Journal of Pathology and Translational Medicine

Volume 33(2); February 1999

Original Articles

The Effects of Transforming Growth Factor beta1 on Apoptosis in Rat Hepatocellular Carcinoma.: Young Euy Park, Young Hee Choi, Won Yo Lee, Jin Ja Park, Kyung Chan Choi, Hyung Shik Shin; Korean J Pathol. 1999;33(2):71-79.

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Abstract: Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.

Expression of E-cadherin and p53 Proteins in Gastric Adenocarcinoma.: Sook Hee Hong, Mee Sook Roh; Korean J Pathol. 1999;33(2):80-87.

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Abstract: The gastric carcinoma shows various molecular and genetic alterations in its development and progression. There are evidences that the changes of the expression of cell adhesion molecules affect the morphogenesis of the tumor as well as the tumor progression and metastasis. The purpose of this study is the evaluation of the expression pattern of a cell adhesion molecule, E-cadherin, and a tumor suppression gene, p53, by immunohistochemical stain and the relationship of their expressions with clinicopathologic findings in gastric adenocarcinoma tissue. The E-cadherin expression was absent or reduced in 93 cases (73.2%) and p53 was positive in 98 cases (77.2%) of 127 gastric adenocarcinomas. The frequency of reduced E-cadherin expression was significantly higher in poorly differentiated adenocarcinomas (p=0.04) and in diffuse type (p=0.01), but that of p53 positivity was not significantly correlated with tumor differentiation. Both proteins showed no correlation with depth of invasion, lymph node and distant metastasis, and tumor stage. There was no correlation between E-cadherin and p53 expression. This study indicates that the altered expressions of E-cadherin and p53 are associated with the development of intestinal and diffuse types of gastric adenocarcinoma and the differentiation of the gastric adenocarcinoma is affected by cell adhesion mediated by E-cadherin, but the modes of tumor progression and metastasis are not affected by E-cadherin and p53.

The Expression of p53, c-erbB-2 and nm23 Proteins in Breast Cancer.: Kyo Young Lee, Yong Goo Kim, Young Shin Kim, Kyung Ja Han, Chang Suk Kang, Jean A Kim, Won Il Kim, Sang In Shim; Korean J Pathol. 1999;33(2):88-95.

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Abstract: Recently, p53, c-erbB-2 and nm23 proteins have been studied in breast cancer. The expression of p53 protein indicates the mutation of p53 gene known as a tumor supressor gene, and c-erbB-2 gene amplification has been considered an indicator of poor prognosis and nm23 a metastsis suppressor gene. In order to elucidate the roles and relations of these proteins in the develpoment, progression and metastasis in breast cancer, we studied 89 cases of invasive breast cancer and 32 cases of lymph node metastasis for the expression of p53, c-erbB-2 and nm23 proteins using an immunohistochemical method. The results were as follows: 1) The expression rates of p53, c-erbB-2, and nm23 proteins in breast cancer were 40.4%, 34.8% and 55.1%, respectively. Co-expression of p53 protein and c-erbB-2 protein was found in 20.2% of cases, showing the highest incidence in poorly differentiated type (40%). 2) p53 protein expression was increased in poorly differentiated type but was not statistically significant. On the other hand, the expression of nm23 protein was decreased in poorly differentiated type, which was statistically significant (p<0.05). 3) The correlation of p53 protein expression with c-erbB-2 protein expression was statistically significant (p<0.05) but that with nm23 protein was not. 4) In the cases with lymph node metastasis, discordant expression of p53, c-erbB-2 and nm23 proteins between primary tumor and the lymph node metastatic tumor was found in 9.4%, 3.1% and 18.8% of cases, respectively. The above results suggest that overexpression of p53 and c-erbB-2 proteins and downregulation of nm23 protein are associated with the tumor progression in the breast cancer.

VEGF Expression and Angiogenesis in Uterine Cervical Carcinomas.: Jin Sook Lee, Kang Suek Suh; Korean J Pathol. 1999;33(2):96-102.

