Journal of Pathology and Translational Medicine

Volume 32(9); September 1998

Original Articles

Sequential Changes of Extracellular Matrix mRNA in Anti-GBM Antibody Induced Crescentic Glomerulonephritis in the Rabbit.: Moon Hyang Park, Unn Wha Lee, In Sup Han, Rho Won Chun, Jung Woo Noh; Korean J Pathol. 1998;32(9):627-637.

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Abstract: Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency, however, the mechanism regarding renal fibrosis in renal injury is not well understood. Recently, several kinds of cytokines have been known to be related to fibrosis after renal injury. The interaction between elements regulating fibrogenesis would be better understood by looking at the effect of TGF-beta1 on the synthesis and accumulation of extracellular matrix, especially collagenous proteins. Crescentic glomerulonephritis (CGN) was induced in New Zealand White rabbits by administration of guinea pig anti-GBM IgG after sensitization with guinea pig IgG; and their kidneys were analyzed for the development of crescents and fibrosis through sequential renal biopsies. Serum creatinine levels in a time course progressively increased until day 15. We semi-quantitatively assayed the levels of the expression of alpha1(I) collagen mRNA and TGF-beta1 mRNA factored for GAPDH mRNA using RT-PCR. We observed a progressive interstitial fibrosis and the expression of collagen I both in the cortex and medulla. The effect of repeated renal biopsy itself on pathology and on the expression of alpha1(I) collagen mRNA and TGF-beta1 mRNA in a time course were not significant, but a very mild increase of the expression of alpha1(I) collagen mRNA was noted at day 15. Histology showed a progressive crescent formation and interstitial fibrosis in a time course that roughly paralleled the expression of alpha1(I) collagen mRNA in both cortex and medulla. TGF-beta1 mRNA was hardly expressed at day 0 in cortex as well as in medulla. It was elevated from day 1, peaked at day 7, and then decreased. In medulla, TGF-beta1 mRNA was noticeably expressed at day 1, peaked at day 4, and then decreased. The expression of alpha1(I) collagen mRNA was seen even before inducing CGN. It was gradually and continuously increased until day 15 both in cortex and medulla. These results suggest that the expression of TGF-beta1 mRNA precedes that of alpha1(I) collagen mRNA in the early stage of CGN and has a central role for provoking the accumulation the collagen I, the most representative interstitial extracellular matrix, in the rabbit model CGN induced by anti-GBM antibody. We conclude that the measurement of the expression of TGF-beta1 mRNA and/or alpha1(I) collagen mRNA in a biopsy sample can be a useful predictor for renal outcome.

Deletion within LMP-1 Oncogene in Hodgkin's Disease in Korea.: Ghee Young Kwon, Woo Sung Ahn, Bo Young Lee, Seung Sook Lee, Jooryung Huh, Chul Woo Kim; Korean J Pathol. 1998;32(9):638-646.

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Abstract: LMP (latent membrane protein)-1 protein is one of the Epstein-Barr viral proteins and it is the most crucial one for the transforming activity. It is known to show considerable variation in its nucleic acid sequence and some biologic difference is reported to be associated with the variation. Twenty four cases of the EBV-associated Hodgkin's disease cases were searched for the 30-bp deletion within the C terminal intracytoplasmic domain of LMP-1 oncogene, one of the well-known genetic variation, by PCR and Southern blot using selected sets of primers and probes. The strain of the virus was also determined with PCR. Each case was positive both on LMP-1 immunostaining and in situ hybridization for EBER (Epstein-Barr encoded RNA). Deletion within LMP-1 oncogene was identified in 22 cases (92%), of which 5 cases showed wild form as well as a deleted form of LMP-1 at the same specimens. In seven cases showing the non-deleted form, pure or mixed with a deleted form, the distribution of sex and age was similar to that of the deleted form-only-group, but there was a slight tendency for a higher stage at presentation (4 of the 7 cases presented with stage IV). Those seven cases comprised of 4 cases of nodular sclerosis (NS), 2 cases of mixed cellularity (MC) and a case of lymphocyte depletion subtype while there were 9 and 12 cases of NS and MC among all the examined cases, respectively. Two cases with both a deleted form and the non-deleted form of LMP-1 showed type I and II strain of the virus while all the others contained only type of the. In conclusion, the rate of deletion in LMP-1 oncogene in our series was higher than that reported in western countries and there was a slight tendency for higher stages in cases detecting mixed deleted and non-deleted forms of LMP-1 than in cases a of deleted from of LMP-1.

