Journal of Pathology and Translational Medicine

Volume 33(5); May 1999

Original Articles

Expression of CDK 4, Connexin 32, and PCNA in N-diethylnitrosamine-Induced Lesions of Rat Liver.: Bang Hur, Hung Jun Kim; Korean J Pathol. 1999;33(5):309-318.

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Abstract PDF: Cellular altered foci (CAF), hyperplastic nodules (HN) including regenerating and adenomatous nodules, and hepatocellular carcinomas (HCC) were induced in Sprague-Dawley rat liver by prolonged administration of N-diethylnitrosamine (DEN, 200 ppm). Immunohistochemical expression of connexin 32 (Cx 32), cyclin-dependent kinase 4 (CDK 4), and proliferating cell nuclear antigen (PCNA) was assessed for the evaluation of preneoplastic potential of CAF. Regardless the duration of DEN administration, basophilic cell foci were the most frequently observed lesion in both CAF and cellular expanding hyperplastic nodules. Eosinophilic cell foci, however, were concomitantly increased with adenomatous nodules in later experimental groups. Cx 32 showed perimembranous spot-like expression. Its number was 7.25 2.10 per cell in normal hepatocytes. CAF and adenomatous nodules showed markedly decreased Cx 32 spots. Moreover, its reduction was more prominent in HCC. PCNA-labelled hepatocytes were scattered in the most CAF, showing no significant difference between each CAF. PCNA labelling index (LI) in adenomatous nodule and HCC was markedly increased. CDK 4 was localized in the cytoplasm and/or nucleus of hepatocytes. Eosinophilic cell foci revealed more nuclear expression of CDK 4 than other types of CAF, of which expression incidence was comparable to that of adenomatous nodule. Nuclear CDK 4 expression in HN and HCC was increased, although significant difference between regenerating nodule and adenomatous nodule was not seen. In conclusion, the incidence of CDK 4 was concomitantly increased with PCNA LI, however, reciprocally decreased with Cx 32 in accordance with the advance of DEN-induced HCC in rat. Phenotypically altered foci manifested as CAF are early valuable preneoplastic marker lesion for evaluation. In addition, basophilic cell foci can be considered a discernible marker of cellular expansion within nodules. However, eosinophilic cell foci might be an indeterminate marker for the advance of DEN-induced HCC in rat.

Inhibitory Effect of Tetrandrine on Extracellular Matrix Deposition in Rat Hepatic Fibrosis.: Won Young Choi, Hyo Jeong Chae, Sun Kyung Lee; Korean J Pathol. 1999;33(5):319-325.

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Abstract PDF: No effective therapy has yet developed for liver fibrosis/cirrhosis by directly inhibiting the accumulation of extracellular matrix. This study was undertaken to determine the effect of tetrandrine in rat model of liver fibrosis induced by carborn tetrachloride (CCl4) administration intraorally. Tetrandrine, a calcium channel blocker, is anti-inflammatory constituent of the families Menispermaceae and Ranunculaceae, which have been used as folk remedies in China. Repeated administration of CCl4 for 14 weeks to rats induced liver fibrosis with steatosis. Rats were killed after 4, 8 or 14 weeks of treatment with CCl4, CCl4 tetrandrine (30 mg/kg) or CCl4 tetrandrine (50 mg/kg). The histopathological findings of liver were observed semi-quantitatively by light microscopy and volume percentage of the collagen deposition was determined by image analyzer. Tetrandrine inhibited collagen deposition induced by CCl4 administration, as shown by less severe steatosis and fibrosis and significantly decreased volume percentage of collagen fibers in CCl4 tetrandrine treated animals compared with CCl4 only group. Thus, the administration of tetrandrine holds great promise for treating subjects with liver fibrosis/cirrhosis as a result of chronic hepatic injury.

Relationship between Insulin Secretory Capacity and Mitochondrial Morphology in Pancreatic beta-Cell.: Seung Won Yang, Jae Hyuk Lee, Chang Soo Park, Min Young Chung; Korean J Pathol. 1999;33(5):326-336.

