a Patient with AIDS.: So Young Park, Hye Kyung Lee; Korean J Pathol. 1994;28(6):657-662.

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Abstract PDF: Patients with AIDS frequently present with pulmonary complications which are associated with a high mortality rate and infections are the most important cause of lung infiltrates. In addition to pneumonia caused by Pneumocystis carinii, which was noted in early reports of the syndrome, a variety of other severe pulmonary disorders may occur. Frequently more than one organism is found in a single patient and among these, combined infections of Pneumocystis carinii and cytomegalovirus are the most common. We experienced a case of combined Pneumosytis carinii and Mycobacterium tuberculosis infection as a pulmonary manifestation of AIDS in a 38-year-old man. In bronchoalveolar larvage, bronchial washing and brushing, and sputum smear specimens, Pneumocystis carinii organisms were recognized, especially in Gomori's methenamine silver stains. Transbronchial lung biopsy specimen revealed intra-alveolar frothy exudates composed of collections of Pneumocystis carinii organisms as well as several granulomas with central caseous necroses.

Case Reports

Papillary Cystadenoma of the Epididymis: Component of von Hippel-Lindau Syndrome: A case report.: Yi Keong Chun, Won Ae Lee, Shin Kwang Khang; Korean J Pathol. 1994;28(6):663-665.

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Abstract PDF: Papillary cystadenoma of the epididymis is a rare benign tumor that represents the epididymal component of von Hippel-Lindau Syndrome. A case of epididymal papillary cystadenoma is presented in a 36 years old man. He also had pancreatic cysts, the pancreatic component of von Hippel-Lindau syndrome. His younger brother, who died of intracranial hemorrhage at age 27, revealed hemangioblastoma of the cerebellum, angioma of the retina and renal cell carcinoma on radiologic studies. These findings suggest familial occurrence of von Hippel-Lindau syndrome.

Hepatoid Adenocarcinoma of Stomach: A case report.: Jung Weon Shim, Hye Kyung Ahn, Young Cheol Lee, Joo Seop Kim, Young Euy Park; Korean J Pathol. 1994;28(6):666-668.

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Abstract PDF: A case of primary gastric carcinoma with patterns resembling those of hepatocellular carcinoma(HCC) is reproted. This patient who represented high serum alpha-fetoprotein(AFP) underwent a subtotal gastrectomy for stomach cancer and lobectomy of liver metastasis. The hepatoid component of the tumor was characterized by solid nests of large polygonal cells arranged in cords and trabeculae, with central nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm; single-nuclear giant cells were frequently noted. These tumor cells of stomach stained positive immunohistochemically for AFP, ACT(alpha-1-antitrypsin), AACT(alpha-1-antichy-motrypsin). Thus, this hepatoid gastric adenocarcinoma tumor cells demonstrated both morphologic and immunohistochemical features of partial differentiation to the HCC. Careful histologic examination in conjunction with the immunohistochemical demonstration of AFP can provide a useful contribution to the diagnosis of this rare histological type of gastric carcinoma And the presence of metastatic hepatoid adenocarcinoma from the stomach should be considered in a patient with hepatic tumor mimicking HCC. Because of frequent venous and lymphatic invasion, as well as liver metastasis, prognosis appears to be poor. The authors reviewed 45 cases of hepatoid adenocarcinoma of stomach reported in the literature, also.

Glomus Tumor of Stomach: A case report.: Young Ha Oh, Chan Pil Park, Chan Kum Park, Sung Jun Kwon, Jung Dal Lee; Korean J Pathol. 1994;28(6):669-672.

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Abstract PDF: Gastric glomus tumor is an uncommon benign, submucosal neoplasm and does not require radical surgical procedure. Because there are no specific clinical or radiologic features associated with the glomus tumor, it can be recognized only by its histologic characteristics. We report a 30-year-old woman who had 10 years history of epigastric hunger pain. Radiologically, a gastric submucosal tumor was discovered, which was suggestive of leiomyoma. Gastric antrectomy was performed. The tumor cells showed immunohistochemical and ultrastructural evidence of smooth muscle differentiation.

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