Journal of Pathology and Translational Medicine

Volume 29(6); December 1995

Original Articles

Expression Patterns of Bcl-2 and PCNA in Cervical Intraepithelial Neoplasia.: Mee Sook Roh, Gi Yeung Huh, Sook Hee Hong; Korean J Pathol. 1995;29(6):703-713.

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Abstract PDF: Immunohistochemical stains for bcl-2 oncoprotein and PCNA and examination of the mitosis level were perfon-ned in 76 cases of cervical intraepithelial neoplasia (CIN). We studied the expression pattern of bcl-2 protein according to histologic grades and the function of bcl-2 oncogene associated with cellular proliferation by comparing with PCNA expression and the mitosis level. The results were as follows: 1) Of 76 cervical intraepithelial neoplasias, 23 (30.3%) were CIN I, 23 (30.3%) were CIN II, and 30 (39.4%) were CIN III. 2) Of 23 CIN I cases, grade 0 and 1 mitosis level were seen in 20 (87.0%), PCNA in 16 (69.6%), and bcl-2 in 19 (82.6%) cases, respectively, which indicates that CIN I lesions have a low cellular proliferative activity. 3) Of 30 CIN III cases, grade 2 and 3 mitosis level were noted in 28 (93.3%), PCNA in 25 (83.3%) and bcl-2 in 19 (63.3%) cases, respectively, which indicates that CIN III lesions have a high cellular proliferative activity. The results suggest that progressive increase of dysfunctional proliferative activity and abnormal decrease of cell death result in increased number of neoplastic cells according to CIN grade. Also the expression rate of bcl-2, PCNA and mitosis level were significantly different between CIN I and 111, which suggest that they might be good parameters for classifying CIN into low and high grade and for prediction of the biologic behavior of the CIN lesion.

Ultrastructural Changes in Human Gallbladder Epithelium in Acalculous and Calculous Cholecystitis.: Sung Chul Lim, Chae Hong Suh; Korean J Pathol. 1995;29(6):714-726.

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Abstract PDF: Cholelithiasis is defined as the presence of stones within the lumen of the gallbladder or in the extrahepatic biliary tree. Cholecystitis, secondary to gallstones, is a common surgical disorder in Korea. Detailed microscopic descriptions, particularly the ultrastructural changes, of these diseases were not available. The goal of this study was to identify the ultrastructural alterations of gallbladder epithelium in cholecystitis with and without a stone, according to the degree of severity of inflammation, and the nature of the stone. The gallbladders of the control group, and cholecystitis cases without stone and with stone were fixed and examined with routine stain, special stain, immunohistochemical stain and trans-mission electron microscopy. The number and the volume density of the mucin containing secretary granules were not significantly increased in the calculous cholecystitis cases compared with those of the acalculous cholecystitis cases. Major findings were that the calculous cholecystitis cases showed a markedly reduced total lysosome area and volume density of the lysosome compared with those of the acalculous chole-cystitis cases. The differences between the mucin secretary granules and lysosomes, according to the degree of severity of cholecystitis and the natures of gallstones, were statistically not significant.

Immunohistochemical Study of the Expression of p53, Pan-ras, c-erbB-2 and PCNA in N-Nitrosomorpholine(NNM)-Induced Hepatocellular Carcinoma of Rats.: Ok Kyung Kim, Ryun Jo Shin; Korean J Pathol. 1995;29(6):727-739.

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Abstract PDF: The focus of this study was o aialyze the morphologic expression of p53, Pan-ras, c-erbB-2, and PCNA in preneoplastic and neoplastic liver lesions induced with NNM of rats. The development of hepatocellular tumors was investigated by histology and electron microscope in 65 Splague-Dawley rats administered with NNM in drinking water at low dose(5 mg/100 ml) and high dose(20 mg/100 ml). Three types of hepatocytic degeneration glycogenotic, eosinophilic and basophilic changes were followed by the appearance of hepatocellullar carcinoma. Hepatocellular carcinoma was increased in number and size according to NNM dosage and to duration of exposure. The histological classifications of hepatocelular carcinoma wer trabecular type, which was which was the most common, large eosinophilic, small cell, adenocarcinomatous and clear cell type. The expression of p53, Pan-ras, c-erbB-2 PCNA was examined by immunohistochemical stains. Eosinophilic degeneration revealed mild positivity at 18-26 weeks for expression of all oncogenic proteins studied and PCNA, whereas precancerous lesions showed variable expression from negative to moderate positivity on PCNA. Hepatocellular carcinoma lesions showed strong positivity for all stains and increased intensity during experimental period. These may indicate that chemical carcinogen produce hepatic eosinophilic degeneration and preCancerOus lesions by genetic mutation, resulting in hepatocellular carcinoma.