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Abstract: Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms responsible for angiogenesis in uterine cervical neoplasia are not well defined. To determine the relationship between angiogenesis and the expression of vascular endothelial growth factor (VEGF) in the cervical neoplasia, the author studied 63 cases of the cervical neoplasia diagnosed between the years 1993 to 1997 at Pusan National University Hospital. The expression of VEGF was semiquantitatively analyzed in paraffin sections by immunohistochemical method. Histologic sections immunostained for factor VIII-related antigen were evaluated for microvessel density. Increased expression of VEGF and microvessel counts was significantly correlated with depth of invasion. Increased microvessel counts were also significantly associated with increased VEGF expression. These results suggest that VEGF is an important angiogenic factor and associated with progression of the cervical neoplasia.

AgNOR Counts in S-phase Human Cells.: Seung Il Kim, Eun Jung Lee; Korean J Pathol. 1999;33(2):103-107.

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Abstract: The nucleolus of human cell is a morphologically well recognizable nuclear organelle and the argyrophilic NORs (AgNORs) are nucleic acid-argyrophilic nonhistone protein complex in the nucleoli and the silver staining allows their identification and enumeration at the light microscopic level. The AgNOR counts are in parallel with mitotic activity and vary in different phase of cell cycle. It has been reported that human cells have one AgNOR during interphase and S-phase. However, the correlation between the number of AgNORs and S-phase markers is still controversial and they have never been studied simultaneously. In this study, AgNOR and PCNA were stained simultaneously to find out the relationship of AgNOR counts with cell cycle (S-phase) in human palatine tonsil, gastric carcinoma, liver and brain tissues. S-phase cells (PCNA-positive) were found predominantly in lymphoid follicles in palatine tonsil but gastric carcinoma showed diffuse immunoreactivity for PCNA. The AgNOR counts varied according to the type and locus of tissue. More than one AgNOR were identified in S-phase cells and some of hepatocytes and neurons in the brain which were not in S-phase contained two or more AgNORs. The above results suggest that the number of AgNOR is a characteristic feature of each type of cells and can be more than one even in S-phase.

Extrapleural Solitary Fibrous Tumor A clinical & pathological study of 8 cases.: Mi Kyung Lee, Dong Hwan Shin, Min Sun Cho, Yuon Mee Kim, Jin Kim; Korean J Pathol. 1999;33(2):108-114.

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Abstract: We reviewed eight solitary fibrous tumors occurring at sites other than pleura (three orbit, two retroperitoneum, one each hard palate, thyroid, and tongue) which shared the histologic and immunohistochemical features of solitary fibrous tumors of pleura. Six patients were women, and two were men, aged from 26 to 74 years. The tumors ranging from 1.5 to 19 cm in diameter presented as well-circumscribed, unencapsulated, soft to rubbery tissue masses. Histologically they were characterized by a proliferation of spindle or ovoid cells intervened by a dense bundles of collagen. A variety of growth patterns was identified but the so-called patternless pattern was the predominant one. One tumor exhibited highly cellular sarcomatous areas with extensive necrosis, which was diagnosed as malignant solitary fibrous tumor. Immunohistochemical studies showed that all of the tumors were strongly positive for both CD34 and vimentin, but negative for cytokeratin, S-100 protein, EMA, and desmin. One case examined ultrastructurally showed features of fibroblast. All but one showed no evidence of recurrence or metastasis over follow-up period of 14 to 32 months. We conclude that extrapleural solitary fibrous tumors represent a distinct mesenchymal tumor with variable histologic features and should be differentiated from other spindle cell mesenchymal tumors.

Solitary Fibrous Tumor A clinicopathologic review of five cases.: Bum Kyung Kim, Dong Wook Kang, Kyeong Hee Kim, Seong Ki Min, Jin Man Kim, Kyu Sang Song, Dae Yung Kang, Si Whan Choi; Korean J Pathol. 1999;33(2):115-120.

