Journal of Pathology and Translational Medicine

Volume 30(2); February 1996

Original Articles

Ultrastructural Changes in Rat Kidney after Lead Acetate Administration.: Hyun Chul Kim, Seung Pil Kim, Kwan Kyu Park; Korean J Pathol. 1996;30(2):73-88.

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Abstract PDF: This study was carried out to investigate the ultrastructural findings of rats after administration of 0.5% lead acetate with drinking water. The Sprague-Dawley rats were divided into control and experimental groups. The control group was composed of 12 rats and was orally administered with 0.5% sodium acetate. The experimental group was composed of 36 rats and orally administered with 0.5% lead acetate. Two rats in the control group and four rats in the experimental group were sacrificed on day 2, and week 1, 2, 4, 6 and 8 after administration. The kidney was extirpated and examined by electron microscopy. The results obtained were as follows: The blood lead concentration in the experimental group began to increase from the second day after administration and it increased gradually until the 6th week and it decreased at the 8 week. The urinary excretion of delta-ALA also increased from the secondary and gradually increased up to the 8th week. On electron microscopic examination, the proximal tubular cells showed fat droplets, dilatation of the endoplasmic reticulum, mitochondrial swelling, increased numbers of secondary lysosomes and myelin figure-like residual bodies and intranuclear inclusion bodies. All these findings peaked at the eighth week after administration. Ultrastructural findings after Timm sulphide silver reaction revealed the lead granules in the proximal tubular lumen and between the microvilli of the proximal tubular cells without membrane-bounded. It can be concluded that most of the changes of micro-organelles are compatible with degenerative changes of lead exposure and passive diffusion of lead granules are involved in the proximal tubular cells.

Clinical Value of Demonstration of Estrogen and Progesterone Receptors using Paraffin Wax Sections in Breast Carcinoma.: Hye Kyung Ahn, Yun Jung Kim, Young Euy Park; Korean J Pathol. 1996;30(2):89-93.

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Abstract PDF: This study aimed at assessing the usefulness of paraffin wax sections for demonstration of ER(estrogen receptor) and PR(progesterone receptor), using brief microwave processing rather than proteolytic predigestion. The receptor status of a breast cancer is often into consideration when planning treatment nowadays. As biochemical receptor assays require large amount of fresh tumor tissue and are not always available for all tumors, pathologists are now increasingly asked to provide a service for the assessment of the receptor status in tissue routine sections. Until recently, immunohistochemical demonstration of receptors was used in frozen sections. Therefore, routinely processed paraffin wax sections of 25 cases of breast carcinoma with known ER and PR concentrations, estimated by the standard DCC(dextran-coated charcoal) biochemical assay, were examined using the ABC immunoperoxidase technique. The results were assessed semiquantitably, using a five grade scoring system. Of the 25 cases examined, with DCC cutoff point being <10 fmol,71% and 75% in positivity of each ER, PR receptor is concordant. Statistic analysis demonstrates high relationship between scoring system of IH method and DCC value in ER (R=0.6061, p=0.001) and PR (R=0.5832, p=0.001). The IH method can provide easily assessed reliable positive information about ER, PR status of breast carcinoma using routinely processed paraffin wax sections.

The Effect of Tamoxifen and Pentosan Polysulfate on the Microvessel Density and Cell Proliferation of Dimethylbenzanthracene-Induced Rat Mammary Carcinoma.: Chan Heun Park, Zhe Piao, Kwang Gil Lee; Korean J Pathol. 1996;30(2):94-105.

