Journal of Pathology and Translational Medicine

Volume 34(6); June 2000

Original Articles

Gene Expressions of Mouse Submandibular Gland during the Developmental Stage and Their Antisense Inhibition in Organ Culture.: Yeon Sook Kim, Suk Keun Lee, Je G Chi; Korean J Pathol. 2000;34(6):395-412.

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Abstract PDF: This study is aimed to observe the expressions of different genes, including the extracellular matrix proteins, growth factors, and transcription factors during different developmental stages of mouse submandibular gland. Reverse transcription-polymerase chain reaction (RT-PCR) and the antisense inhibition in organ culture system were performed using mouse embryos and newborns. Total 140 mouse embryos (E14(80), E15(20), E16(20), E18(20)) and 30 newborn mice (D2(10), D3(10), D6(10)) obtained from 60 pregnant mice and 3 adult mice (3 weeks old) were used for the cDNA production and the salivary gland organ culture. Syndecan, perlecan, laminin alpha1 chain, TGF beta1, beta 3, and sonic hedgehog mRNAs were expressed in the early stage (E14~E16) of the submandibular gland development, whereas transglutaminase C (TGase C), E-cadherin, epimorphin, laminin beta2 and gamma1 chains, and HGF mRNAs were expressed in the middle and late stages (E16~E18, D2~D6). Antisense inhibition of different genes in the organ culture of E14 mouse embryos of submandibular gland showed specific growth retardation in the development of ductal and acinar cells. Especially, the antisense inhibition of perlecan, E-cadherin, laminin alpha1 chain, laminin beta2 chain, and syndecan mRNA arrested the growth of ductal and acinar cells. While the antisense inhibition of integrin beta5 greatly affected the acinar cell differentiation and also produced cystic dilatation of salivary ducts, the antisense inhibition of fibronectin showed aberrant growth of ectomesenchymal tissues of the mouse submandibular gland.

Apoptosis in Rat Thymus after Bolus Intramuscular Injection of 5-Fluorouracil.: Kyung Hee Kim, Hae Joung Sul, Dae Young Kang; Korean J Pathol. 2000;34(6):413-418.

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Abstract PDF: We induced apoptosis in normal rats by intramuscular injection of 5-fluorouracil (5-FU) and immunohistochemically evaluated the thymus for the TdT-mediated dUTP biotin nick end labelling on the 1st, 3rd, 6th, 9th, 15th and 21st days following the bolus intramuscular injection. The injections of 5-FU induced a greater extent of apoptosis in the thymus. In the thymus, a mild increase in apoptosis was observed 24 hours after injection. The greatest number of apoptotic cells were seen at 72 hours. The size of the thymus decreased and the cortex thinned with hypocellularity. The injection of 5-FU caused massive cell loss in the thymus. Most apoptotic cells were scattered in the cortex and lower levels of apoptosis were also observed in the medulla. After 72 hours, the level of apoptosis returned to the control level. Considering the above results, we think that 5-FU induced toxicity may be related to 5-FU induced apoptosis in normal tissue, especially the thymus.

Histopathologic Change and Apoptotic Profile in Basal Ganglia of Rat Induced by Manganese Administration.: Chang Won Ha, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Dong Hoon Kim; Korean J Pathol. 2000;34(6):419-430.