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Abstract PDF: To investigate the relationship between insulin response and morphometric changes of the mitochondria of pancreatic beta-cell, this study was performed using hyperglycemia and streptozotocin as oxidative stresses. Adult and neonatal rats were used. Intravenous glucose tolerance test (IVGTT) and morphologic examination of pancreas using immunohistochemical stain, in situ end-labeling method and electron microscopic study were performed. Various mitochondrial parameters were measured by image analyzer. Immunohistochemical stain revealed a markedly reduced islet size and decreased number of beta-cells and the increased number of non-beta-cell in adult and neonatoal streptozotocin group, and the appearance of insulin positive cells throughout the exocrine parenchyma in neonatal streptozotocin group. Three days after injection of streptozotocin in adult streptozotocin group, TUNEL stain showed increased apoptotic cells in islets. Ultrastructurally, beta-cells in adult streptozotocin group showed increase in number and size of mitochondria, and disruption of mitochondrial structures. Hyperglycemic group and neonatal streptozotocin group showed preserved mitochondrial ultrastructure. Ultrastructural morphometric study revealed increase in size and number of mitochondria and decrease in mitochondrial contour index in adult streptozotocin-treated rats, which suggested mitochondrial degeneration. Hyperglycemic group showed mild increase in size of mitochondria. Increased number of mitochondria was also observed in neonatal streptozotocin group. IVGTT revealed marked decrease in insulin response in adult streptozotocin group, and non-insulin-dependent diabetes mellitus pattern in glucose and insulin response in neonatal streptozotocin group. Hyperglycemic group showed a glucose and insulin response similar to control group. The above results suggest that a severe oxidative injury may cause degeneration and disruption of mitochondria of pancreatic beta-cell, and may be associated with substantial apoptotic cell death. The changes in the morphology and the number of mitochondria may result from streptozotocin treatment within neonatal period and hyperglycemia treatment, which may be associated with changes in insulin response.

Histological Grading and Staging of Chronic Hepatitis Standardized Guideline Proposed by the Korean Study Group for the Pathology of Digestive Diseases .: Young Nyun Park, Ho guen Kim, Chae Yoon Chon, Jae Bok Park, Jin Hee Sohn, Seung Ha Yang, Eun Sil Yu, Mi Seon Lee, Ja June Jang, Hee Kyung Chang, Jong Jae Jeong, Dae Young Kang, Yong Il Kim, Chan Il Park; Korean J Pathol. 1999;33(5):337-346.

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Abstract PDF: The terms chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and chronic lobular hepatitis (CLH) should be discontinued in favor of etiologic terminology. The activity of necro-inflammation and the degree of fibrosis should be evaluated for grading the severity and for the stage of disease. Members of the Korean Study Group for the Pathology of Digestive Diseases reviewed 30 cases of chronic hepatitis and reached the following consensus: 1) The pathology report of the biopsy samples with features of chronic hepatitis should include the etiology, grade and stage. 2) Grade and stage should be semiquantitatively evaluated as none, minimal, mild, moderate and severe. 3) For grading, lobular activity and periportal activity should be evaluated, separately. 4) To avoid confusion with other grading systems, simple report using descriptive terms rather than numerical records is recommended in daily practice. Criteria for each grade and stage should be presented and discussed. Histologic grading and staging of chronic hepatitis by new standardized guidelines will give more information about the prognosis as well as the present status of hepatitis. The terms CAH, CPH and CLH may be used in parentheses to facilitate relearning.

Expression of p53 Protein in Endometrial Carcinoma.: Mi Jin Kim, Dong Suk Kim; Korean J Pathol. 1999;33(5):347-352.

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Abstract PDF: The mutation of p53, a tumor suppressor gene, has been considered to play an important role in tumorigenesis in a variety of human cancers and the abnormal expression of p53 are frequently associated with poor prognosis. In order to examine the association of p53 overexpression with known prognostic factors including estrogen receptors (ER) and progesterone receptors (PR), we studied the status of p53 protein expression by immunohistochemical staining of paraffin sections of 29 endometrial carcinoma (25 endometrioid carcinoma, 2 clear cell carcinoma, and 2 serous carcinoma), obtained from hysterectomy. The results were as follows: The expression of p53, ER, and PR was present in 9/29 (31%), 3/29 (16%), and 12/29 (48%), respectively. The expression of p53 in endometrioid adenocarcinoma was present in 6/25 (24%) and showed significant correlation with histologic grade, nuclear grade, and myometrial invasion. The status of PR showed significant inverse correlation with histologic grade, nuclear grade and myometrial invasion. There was no significant correlation between ER status and these histologic factors. The expression of p53 was inversely associated with the status of PR, but statistically not significant. Our results indicate that p53 may be useful in predicting prognosis in endometrial carcinoma and will be able to provide helpful information in predetermination of aggressive behavior of the tumor in evaluation of curettage specimen.

Morphohistometric Investigation and bcl-2 Expression in the Placenta of Chromosomally Abnormal Pregnancy.: Joung ho Han, Kyu Rae Kim, Yeon Lim Suh, Mi Kyung Kim, Young Hyeh Ko, Dae Shick Kim, Howe Jung Ree; Korean J Pathol. 1999;33(5):353-360.