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Abstract: We experienced five cases of solitary fibrous tumor; two in the pleura, two in the orbital soft tissue, and one in the lung parenchyma. Three patients were male, and the age of the patients ranged from 38 to 71 years (mean age: 53.6). Grossly, the masses were well circumscribed and had varying sizes from 2.5 to 30.0 cm. The cut surfaces were grayish-yellow firm with focal variegated hemorrhage, necrosis, cystic change, and myxoid area. Microscopically, these were characterized by a haphazard proliferation of spindle cells or polygonal cells separated by variable amounts of hyalinized collagen and showed a prominent vascular channels reminiscent of hemangiopericytoma in foci. Immunoperoxidase stains showed a strong reactivity for CD34, and were weakly positive for vimentin. Electron microscopical examination revealed features of fibroblast; spindle to round tumor cells were arranged in groups and surrounded by collagen. Nucleoli were seldom prominent. The cytoplasm contained many microfilaments and a moderate number of cisternae of rough endoplasmic reticulum.

Cryptosporidium Infection of Human Intestine: An Electron Microscopic Observation.: Min Suk Kim, Yun Kyung Kang, Chul Jong Yoon, Mee Joo, Hye Kyung Lee, Jeong Gi Seo, Je G Chi; Korean J Pathol. 1999;33(2):121-127.

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Abstract: Protozoa of the genus Cryptosporidium are small coccidian parasite known to infect the mucosal epithelium of a variety of animals including human, causing fatal course in immunodeficient patients as well as self-limited illness in healthy individuals. Various life cycle stages including trophozoite, meront, merozoite, gametocyte and oocyst in infected mucosa are a diagnostic feature. Electron microscopy (EM) provides sufficient findings for genus and species identification of this parasitic organism. The authors presented scanning and transmission EM findings of Cryptosporidium parvum infection in two children: one with acute lymphoblastic leukemia and the other without any evidence of immune compromise.

Case Reports

Sarcomatoid Transitional Cell Carcinoma of the Renal Pelvis A report of two cases.: Kyo Young Lee, Mi seon Kwon, Yeong Jin Choi, Chang Suk Kang, Seok Jin Kang, Baying Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(2):128-132.

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Abstract: Sarcomatoid carcinomas are malignant epithelial neoplasms in which the tumor cells assume a partial or complete spindle cell pattern of growth, leading to the erroneous classification of some true carcinomas as sarcomas. These spindle cells are malignant and manifest various amount of both vimentin and cytokeratin. Positive reaction of some of the spindle cells for cytokeratin antibodies is confirmatory. Clinical features do not differ significantly from those of patients with high-grade transitional cell carcinoma. So far, 13 cases of sarcomatoid transitional cell carcinoma of the renal pelvis have been reported in English and Korean literature. In this report, we describe clinicopathologic features of recently observed two cases of sarcomatoid transitional cell carcinoma of the renal pelvis and summarize the pathologic findings of previously reported cases with review of the literature.

Liesegang Structure in Simple Hemorrhagic Cyst Incidentally Found in Donor Kidney: A case report.: Dong Hoon Kim, Moon Hyang Park; Korean J Pathol. 1999;33(2):133-136.

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Abstract: Liesegang rings (LRs) are peculiar structure of periodic precipitation zones from supersaturated solution in colloidal system. LRs are formed by a process referred to as "the Liesegang phenomenon". Here we describe LRs in renal hemorrhagic cyst from the donor kidney of a 59-year-old man. His general condition was good. Abdominal ultrasonography revealed a simple cyst in the left kidney. After donor nephrectomy for renal transplantation, a 3x2 cm sized cyst containing the brownish necrotic fluid was noted in the upper pole of left kidney. Frozen section from the relatively thickened cystic wall was performed. During frozen section examination, round concentric rings with double-layered outer wall, striations and amorphous central nidus admixed with the foamy macrophages were found and the lesion was originally interpreted as xanthogranulomatous inflammation with unusual crystalline structures in the cytoplasm of macrophages or freely in the interstitium. Macrophages with calcium crystals or malakoplakia were also considered at that time. Additional specimen for the permanent sections showed a simple hemorrhagic renal cyst with areas of small or large aggregates of LRs along the cyst wall. Multiple round ring-like structures ranging from 11 to 42 micrometer in diameter had uniform, pale eosinophilic, radially striated double wall. Histochemical and immunohistochemical stainings for iron, calcium, mucopolysaccharide, amyloid, cytokeratin were negative in these structures. They were highlighted by CD68 immunostaining as well as PAS and Masson's trichrome stainings. Awareness of Liesegang phenomenon in cystic lesions will decrease the possibility of erroneous diagnosis as another type of pathologic process, such as parasitic worms or eggs.