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Abstract PDF: Mn (manganese) is known to induce Parkinsonian neurological disorder. Several lines of evidence suggest that apoptosis is involved not only in physiological cell death during normal development but also in neurodegenerative disease. The mechanism of Mn induced cell death remains poorly understood. In the present study, we evaluated the morphologic changes and apoptotic profile in basal ganglia using rat model of Mn toxicity. The rats were divided into three groups: the first group was a control; the second group was subdivided by administration dosage of Mn into group A (5, 10 mg MnC12/ kg) and group B (20, 40 mg MnC12/kg). The rats of each subgroup received a injection of Mn via tail vein every week for 4 weeks. The second group received 4 repeated injection of 10 mg MnC12/kg in the same manner and the rats were sacrificed at day 1, 3 & 7 in group I and at day 10, 21, 42, and 90 in group II after the last injection. A significant loss of neuron and gliosis were observed in the basal ganglia in the experimental groups (p<0.05), which were more pronounced in group II than in the control or group I. No significant difference in number of nerve cells or degree of gliosis was identified in the substantia nigra. Apoptotic cells were also increased in basal ganglia of experimental groups and appeared among neurons (10%), glial cells (10%), and endothelial cells (60%). Apoptotic figures were consistently noted through the entire experimental period after Mn injection in basal ganglia. In conclusion, these results demonstrate that Mn-induced cytopathic insult affects various cell types in basal ganglia and shows variable sensitivity in the different regions of brain, especially in the apoptotic cell death of the neuron. The overaccumulation of Mn in the brain might be attributed from the breakdown of blood-brain barrier due to the injury through the apoptosis.

Intrauterine Infection as a Cause of the Neonatal Pulmonary Injury and Bronchopulmonary Dysplasia.: Jin Haeng Chung, Jeong Wook Seo; Korean J Pathol. 2000;34(6):431-436.

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Abstract PDF: The pathogenetic role of intrauterine infection to the neonatal pulmonary injury and bronchopulmonary dysplasia was assessed by studying the interleukin-6 (IL-6) level in the umbilical cord blood and the early morphologic changes of the neonatal lung. Patients were grouped into bronchopulmonary dysplasia (4 cases), chorioamnionitis without chronic lung injury (4 cases), and 6 cases without morphologic evidence of chronic lung injury or placental inflammation. IL-6 level of umbilical cord blood was higher in babies with bronchopulmonary dysplasia (17.7 pg/ml) compared to those with chorioamnionitis (4.7 pg/ml) or those with morphologically normal lung and placenta (6.2 pg/ml). Morphologic parameters of neonatal pulmonary injury were hyaline membrane, terminal bronchiole inflammation, terminal bronchiole regeneration, alveolar collapse and fibroblastic proliferation. Bronchiolar regeneration was the most peculiar feature seen in the lung with bronchopulmonary dysplasia. Alveolar collapse and interstitial fibroblastic reaction were commonly seen in bronchopulmonary dysplasia. The postnatal age at death was higher in those with bronchopulmonary dysplasia, although the occurrence of the morphologic changes was related with the chronicity of those lesions. These findings suggest that intrauterine infection is an aggravating factor for the neonatal pulmonary injury and bronchopulmonary dysplasia, although the early stage of the lung injury is not a definitive indicator for the progressive pulmonary damage leading to the bronchopulmonary dysplasia.

Classification of Gastrointestinal B-cell Lymphoma and Expression of Cyclin D1, bcl-2, bcl-6, p53 Protein and PCNA.: Ji Han Jung, An Hee Lee, Chang Suk Kang, Byung Kee Kim; Korean J Pathol. 2000;34(6):437-445.

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Abstract PDF: Until recently, the gastrointestinal lymphomas were classified according to the criteria developed for the node-based lymphomas. In recent years, the REAL classification provided a new category of MALT lymphoma and Mantle cell lymphoma in B-cell lymphomas. Low-grade MALT lymphomas have been well characterized clinically, histologically, and immunophenotypically. We retrospectively recategorized 41 cases of the primary gastrointestinal B-cell lymphoma and investigated the expression of cyclin D1, bcl-2, bcl-6, p53 protein, and PCNA by immunohistochemical method. The cases were categorized in 5 groups, low grade MALToma, low/high grade MALToma, high grade MALToma, diffuse large cell lymphoma, and mantle cell lymphoma according to the morphological findings. The expression of cyclin D1 protein was restricted to the cases of mantle cell lymphoma. The bcl-2 protein expression was higher in the low grade MALT lymphoma than in the high grade lymphoma (P=0.006). The bcl-2 protein expression was higher in the low grade area than in the high grade area in the low/high grade MALT lymphoma (P=0.005). The bcl-6 and p53 protein expression was higher in the high grade MALT lymphoma than in the low grade lymphoma (P=0.022, P<0.018). However, the bcl-6 protein expression of the tumor cells was higher in high grade area than in low grade area in the low/high grade MALT lymphoma (P=0.004). The degree of the PCNA expression was positively correlated with the grade of the malignant lymphoma (P=0.003). The above results suggest that the cellular proliferation assessed by PCNA index correlates with the histologic grade. And the bcl-2, bcl-6, p53 protein may be effective in the transition from the low grade MALT lymphoma to the high grade lymphoma. Therefore, we can differentiate the low grade lymphoma from the high grade lymphoma by the immunohistochemical staining for cyclin D1, bcl-2, bcl-6, p53 protein and can predict the prognosis of the patients in accordance with the grade of the tumor.