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Abstract PDF: Antiestrogen tamoxifen (TMX) is thought to elicit its therapeutic effect by competing with endogenous estrogens for the estrogen receptor. Several more recent studies asserted that the antitumor effect of TMX is not due solely to the inhibition of estrogen receptor-mediated action, but due partly to its capacity to inhibit angiogenesis and impair neovascularization. Despite extensive research and clinical experience with this drug, its exact mode of action in inducing tumor regression is still not clear. The present study is aimed toward the investigation of the effects of TMX on dimethylbenzanthracene- induced rat mammary carcinomas with respect to the tumor response to the drugs, histological changes, cell proliferative acitivity and angiogenesis inhibition, and if TMX has antiangiogenic action, to compare it with that of pentosan polysulfate (PPS), an already known antiangiogenic substance. Female Sprague-Dawley rats, aged 50 days, were divided into normal control, test control (tumor induction by dimethylbenzanthracene), TMX (TMX administration after tumor induction), and PPS (PPS administration after tumor induction) groups. Tumor response to the drug administration was classified according to changes of tumor volume as follows; complete response (CR), partial response (PR), no response (NR), and progressive disease (PD). The response rate of rat mammary carcinomas to the drug administration was significantly higher (p<0.05) in the TMX and PPS groups as compared with the test control group. There was, however, no statistical significance between the TMX and PPS groups. Necrosis was considerably frequent in tumors of the TMX and PPS groups. Hyaline change of the stroma was strikingly more common and marked in the TMX group and it was associated with atrophy of epithelial cells of the tumor glands. Proliferating cell nuclear antigen (PCNA)- labeling index of the tumors was significantly higher (p<0.05) in the tumors with NR and PD of the TMX group when compared with those with PR of the same group, which suggested a higher cell proliferative activity in these response groups. In the PPS group, however, there was no significant difference in PCNA index according to response. Microvessel density of the tumors was significantly lower (p<0.05) in the PPS group as compared with the test control and TMX groups and it was not related with response. The TMX group, however, did not show any significant difference in microvessel density when compared with the test control group. Microvessel density was significantly higher (p<0.05) in tumors with PD than those with PR in all 3 groups, which suggested a positive relation of increase in tumor size and angiogenesis. Based on these results it is thought that TMX and PPS inhibit growth of chemically-induced rat mammary carcinomas. It seems that the antitumor action of PPS is related with its antiangiogenic capability, but that of TMX does not have a relationship with angiogenenesis inhibition.

Immunohistochemical and Ultrastructural Study of Fibroblast Differentiation.: Chae Hong Suh; Korean J Pathol. 1996;30(2):106-114.

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Abstract PDF: The histogenesis of the myofibroblast continues to be a controversial issue. The most popular view is that the myofibroblast is derived directly from the fibroblast. The important role of myofibroblasts in the synthesis of collagen and in wound contraction was demonstrated initially in granulation tissue in experimental animals. Four settings are recognized in which myofibroblasts are the principal proliferative cells: reparative responses, pseudoneoplastic disorders, stromal response to neoplasia, and true neoplasms, both benign and malignant. To identify of fibroblastic cells with smooth muscle differentiation features in the nonneoplastic and neoplastic lesions, we examined a variety of histological, immunohistochemical and ultrastructural features of 7 cases of granulation tissue, 7 of hypertrophic scar, 10 of chronic persistent hepatitis, 10 of chronic active hepatitis, 7 of liver cirrhosis, 7 of fibromatosis, 42 of cervical intraepithelial neoplasia, 14 of microinvasive carcinoma, 14 of invasive carcinoma, 7 of fibroma, 20 of fibrosarcoma and 72 of malignant fibrous histiocytoma. Antibodies against alpha-smooth muscle actin and desmin were used in a biotin-streptavidin procedures. The results of immunohistochemical and electron microscopical examinations yielded virtually identical findings. The identification of fibroblastic cells with smooth muscle cell differentiation features in the desmoplastic reactions of carcinomas, fibroma, fibrosarcoma and malignant fibrous histiocytoma offers also novel diagnostic and prognostic perspectives, that might help in evaluating preneoplastic lesions and malignant lesions. So degree of proliferative myofibroblasts was helpful diagnostic aid in differentiation of chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis.

Gastric Carcinoma with Lymphoid Stroma: Pathologic and immunohistochemical study of 14 cases.: Eun Hee Lee, Woo Young Jang, Kyoung Chan Choi, Young Ran Shim, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1996;30(2):115-120.