Expression of Transforming Growth Factor-beta1 and Its Effects on the Extracellular Matrix Formation and Angiogenesis in Gastric Carcinoma.: Young Hee Choi, Young Euy Park; Korean J Pathol. 1998;32(9):647-654.

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Abstract: Malignant cells in culture express elevated levels of transforming growth factor-beta1 (TGF-beta1) mRNA and secrete an abundant amount of the TGF-beta1 protein. An attempt was made to define the role of the TGF-beta1 secreted from tumor cells, as a possible humoral factor which functions in a paracrine manner to stimulate the production of collagen and angiogenesis in gastric carcinoma. The expression of the TGF-beta1 by immunohistochemical stain (n=70) in gastric adenocarcinoma tissues was studied. Angiogenesis was evaluated by immunohistochemical staining of tumor vessels, using polyclonal antibody to factor VIII related antigen and counting the three most active areas of neovascularization. The extracellular matrix was counted as area density by using an image analyzer following Masson-Trichrome staining. The prominent reactivity for TGF-beta1 was associated with invasion depth (r=0.2, p<0.05), increased number of microvessel (r=0.49, p<0.05) and increased area density of extracellular matrix (r=0.36, p<0.05), respectively. In summary, TGF-beta1 may have a role in tumor invasion and metastasis by increased angiogenesis and deposits of extracellular matrix.

Expression of Cell Adhesion Molecules -CD44H and CD44v6- in Colorectal Carcinoma.: Dae Cheol Kim, Seo Hee Rha, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1998;32(9):655-662.

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Abstract: During tumor progression, a subset of cells acquires metastatic properties, presumably through a series of genetic alterations. As the result, cells detach from the primary tumor, penetrate the basement membrane and invade the adjacent structures including lymph and blood vessels. Loss of adhesive functions and gain of new adhesive functions are thought to play a crucial role in this metastatic cascade. Since tumor metastasis is the principle cause of death for cancer patients including colon cancer, there is a consensus that a search for tools that allow effective assessment of the metastatic potential of tumors is a prime goal for cancer research. An immunohistochemical study of cell adhesion molecules, CD44H and its variant CD44v6, was done to evaluate their relationship with known prognostic factors related to the progression and metastasis of colorectal carcinoma in 94 cases of colorectal carcinoma tissues. The results were as follows. The CD44H expression was detected in 90 (95.7%) and CD44v6 in 53 (56.4%) out of 94 cases of colorectal carcinoma, and the CD44H was overexpressed in tumor tissue more than in normal mucosa in 62% of the cases. The expression rates of both protein were not significantly correlated with age and sex of the patients, invasion depth, lymph node metastasis, tumor differentiation, and tumor site. The coexpression of CD44H and CD44v6 in tumor was significant (p<0.05). The above results suggest that overexpression of CD44H and loss of function to control the alternative splicing of CD44 mRNA resulting in CD44v6 expression and alteration of adhesive function are closely associated with tumorigenesis of the colorectum.

Relationship between Vimentin Expression and Progression of Uterine Cervix Epithelial Neoplasms.: Sung Chul Lim, Keun Hong Kee, Hyun Jong Park; Korean J Pathol. 1998;32(9):663-669.

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Abstract: Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but the evidence of the aberrant expression of vimentin in epithelial cancer cells suggests that the vimentin expression might be related to local invasiveness and metastatic potential. There have been a few previous studies on the vimentin expression in human cervical carcinogenesis using in vivo and in vitro models. We examined the immunohistochemical vimentin expression in various squamous epithelial neoplasms of the uterine cervix, including the cervical intraepithelial neoplasia group (n=25), the microinvasive squamous cell carcinoma group (n=15), the invasive squamous cell carcinoma group (n=15) and the metastatic squamous cell carcinoma group (n=8). Vimentin positivity was significantly higher in the invasive than in the intraepithelial group, and in the cases with lymph node metastasis than in those without metastasis, suggesting a relationship between the vimentin expression and progression of the uterine cervical epithelial tumors.

Primary Central Nervous System Lymphomas; A Clinicopathologic Study of 18 Cases.: Yu Kyung Jeong, Young Hyeh Ko, Dong Kyu Na, Yeon Lim Suh, Sang Yong Song, Dae Shik Kim, Mi Kyung Kim, Howe Jung Ree; Korean J Pathol. 1998;32(9):670-679.