Expression of Platelet-Derived Growth Factor and Extracellular Matrix in IgA Nephropathy.: Hwal Woong Kim, Kyoung Cheol Moon, So Yeon Park, Hyun Soon Lee; Korean J Pathol. 2000;34(6):446-455.

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Abstract PDF: Glomerulosclerosis represents a pathological hallmark of progressive glomerular injury. Mesangial cell proliferation and accumulation of extracellular matrix (ECM) proteins in the mesangial area frequently precede the formation of glomerulosclerosis. To understand the role of platelet-derived growth factor (PDGF) and ECM in the development of glomerulosclerosis, we examined the expression of type IV collagen, laminin, fibronectin, and PDGF in 45 renal biopsies diagnosed with IgA nephropathy (IgAN) using a standard peroxidase antiperoxidase (PAP) technique. Normal control specimens were obtained from four nephrectomy specimens diagnosed with renal cell carcinoma. As compared with normal controls, type IV collagen increased in 68%, fibronectin in 73%, laminin in 51%, and PDGF in 36% of patients with IgA nephropathy. The staining intensity of PDGF, type IV collagen, and fibronectin increased significantly in cases with moderate to severe mesangial cell proliferation than cases without. In the areas of glomerulosclerosis, the staining intensity of type IV collagen, laminin, and PDGF decreased, whereas that of fibronectin increased. These results suggest that mesangial cell proliferation in relation to increased PDGF expression in IgAN could stimulate the expression of type IV collagen, laminin and fibronectin leading to mesangial expansion. They also suggest that ECM decreased in advanced glomerulosclerosis. Deposition of fibronectin, which originates mainly from the blood stream, increases during the course of progressive glomerulosclerosis, whereas other ECM components decrease in advanced glomeruloslresosis.

Prognostic Implications of Ki-67 Labelling Index and p53, bcl-2 Protein Expression in the Primary Central Nervous System Lymphoma.: Jae Ho Han, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2000;34(6):456-464.

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Abstract PDF: It has been claimed that CNS lymphoma, a rare neoplasm accounting for only a small fraction of malignant brain tumors, occurs with increasing frequency in immunologically normal as well as immunocompromised individuals. We investigated the prognostic value of Ki-67 index, p53, and bcl-2 oncoprotein expression in relation to the clinicopathological parameters in the primary CNS lymphoma patients. The tumors were graded by Kiel classification and the Working formulation and included 33 high-grade, 4 intermediate-grade, and 5 low-grade lymphomas. The phenotype was determined in 38 cases: 30 were B cell type and 8 were T cell type. All cases displayed variable degrees of nuclear Ki-67 staining from 1.0% to 92.0% (mean 51.1%). A highly significant correlation was established between the proportion of Ki-67 positive cells and the classification into grades (p=0.0002) and phenotypes (p=0.0002). Overexpression of p53 and bcl-2 protein was found in 37.1% and 51.4% of 35 patients, respectively. And p53 expression was significantly increased in B cell type (p=0.02). On Kaplan-Meier survival curve, the phenotype, grade of tumors, and p53 and bcl-2 protein expression were not correlated with overall survival. On multivariate analyses, overall survival was independently influenced by Ki-67 index. In conclusion, it is suggested that Ki-67 proliferating index is the most important marker for predicting biologic behavior of the primary CNS lymphoma.