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Abstract PDF: To evaluate the significance of placental histology, a collaborative histological and cytogenetic study was performed on the products of 88 spontaneous abortions, and subsequently bcl-2 immunostaining was performed on 62 cases. The morphometric parameters included were DCIRCLE, FORMSHAPE, CPRATIO, and the expression of bcl-2 immunostainig was graded in four categories (I to IV). The results were as follows: 1) 40% (n=35) were chromosomally abnormal: trisomies predominated (57%, n=20) and was followed by triploidy (14%, n=5), double trisomy (6%, n=2), monosomy X (6%, n=2), inversion (9) (6%, n=2). 2) mean of DCIRCLE in chromosomally abnormal pregnancy was 40 micrometer larger than that in chromosomally normal pregnancy (p=0.012, one side t-test), while no difference was found in FORMSHAPE and CPRATIO between chromosomally abnormal and normal pregnancy. 3) bcl-2 expression was found in syncytiotrophoblast and cytotrophoblast. bcl-2 expression was weaker in chromosomally abnormal pregnancy with intensity I and II of 59% than chromosomally normal pregnancy with intensity I and II of 24%. 4) In comparison bcl-2 expression with DCIRCLE, in chromosomally normal abortion one (10%) in I & II and one (3%) in III & IV showed large DCIRCLE (above 360 micrometer), while 11 (85%) in I & II and 3 (33%) in III & IV in chromosomally abnormal pregnancy. It would mean that bcl-2 protein is necessary in preservation of pregnancy and placental morphology. Abnormal villous diameter and weak bcl-2 expression may be suggestive of chromosomal anomaly. Besides other histologic parameters, application of bcl-2 immunostaining and morphometric analysis probably give more sensitive and specific results in identifying chromosomally abnormal abortion.

Case Reports

Analysis of Pulmonary Asbestos Body in Malignant Mesothelioma: A case report.: Hoon Kyu Oh, Jae Yoe Ro, Chul Jong Yoon, Je Geun Chi; Korean J Pathol. 1999;33(5):361-366.

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Abstract PDF: The association between occupational asbestos exposure and the subsequent development of malignant mesothelioma of pleura is well recognized. We analyzed an asbestos body by energy dispersive X-ray analyser in a case of malignant mesothelioma of pleura who had a history of asbestos exposure 30 years ago. In transmission electron microscope, the asbestos body was composed of a core of refractile thin asbestos fiber bundle and beaded masses of electron-dense iron and protein complex. The core fibers were analyzed as an amphibole type crocidolite fiber [(Na2Fe3Fe2(Si8O22)(OH)2] which composed of high content of silicon, iron and sodium.

Emphysematous Pyelonephritis in Diabetic Nephropathy A report of two cases.: Jae Ho Han, Lucia Kim, Sung Eun Kim, Soon Won Hong, Hyeon Joo Jeong; Korean J Pathol. 1999;33(5):367-370.

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Abstract PDF: Diabetic nephropathy is characterized by one or a combination of the following lesions: (1) glomerular involvement with three distinctive patterns: diffuse glomerulosclerosis, nodular glomerulosclerosis, and exudative lesions; (2) arteriolo sclerosis; (3) urinary tract bacterial infection with pyelonephritis and sometimes emphysematous pyelonephritis. Emphysematous pyelonephritis is an uncommon life-threatening and acute suppurative infection of the kidney, and usually occurs in diabetic female patients. It is characterized by the production of intraparenchymal gas. Glucose fermentation has been considered the main cause of the gas formation. We presented two illustrative nephrectomy cases of emphysematous pyelonephritis in addition to the typical pathologic features of diabetic nephropathy.

Undescended Testis in the Complete Testicular Feminization Syndrome A report of three cases.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Jung Ho Lee, Jong In Kim; Korean J Pathol. 1999;33(5):371-375.

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Abstract PDF: The testicular feminization is the most common type of male pseudohermaphroditism. Mutation of androgen receptor gene impairs normal sexual differentiation in genetic male (46, XY) and subsequently develops secondary female characteristics. We report three cases of complete testicular feminization syndrome with normal development of female external genitalia, but with blindly ended vagina and inguinal or pelvic masses. Microscopic examination of the testes and their adnexa had three components: 1) A testis composed of immature tubules, prominent Leydig cells and a spindle cell stroma resembling ovarian stroma with hamartomatous nodule or Sertoli cell adenoma, 2) a white, whorled, firm, smooth muscle body in the medial pole of the testis, and 3) a lateral adnexal cysts of varying sizes.

Juvenile Granulosa Cell Tumor Arising in Undescended Testis: A case report.: So Ya Paik, Hae Youn Kang, Jae Ho Han, Woo Ick Yang, Seok Joo Han; Korean J Pathol. 1999;33(5):376-379.