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Abstract PDF: A total of 672 surgically resected gastric carcinomas were reviewed, and fourteen cases(2.1%) of "gastric carcinoma with lymphoid stroma" were identified. The tumor was located mostly in cardia and body portion(86%). Thirteen patients one was lost to follow up were alive without recurrence of tumor. Grossly, this carcinoma was characterized by an expanding growth pattern or a multinodular pattern. Histologically, this carcinoma showed an irregular trabecular and alveolar arrangement and densely infiltrated lymphoid cells with lymph follicles. The tumor cell nests were widely separated by non-desmoplastic lymphoid stroma. On immunohistochemical study, T cells were evenly distributed throughout the tumor lesion with intimate contact with individual carcinoma cells, but B cells were mainly present within the germinal centers of lymph follicles. Thus, the organized immune response combined with cell mediated and humoral immunities against the carcinoma cells may be a defense mechanism of the host in this type of gastric carcinoma.

The Studies of bcl-2 Oncoprotein and Epstein-Barr Virus Expression in Malignant Lymphomas: Immunohistochemical and in situ hybridization analysis on 66 cases.: Hye Jae Cho, Yeon Mee Kim, Hyun Ju Yoo, Jong Eun Joo; Korean J Pathol. 1996;30(2):121-131.

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Abstract PDF: Bcl-2 oncoprotein is being localized to mitochondria and interfering with programmed cell death (apoptosis) independent of promoting cell division in the lymphoid and nonlymphoid cells. The bcl-2 oncoprotein expression has been reported in follicular lymphomas as well as in diffuse non-Hodgkin's lymphoma, leukemia and a variable propotion of Hodgkin's lymphoma cases. Recent evidence suggests that some lymphomas protected from apoptosis is conferred through expression of Epstein-Barr virus(EBV) latent membrane protein which turn to cause upregulation of bcl-2. To define the role of the bcl-2 oncoprotein and EBV in lymphoid malignancy, we tried immunohistochemical studies with anti-bcl-2 antibody and In situ hybridization (ISH) with EBV-encoded small nuclear RNAs(EBER) in the paraffin embedded sections of 46 non-Hodgkin's lymphoma (NHL) cases and 20 Hodgkin's lymphoma (HL) cases. Bcl-2 oncoprotein expression was found in 37 of 46 cases (80%) of NHL with relatively strong cytoplasmic staining, and in 14 of 20 cases (70%) of HL with weak cytoplasmic staining in limited small numbers of RS, Hodgkin and lacunar cells. The widespread presence of bcl-2 oncogene in many different types of both NHL and HL supports that the extended cell survival through overexpression of bcl-2 gene protein may be a growth advantage of neoplastic lymphoid cells. In the ISH analysis for EBV, the presence of EBV was detected in 17 of 20 cases (85%) of HL, compared to 6 of 44 cases(13.6%) of NHL. It appears to be no direct correlation between overexpression of bcl-2 oncoprotein by neoplastic lymphoid cells and the presence of EBV in NHL but it seems to be a definite association between EBV and HL.

Correlation between Nuclear Grades and the Numbers of AgNORs and PCNA Labeling Indices in Renal Cell Carcinoma.: Hye Jin Lee, Young Im Han, Kang Suek Suh, Sun Kyung Lee; Korean J Pathol. 1996;30(2):132-139.

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Abstract PDF: The author examined the number of AgNORs and PCNA labeling indices by histochemical and immunohistochemical studies in 20 cases of renal cell carcinoma, composed of 5 cases according to the nuclear grades. The results obtained are summarized as follows; 1) Mean number of AgNORs according to the nuclear grades of renal cell carcinoma were 1.38+/-0.40 (mean+/-standard deviation) for Grade I, 2.53+/-0.33 for Grade II, 5.43+/-0.66 for Grade III, and 7.88+/-0.72 for Grade IV. The mean numbers of AgNORs according to the nuclear grades were significantly increased(p=0.0005). 2) PCNA labeling indices (positive nuclear ratio) according to the nuclear grades of renal cell carcinoma were 5.90+/-2.36 for Grade I, 19.30+/-6.71 for Grade II, 45.73+/-8.62 for Grade III, and 61.83+/-6.34 for Grade IV. Also, the PCNA labeling indices according to the nuclear grades were significantly increased(p=0.0008). 3) The mean numbers of AgNORs directly correlated with the PCNA labeling indices (r=0.9861, p<0.001). On the basis of the above results, it was considered that the numbers of AgNORs and PCNA labeling indices as markers of proliferative activity of tumor cells correlate well with the nuclear grades of renal cell carcinoma.