Case Reports

Endobronchial Actinomycosis: A report of two cases.: Hye Seung Han, Kwang Ho Kim, In Seo Park, Jee Young Han, Young Bae Kim, Tae Sook Hwang, Young Chae Chu; Korean J Pathol. 2000;34(6):465-470.

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Abstract PDF: Actinomycosis causes a chronic suppurative infection most commonly involving the cervico-facial region, thorax, and the abdomen. Thoracic infection results from an aspiration of contaminated material from mouth or oropharynx. Actinomyces was known to have a predilection for the periphery of the lung and the endobronchial lesion is extremely rare. We report two cases of actinomycosis presenting as an endobronchial mass which arose in 53-year-old and 44-year-old women. The first case presented with cough, sputum, weight loss and had a history of pulmonary tuberculosis 24 years ago. Chest CT revealed a right lobe collapse simulating mass and suggested carcinoma. The second case presented with hemoptysis for 2 years. Chest CT revealed cystic bronchiectasis of both lungs and intracystic soft tissue mass in the anterior segment of the right upper lobe which suggested aspergilloma. The gross features of them were similar to those of aspergilloma. Characteristic sulphur granules consisting of a granular basophilic center surrounded by a radiating zone of eosinophilic, hyaline, club-shaped projection were histologically confirmed in both cases. Granulomas containing P. westermani eggs were present in the second case. Staphylococcus, true fungal organism, nocardia, and streptomyces shoud be distinguished by analysing their morphologic characteristics in the appropriate stains. Actinomycosis should be included in the differential diagnoses of an endobronchial mass.

Myxoma of the Breast: A case report.: Jung Yeon Kim, Hye Jae Cho, Se Hwan Han; Korean J Pathol. 2000;34(6):471-474.

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Abstract PDF: A case of myxoma of the breast was reported. A 25-year-old woman showed a lump in the left breast which was suddenly enlarged after the delivery of a baby. A tumor measuring 73.53cm was located in the upper outer quadrant of the breast. Fine needle aspiration cytology revealed scattered benign spindle shaped mesenchymal cells with abundant myxoid material. On excision, the tumor was partly solid, partly cystic and multilocular. Each nodule consisted of an abundant mucoid material with a few spindle or stellate mesenchymal cells. Pleomorphism and mitosis were absent. The mesenchymal cells showed immunoreactivities for S-100 protein, smooth muscle actin, and CD34. The myxoid stroma was positively stained with alcian blue and mucicarmine. These findings suggest that constituent cells derive from totipotential primitive mesenchymal cells.

Malignant Granular Cell Tumor of the Shoulder: A case report.: Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee; Korean J Pathol. 2000;34(6):475-479.

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Abstract PDF: A malignant granular cell tumor (MGCT) occurred in the left shoulder of a 62-year-old man. The patient underwent wide marginal excision followed by chemotherapy and radiotherapy. A metastatic tumor was identified in the axillary lymph node 22 months after the excision of the shoulder mass. The primary tumor was a poorly circumscribed mass measuring 5 5 4 cm. On cut section, it was a solid mass with yellowish tan color. Histologically, both primary and metastatic tumor consisted of polygonal cells with abundant granular cytoplasm and a vesicular nucleus with a prominent nucleolus. Two to three mitotic figures per ten high power fields at 200 were counted. Tumor cells were weakly stained with periodic acid-Schiff (PAS) preparation both before and after diastase digestion, and were positive for S-100 protein, neuron-specific enolase (NSE), and vimentin. By electron microscopy, the cytoplasm was filled with numerous autophagolysosomes containing myelin figures, mitochondria, and fragmented rough endoplasmic reticula. Basal laminae and angulated bodies were also noted. These findings suggest schwannian differentiation of this tumor.

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