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Abstract PDF: Juvenile granulosa cell tumor is rare but one of the common congenital testicular neoplasms. Although histological features are typical of its ovarian counterpart, testicular juvenile granulosa cell tumor has a distinctly different clinical presentation. We report a case of juvenile granulosa cell tumor arising in the cryptochid testis of a 4-day-old newborn. A 6 5 5 cm sized multilocular cyst containing thick, mucinous fluid was found in the peritoneal cavity. The external surface of the cyst was smooth and the septae were relatively thin. The cyst consisted of numerous mucin-filled, cystic follicles lined by cells having vacuolated cytoplasm and round to oval dark nuclei without grooves. Cells resembling granulosa cells of an ovarian follicle were also observed in the intervening stroma forming irregular solid nests.

Granulosa Cell Tumor Arising in the Paratesticular Area: A case report.: Soo Kee Min, Tae Jin Lee, Joo Ryung Huh, Tae Han Park, Jae Yoon Ro; Korean J Pathol. 1999;33(5):380-384.

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Abstract PDF: Granulosa cell tumor of the testis is extremly rare in adult males and granulosa cell tumor occurring in the paratesticular area has not been reported. We report a paratesticular granulosa cell tumor in a 34-year-old man who presented with a 5.5 cm sized scrotal mass. The tumor was present in the paratesticular area near the head of epididymis. It was located in the tunica and completely separated from the testis by thick fibrous tissue. Microscopically, the tumor exhibited solid, microfollicular, and trabecular patterns. The tumor cells had ovoid to elongated nuclei with longitudinal intranuclear grooves and one or two nucleoli and scanty cytoplasm. Mitoses were relatively frequent with an average number of 9/10 HPFs. The tumor extended into the visceral tunica vaginalis and showed multiple lymphatic tumor emboli. Immunohisto chemical stains revealed diffuse strong positivity for inhibin, vimentin, and keratin and diffuse weak positivity for estrogen and progesteron receptor. Placental alkaline phosphatase (PLAP) and epithelial membrane antigen (EMA) were negative. On electron microscopic examination, tumor cells were polygonal and had large indented nuclei. The cytoplasm contained a moderate number of small round mitochondria, abundant rough and smooth endoplasmic reticula, and a few lipid droplets. Small aggregates of intermediate filaments and intercellular junctions were observed. The patient was alive and well 5 months after orchiectomy. This is the first case of adult granulosa cell tumor arising in the paratesticular area.

Signet Ring Cell Carcinoma of the Prostate A report of two cases.: Yu Na Kang, Sang Sook Lee, Tae Jin Lee, Jae Yoon Ro; Korean J Pathol. 1999;33(5):385-368.

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Abstract PDF: Primary signet ring cell carcinoma of the prostate is extremely rare and about 18 cases have been reported in the literature. We report two cases of primary signet ring cell carcinoma of the prostate, arising in 79-year-old and 65-year-old men. Both cases were the poorly differentiated adenocarcinoma of the prostate with many signet ring cells. Signet ring cells were positive for prostatic specific antigen and prostatic acid phosphatase but negative for neutral and acid mucins. In summary, the signet ring cell carcinoma of the prostate is a rare variant of poorly differentiated adenocarcinoma of the prostate. The orgin of the prostate should be considered in cases of metastatic signet ring cell carcinoma, particularly when the signet ring cells are negative for neutral and acid mucins. Prostatic specific antigen and prostatic acid phosphatase should also be performed to confirm the primary signet ring cell carcinoma of the prostate.

Adenoid Cystic Carcinoma of the Male Breast: A case report.: Mi Kyung Lee, In Chul Hong, Woo Ick Yang, Sang Ho Cho; Korean J Pathol. 1999;33(5):389-392.

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Abstract PDF: A 65 year-old male patient presented with a large palpable mass beneath the areola of the right breast for 7 years. The resected breast tissue was almost totally replaced by a round large solid mass (9 6 cm) with a pink-gray to yellow firm, partly nodular cut surface. Microscopically, the tumor revealed the diagnostic biphasic cellular pattern of adenoid cystic carcinoma, which consisted of both cribriform pattern of myoepithelial cells and tubular pattern of epithelial cells. On immunohistochemistry, the tumor revealed immunoreactivities for alpha-smooth muscle actin and S-100 protein in the myoepithelial cells and for AE1/AE3 in the epithelial cells. Mitoses were scarce. Multifocal lymphatic permeation and foci of perineural invasion were also found. Underlying resection margins and overlying skin were invaded by the tumor. We diagnosed this tumor as grade II adenoid cystic carcinoma according to the system utilized for the salivary gland tumors.

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