Immunohistochemical Analysis of Estrogen Receptors and Progesterone Receptors in Leiomyoma of Uterus Compared with PCNA Index.: Jung Ran Kim; Korean J Pathol. 1996;30(2):140-149.

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Abstract PDF: Estrogen receptor(ER) and progesterone receptor(PR) were studied immunohistochemically using specific antireceptor monoclonal antibodies in leiomyomas and myometrium from same patients from 38 women in various stages of the menstrual cycle, menopause and pregnancy. Two postpartum uteri are also included. Immunohistochemical localization was quantified as to intensity of staining and tissue distribution, and the results were compared with those of PCNA index. In all samples, ER and PR localized within the nuclei of target cells. The histochemical score of ER in leiomyoma was significantly greater than that found in myometrium. But ER in leiomyoma was expressed in cyclic fashion(r=0.45, P=0.006), like as in myometrium, throughout the menstrual cycle, paralleled by a concomitant, though delayed. In contrast, PR content constantly maintained in myometrium and leiomyoma throughout menstrual cycle, and there was no significant difference between them. However, leiomyoma and myometrium of pregnancy showed a significant reduction in the amount of ER and PR localized. PCNA index in leiomyoma(14.9+/-24.4) was also significantly higher than that found in myometrium(2.1+/-3.3). The index declined throughout the secretory phase. The leiomyoma had increased PCNA index during pregnancy, while the increasing rate in leiomyoma was lower than that of myometrium. The growth potential of leiomyomas is appearently higher than that of myometrium under the high progesterone level. The most of neoplasm with high PCNA index(10 above) contained absolute or relative abundant PR or ER content. Alteration of receptor content may be an important mechanism in steroid dependent growth of leiomyoma and may provide information useful in the clinical management of this neoplastic disorder.

Case Reports

Papillary Neoplasm of the Endolymphatic Sac: A report of two cases.: Jai Hyang Go, Yoon Jung Choi, Tae Seung Kim, Chan Il Park; Korean J Pathol. 1996;30(2):150-154.

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Abstract PDF: Papillary tumor of the temporal bone or middle ear has been recognized as an aggressive neoplasm because of its invasive growth pattern. The site of origin is controversial so that most cases have been reported under various diagnostic terms. Recently, Heffner(1989) suggested that the endolymphatic sac is a possible site of origin, because the tumor resembles the endolymphatic sac in several aspects. We report two such cases. One patient was a 34-year-old female presenting with tinnitus and hearing difficulty for 1 year. Temporal bone CT revealed extensive bone destruction by the tumor which was located in the posterolateral aspect of temporal bone. The other patient was a 56-year-old female who complained of tinnitus, dizziness and otalgia for 2 years. Cranial MR imaging showed an irregularly marginated mass in the left jugular fossa with extension to the petrous bone. Histologically, both cases showed a papillary pattern and locally destructive growth that are typical of papillary tumor of the endolymphatic sac. The papillae were lined by a single layer of bland-looking cuboidal to low columnar cells. Immunohistochemically the lining cells expressed cytokeratin, epithelial membrane antigen, neuron specific antigen and in one case, S-100 protein, supporting the thesis that these neoplasms might be of endolymphatic sac origin.

Subcutaneous Fat Necrosis Associated with Pancreatic Adenocarcinoma: A case report.: Hee Jung Kim, Kwang Gil Lee; Korean J Pathol. 1996;30(2):155-160.