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Abstract: The incidence of a primary central nervous system (CNS) lymphoma in western countries is about 1% of all the intracranial tumors and has increased 2.2% over the last decade. A similar pattern of increased frequency is observed in Korea. Although most CNS lymphomas in western countries are high grade tumors carrying poor prognosis, the clinicopathologic features of the Korean CNS lymphoma have not been well studied. We report clinicopathological features of 18 cases of histologically proven primary brain lymphoma. The mean age of the patients was 50 years and there was no sex difference. The clinical and radiological characteristics included multiple site of occurrence, infrequent extracranial spread, and frequent seeding via cerebrospinal fluid. No patients were immune-compromised host. Of 18 cases, 15 cases were of B-lineage and 2 cases were of T-lineage. According to REAL classification, there were 12 cases of diffuse large B cell lymphoma, two cases of B cell lymphomas of small lymphoid cell, and two cases of peripheral T cell lymphoma, unspecified. The remaining subtypes were not subclassified because of inadequate material. Pleomorphic cytologic features and necrosis of varying extent were frequent in the cases of diffuse large B-cell lymphoma. These results suggest that overall clinicopathologic features of primary malignant lymphomas of the central nervous system in Korea are similar to those of western countries.

Case Reports

Lymphoepithelioma-like Carcinomas of the Stomach Report of 4 cases associated with Epstein-Barr virus.: Eun Sook Nam, Duck Hwan Kim, Hye Kyung Ahn, Hyung Sik Shin, Young Sik Kim, Han Kyum Kim, Insun Kim; Korean J Pathol. 1998;32(9):680-686.

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Abstract: Lymphoepithelioma-like carcinoma (LELC) that histologically resembles nasopharyngeal lymphoepithelioma has been reported in various sites including the stomach, salivary gland, lung, skin, thymus, tonsil and uterine cervix. LELC of the stomach was rarely reported after the first report by Burke et al. in 1990. More than 60% of them were associated with Epstein-Barr virus (EBV). Most commonly affecting elderly Asians with slight male predominance (M/F ; 1.2/1), it usually is located in the proximal portion of the stomach and distinguished from lymphoid-rich adenocarcinoma by the absence of definitive glandular differentiation in the LELC. We recently experienced 4 cases of LELC of the stomach associated with EBV. Patients consisted of two Korean females and two Korean males with one in 3rd decade, one in 5th decade and two in 6th decade. The tumors of all cases were located in the proximal portion of the stomach. Gross types were 1 Borrman type I, 2 Borrman type II and 1 early gastric carcinoma type IIc. The size of the tumors varied from 0.8 cm to 7 cm. Microscopic findings were similar in all 4 tumors.; The tumors were composed of syncytial nests of undifferentiated cells having vesicular nuclei with prominent nucleoli, admixed with abundant lymphoplasma cell infiltration in the stroma. Immunohistochemical staining revealed that the tumor cells were reactive for cytokeratin and the stromal lymphocytes were mostly T cells. There were dark hybridization signals in the nuclei of most of the tumor cells but no signals in the stromal lymphocytes in three cases on in situ PCR hybridization and on all cases PCR amplification for EBNA-1. It is concluded that LELCs of the stomach have distinctive histologic characteristics and the usual association with EBV. Further accumulation of these cases will define the prognosis.

Retroperitoneal Duplication Cyst Associated with Heterotopic Pancreas: A case report.: So Yeong Oh, Myoung Ja Chung, Dong Geun Lee, Ho Yeul Choi; Korean J Pathol. 1998;32(9):687-690.

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Abstract: Occurrence of a retroperitoneal duplication cyst associated with a heterotopic pancreas is rare. We report a case of a retroperitoneal duplication cyst associated with a heterotopic pancreas. A 35-year-old male was admitted, presenting with back pain. A pelvic computed tomographic scan disclosed a 10 cm-sized cystic mass filling the lower pelvis and displacing the rectosigmoid colon anteriorly. Histologically, the cyst wall was lined partly by mucin-secreting columnar epithelium, showing atypical hyperplasia and partly by a gastric fundic-type and a colonic-like mucosa. Beneath the epithelium, organized bundles of smooth muscle were arranged in two layers analogous to smooth muscles layers of the bowel and a small piece of pancreatic tissue were present in the smooth muscle wall of the cyst.

Mineralizing Pulmonary Elastosis Associated with a Giant Cell Carcinoma.: Min Kyung Kim, Kwang Il Kim, Min Joo Kim, Young Woo Suh, Il Hun Seo, Hyun Ju Lee, Han Gyeom Kim; Korean J Pathol. 1998;32(9):691-693.