Correlation between Tumor Angiogenesis and Metastasis in Invasive Breast Carcinoma.: Nam Hoon Kim, Moon Hyang Park; Korean J Pathol. 1995;29(6):740-745.

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Abstract PDF: Tumor angiogenesis(TA) refers to the growth of new vessels toward and within a tumor. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, the microvessels were counted (per 200 / field) in the most active areas of neovas-cularization by two investigators. The microvessels within breast carcinoma were highlighted by in imunohistochemical staining for factor VIII-related antigen. Microvessel count(MVC) in node-positive carcinoma(59.66=35) was significantly higher than in node-negative carcinoma(44.76=17)(p=0.009). MVC was also statistically correlated with tumor size and stage, but not with histologic grading, DNA ploidy, or hormonal receptors(estro-gen and progesterone). MVC in invasive breast carcinoma may be one of many prognostic predictors of node-positive breast carcinoma. Assessment of tumor angiogenesis may therefore be valuable in selecting patients with early breast carcinoma for aggressive therapy.

Expression of ICAM-1 on Short-Term Cultured Human Keratinocytes: Modulation by IFN-gamma, UVB and retinoic acid.: Bang Hur, Duck Ha Kim, Man Ha Hur; Korean J Pathol. 1995;29(6):746-755.

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Abstract PDF: Intercellular adhesion molecule I(ICAM-1; CD 54), a 90 kD glycoprotein, counter-receptor for lymphocyte function-associated antigen-I(LFA-1) on T-cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. Induction of ICAM-1 on the keratinocytes(KCs) is an important regulator in initiation, maintenance, and resolution of cutaneous inflammation, which is modulated with cytokines produced by activated T-lymphocytes. This study was designed to further our understanding on modulation effects of ultraviolet B(UVB), gamma interferon(IFN-;v), and retinoic acid(all trans) upon expression of ICAM-1 on cultured human KCs, with emphasis on their correlation. Cell surface expression of ICAM-1 in cultured human KCs was analyzed with the use of indirect immunofluorescence and fluorescence activating cell sorting(FACS) by flow cytometry. The results of this study were as follows: 1) Expression of ICAM-1 was significantly induced with IFN-,-(20 U/ml)(p<0.005). 2) UVB irradiation of 30mJ/cm2 significantly suppressed ICAM-1 expression of KCs 24 hours after irradiation(p<0.05). However, at 72 hours after irradiation, ICAM-1 expression of KCs was considerably increased in comparison to that of initial phase (24 hours after irradiation). 3) High concentrations(10(-5)M) of retinoic acid reduced UVB-induced expression of ICAM-1 in late phase(72 hours after irradiation), although retinoic acid showed induction effect of ICAM- I expression of KCs. In summary, these results indicate that ICAM- I may contribute to the biphasic effect of UVB on delayed hypersensitivity in vivo. Also, retinoic acid, a vitamin A derivative, may have a cutaneous photoprotective effect through a regulation of UVB-induced ICAM-1 expression on the KCs.

Immunohistochemical and Ultrastructural Studies on the Histogenesis of Thyroid Undifferentiated Carcinoma.: Myoung Ja Jeong, Woo Sung Moon, Young Hye Lee, Myoung Jae Kang, Ho Yeul Choi, Sang Ho Kim, Dong Geun Lee; Korean J Pathol. 1995;29(6):756-765.

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Abstract PDF: Histologic, immunohistochemical and ultrastructural studies were performed on 6 cases of undifferentiated thyroid carcinoma to study the histogenesis of the undifferentiated thyroid carcinoma, to determine the most useful markers for diagnosing these tumors and to investigate the nature of osteoclast-like giant cells rarely observed in these tumors. For the immuno-histochemical study, a panel of antibodies to epithelial (cocktailed keratin, low molecular weight keratin, CEA), mesenchymal(vimentin, desmin, actin, FVIIIRAg) endocrine(calcitonin, chromogranin), lymphocytic(LCA), histiocytic(alpha-l-ACT, alpha-1-AT, lysozyme, CD68), and Schwann cell(S-100 protein) markers were used. The following results were obtained; 1) Well differentiated carcinoma was associated with 2 cases of spindle cell type and 1 case of giant cell type of undifferentiated thyroid carcinoma and a transitional zone between the well differentiated and undifferentiated lesions was observed. 2) All of the examined cases expressed keratin, and 3 tumors expressed CEA. 3) All the mesenchymal markers, LCA, S-100 protein, calcitonin, and chromogranin were not expressed. Vimentin was coexpressed with keratin in 4 cases. 4) Osteoclast-like giant cells were observed in 1 case of spindle cell type. They expressed CD68 but not keratin. 5) Ultrastructural study revealed the desmosomes between the tumor cells and non-neoplastic, follicular, thyroid epithelial cells. The above results indicate that undifferentiated thyroid carcinoma originates from follicular epithelial cell, keratin is the most useful marker for diagnosis of this tumor, and the osteoclast-like giant cells are histiocytic in nature and reactive, rather than neoplastic.