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Abstract PDF: Subcutaneous fat necrosis is manifested by erythematous tender nodules on the legs, buttock or trunk and is associated with pancreatic disease including acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, pancreatic stone and other diseases. Its histologic findings are pathognomonic and reveal foci of subcutaneous fat necrosis with "ghost-like" anucleated cells with thick "shadowy wall" and surrounding inflammatory infiltrate consisting of polymorphonuclear cells, eosinophils, lymphocytes, histiocytes, foam cells and foreign body giant cells. We experienced a case of subcutaneous fat necrosis associated with pancreatic adenocarcinoma manifested by subcutaneous nodules in the buttock and lower extremities and by arthralgia of the left knee in a 67-year-old woman. Therefore, we are reporting to emphasize the importance of the skin findings of the internal disease.

Large-Cell Acanthoma: A case report.: Yu Hoon Kim, Seong Jin Cho, Ae ree Kim, Nam Hee Won, Kye Yong Song; Korean J Pathol. 1996;30(2):161-163.

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Abstract PDF: Large-cell acanthoma is a generally hyperkeratotic, sharply demarcated patch on sun-exposed skin with the outstanding pathologic feature being composed of large, relatively uniform keratinocytes. We describe a case of large-cell acanthoma that involved the skin of the nasal bridge. Patient was a 56-year-old women with a tannish brown patch, 2 cm in size and of 5 years' duration. Controversial issues about nosologic entity of large cell acanthoma are discussed.

Galactocele in a Male Child: A case report.: Yoon Mi Jeen, Yoon Jeong Choi, Dong Wha Lee, Chan Il Park; Korean J Pathol. 1996;30(2):164-165.

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Abstract PDF: We investigated a unilocular mammary cyst occurring in a two and a half year old male baby. The cyst was lined by simple columnar epithelium and filled with a milky secretory material. These histologic features were consistent with galactocele. The child had enlarged left breast since birth, but it seemed to be noncontributory as the child had neither endocrine abnormalities nor perinatal disorders. Galactocele is an uncommon breast lesion usually occuring in females following lactation. It is rarely a cause of breast enlargement.

Unilateral Pulmonary Agenesis Combined with other Unusual Anomalies: An autopsy report.: Ik Su Kim, Sang Han Lee, In Soo Shu; Korean J Pathol. 1996;30(2):166-168.

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Abstract PDF: Pulmonary agenesis is a very rare anomaly. It is defined as total absence of the pulmonary parenchyma, vascular structures, and bronchi beyond the carina. We experienced a case of right pulmonary agenesis in association with other congenital defects who died at 1 day of age. The other defects included: esophageal atresia, tracheoesophageal fistula, cardiac malformation, anal atresia and a malformed left thumb. The cardiac malformations were a type of Pentalogy of Fallot, composed of right ventricular hypertrophy, ventricular septal defect, an overiding of aorta, pulmonary atresia, and an atrial septal defect. Hand roentgenograms of the malformed left thumb showed an unarticulated metacarpopharyngeal joint. This unique combination of anomalies is extremely rare.

Functioning Parathyroid Carcinoma: A case report.: Kyoung Chan Choi, Won Hee Choi; Korean J Pathol. 1996;30(2):169-172.

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Abstract PDF: Parathyroid carcinoma is a relatively rare endocrine tumor, accounting for approximately 1 to 5% of patients with primary hyperparathyroidism. Patients with parathyroid carcinomas are often symptomatic, have markedly elevated calcium levels, and have a palpable cervical mass. They are equally distributed between the sexes and usually present 10 years before their benign counterparts. The diagnosis is suspected when the tumor is large, parathyroid hormone levels are high, and a palpable mass is present in the neck. Parathyroid carcinoma is often misdiagnosed preoperatively, suspected intraoperatively, and only confirmed postoperatively. We experienced a case of hyperfunctioning parathyroid carcinoma in a 36 year old man, which was confirmed microscopically. The tumor showed: 1) capsular and blood vessel invasion; 2) frequent mitotic figures in the parenchymal cells; 3) a trabecular pattern, and 4) intervening thick fibrous bands. Immunohistochemical stain of p53 may be one of the useful methods in identifying malignancy of parathyroid gland.

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