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Abstract: Mineralizing pulmonary elastosis is a result of chronic alveolar hemorrhage forming iron encrustation of a pulmonary elastic tissue. It has been reported as a complication of some diseases such as bronchiectasis, idiopathic pulmonary hemosiderosis, and cardiac failure. It is extremely rare to occur with a giant cell carcinoma as we experienced. A 59 year-old man visited our hospital for cough and blood tinged sputum. A chest CT scan revealed 10 9 6 cm sized round mass in the left upper lobe. He had lobectomy of left upper lobe, but died of respiratory failure at the postoperative eighteenth day. The lung showed a necrotic tumor and a yellow tan consolidation around the mass. Microscopically, the tumor was composed of nests or syncytia of large bizarre cells and tumor giant cells, and was diagnosed as a giant cell carcinoma. Interestingly, in the surrounding lung parenchyma there were a lot of foreign body type giant cells phagocytizing iron encrustated elastic fibers, which were easily identified by elastic van Gieson and prussian blue stains. Those degenerated elastic fibers appeared in pulmonary interstitial tissue as well as blood vessel walls. The authors concluded tumoral hemorrhage and necrosis resulted in mineralizing pulmonary elastosis.

Primary Malignant Melanoma of the Esophagus: A case report.: Lee So Maeng, Kyoung Mee Kim, Eun Jung Lee, Anhi Lee, Sang In Shim; Korean J Pathol. 1998;32(9):694-696.

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Abstract: This report presents an unusual case of primary malignant melanoma in the midesophagus. The patient was a 36-year-old woman presenting with dysphagia and odynophagia. The resected esophagus and proximal stomach showed a dark purple large polypoid mass, measuring 6.0 3.3 2.0 cm, with a diffuse tan pigmentation of surrounding mucosa in the mid-esophagus and two small daughter nodules, up to 1.2 0.3 cm, in the lower esophagus near the gastro-esophageal junction. A microscopic examination revealed a malignant melanoma of epithelioid cell type confined to mucosa and submucosa with a diffuse melanosis. Cytoplasmic immunoreactivity for HMB 45 and S-100 protein were noted. An electron microscopic examination revealed large, loosely cohesive variable shaped cells with a few cytoplasmic premelanosomes.

Well-Differentiated Papillary Mesothelioma of the Peritoneum: A case report .: Yi Kyeong Chun, Yee Jeong Kim, Sung Ran Hong; Korean J Pathol. 1998;32(9):697-699.

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Abstract: Well-differentiated papillary mesothelioma (WDPM) of the peritoneum is considered to be a distinct subtype of peritoneal mesothelioma and has mostly behaved in a benign fashion. We report a case of WDPM in a 48-year-old-woman. It was incidentally found during a hysterectomy for a uterine cervical carcinoma. Grossly, the tumor was composed of multiple peritoneal nodules, measuring up to 2 cm. Microscopically, the nodules showed well-developed papillae lined by a single layer of cuboidal mesothelial cells. Immunohistochemical staining revealed a positive reaction for cytokeratin and a negative reacion for carcinoembryonic antigen and Leu-M1. Ultrastructurally, the tumor cells showed numerous long, slender microvilli and desmosomes.

Epithelioid Leiomyosarcoma of Skin: A case report.: Han Seong Kim, Nam Bok Cho, Hyun Soon Lee, Kye Yong Song; Korean J Pathol. 1998;32(9):700-703.

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Abstract: This report concerns a rare malignant smooth muscle neoplasm of the skin and the subcutaneous tissue, which was examined immunohistochemically and ultrastructurally. It occured in a 48-year-old female patient who had suffered from painful nodules on the left shoulder. The nodules were removed and diagnosed as a benign fibrohistiocytic tumor. One year after local excision, multiple nodules were detected by physical examination at the previous operation site. Grossly, thirteen well-defined small nodules had spread in the dermis and the subcutaneous tissue, of which nine were located from lower dermis to the subcutaneous tissue and four were in the subcutaneous tissue. Histologically, each nodule consisted mainly of epithelioid tumor cells having eosinophilic or clear plump cytoplasm and round to oval nuclei with small nucleoli, and some peripheral spindle tumor cells. The tumor cells were negative for PAS reaction with and without diastase digestion or alcian blue. Immunohistochemically, tumor cells were positive for smooth muscle actin and vimentin. Ultrastructurally, the tumor cells showed actin filaments and dense bodies in cytoplasm. This case was diagnosed as an epithelioid leiomyosarcoma of the skin and the subcutaneous tissue with local metastasis one year after local excision.

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