Intraductal Cystic Hypersecretory Carcinoma of the Breast: A case report.: Jin Haeng Chung, Seung Sook Lee, Jae Soo Koh, Kyung Ja Cho, Jong Inn Lee; Korean J Pathol. 1999;33(2):137-140.

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Abstract: The cystic hypersecretory duct carcinoma of the breast was first described in 1984 by Rosen and Scott and warrants separate discussion because of its unusual pathological features. It is morphologically distinguishable from juvenile (secretory) carcinoma and from mucinous (colloid) carcinoma or mucocele-like tumor. We present a case report of intraductal cystic hypersecretory carcinoma of the breast with hormone receptor and oncogene study. The histologic differential diagnosis, with an emphasis on benign lesions that may have a predominant cystic component, is also discussed.

Epithelioid Leiomyosarcoma of Retroperitoneum: A case report.: Myeng Sun Park, Ji Young Seo, Hae Jin Jeong, Bang Hur, Man Ha Hur; Korean J Pathol. 1999;33(2):141-144.

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Abstract: Epithelioid smooth muscle tumor is relatively rare and potentially malignant, especially in retroperitoneum. Distinct criteria for malignancy still have not been clarified in this epithelioid variant arising in retroperitoneum. We report a deceptively benign-appearing epithelioid leiomyosarcoma in a 50-year-old female. She was admitted with abdominal discomfort and dysuria. Abdominal CT showed a well-demarcated, 10 10 cm sized, solid mass in retroperitoneum. Concomitant metastatic lesions were noted in right lung field. Surgical excision of retroperitoneal mass and right lung lobectomy were performed. The retroperitoneal mass showed yellowish-tan, well-delineated and lobulated appearance. Histologically, this tumor was composed of predominantly epithelioid, round to oval cells with distinct clear cytoplasm and slightly atypical nuclei. Mitosis was rare (0~1/50 HPF). Lung lesions were morphologically similar to that of retroperitoneum.

B-cell Prolymphocytic Leukemia Involving Entire Female Genital Tract: A case report.: Hee Jung Lee, Young Shin Kim, Yong Gu Kim, Kyung Ja Han, Kyo Young Lee, Chang Suk Kang, Sang In Shim, Jong Wook Lee, Woong Shick Ahn, Soo Pyung Aim, Seung Il Kim; Korean J Pathol. 1999;33(2):145-148.

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Abstract: Prolymphocytic leukemia is a chronic lymphoproliferative disorder, characterized by prominent splenomegaly, prolymphocytes accounting for more than 55% of circulating lymphocytes, no significant peripheral lymphadenopathy and short term survival with terminal fatal multi-organ failure. We report a case of B-cell prolymphocytic leukemia in a 57-year-old woman who presented with easy bruising and arthritis for 1 year and low abdominal pain for 2 months. Physical examination revealed gingival hypertrophy and mild splenomegaly. On peripheral blood smears the leukocytes were markedly increased in number due to leukemic cells that count about 62% of leukocytes. The bone marrow aspiration smear and biopsy revealed diffuse infiltration of medium to large prolymphocytes having moderate amount of basophilic cytoplasm, round to oval nuclei with coarse chromatin, and prominent nucleoli. Abdominal pain aggravated despite chemotherapy, and pelvic computed tomography (CT) revealed a huge lobular pelvic mass which had increased in size on the follow-up CT. Total hysterectomy with bilateral adnexectomy was performed. Microscopic findings included massive infiltration of prolymphocytic cells in the uterus, upper vaginal wall, bilateral ovaries, and bilateral mesosalpinges. On immunohistochemistry, the leukemic cells showed B cell gamma light chain phenotype.

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