Immunohistochemical Study for p53 and hsc70 in Transitional Cell Carcinoma of the Urinary Bladder: Correlation with Histologic Grade, Clinical Stage and DNA Ploidy Pattern.: Hyuni Cho, Sung Jin Cho, Han Kyeom Kim, Yang Seok Chae; Korean J Pathol. 1995;29(6):766-775.

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Abstract PDF: Transitional cell carcinoma of the urinary bladder is the most common cancer of the genitourinary tract in Korea and its prognosis is determined by the histologic grade and clinical stage present at initial diagnosis. Recently, an extensive search for a more objective and reproducible method to evaluate the proliferation activity of cancer cells has been done. The p53 gene is located on the short arm of the chromosome 17 and acts as a cancer suppressor gene. Mutant p53 gene induces malignant transformation. Recent studies reveal that the level of mutant p53 protein is elevated in some human tumor and many diverse transformed cell lines. Heat shock proteins(HSPs) are present constitutively in normal cells, where they play an important role in normal cell metabolism. In mammalian cells, they are induced by a variety of physical and chemical stimuli. A protein that belongs to the hsp70 family, called hsc70, is only slightly heat inducible and is found at a higher level in growing cells than in the resting cells. The mutant p53 protein binds with hsc70 and the p53-hsc70 complex has functional significance in the transforming capacity of the mutant p53. We investigated the correlation between the p53 and hsc70 by immunohistochemical methods and with better defined prognostic indicators such as histologic grade, clinical stage, and DNA ploidy pattern in 42 transitional cell carcinomas of the urinary bladder. The results are summarized as follows. p53 expression rate was higher in the DNA aneuploid group than in the DNA diploid group(p=0.061), but there was no significant difference in the histologic grade(p=0.861) or clinical stage(p=0.154). The higher the hsc70 expression rate was, the poorer the tumor differentiation(p=0.000) and the deeper the invasion(p=0.001). The aneuploid group showed a higher hsc70 expression rate than the diploid group(p=0.017). 27 of 42(64.3%) carcinomas showed positivity of both p53 and hsc70. Though statistically insignificant, their correlation showed a relatively low correlation coefficient (P=0.059). In conclusion, we suspect that p53 and hsc70 are closely correlated to each other by comparing the results of this immunohistochemical study, and hsc70 will be a useful prognostic marker in transitional cell carcinomas of the urinary bladder after sufficient follow up studies are performed.

Infantile Myofibromatosis(Congenital Generalized Fibromatosis): Associated with multiple congenital malformations and basaloid follicular hamartomas in the skin.: Eun Sook Nam, Yoo Hun Kim, Han Kyeom Kim, Insun Kim, Je Geun Chi; Korean J Pathol. 1995;29(6):776-782.

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Abstract PDF: Infantile myofibromatosis with systemic involvement is a very rare disease and is characterized by numerous nodules composed of spindle cells of a myofibroblastic nature. There are often disseminated throughout the subcutis, muscle, skeleton and viscera. We report an autopsy case of infantile myofibromatosis in a stillborn female fetus of 32 weeks of gestation. The nodules, Imm to 2 cm, were found over the whole body and viscera. The involved viscera were the heart, tongue, esophagus, gastrointestinal tract, portal areas of the liver, spleen anc pancreas. There were also associated malformations, viz., frontal meningoencephalocele, flexion defer-mities, syndactyly, cleft palate, agenesis of corpus callosum, pachygyria, diaphragmatic hemia, renal hypoplasia, etc. Multiple basaloid follicular hamartomas of the skin were noted on the face and extremeties. There are no previous reports in the literature of infantile myofibromatosis in conjunction with the above skin lesion and congenital malformations.

Case Report

Leiomyosarcoma of the Esophagus: Report of two cases, one with associated squamous cell carcinoma.: Sug Kyoung Ko, Man Ha Huh; Korean J Pathol. 1995;29(6):783-791.

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Abstract PDF: Two new cases of leiomyosarcoma of the esophagus, one with an associated squamous cell carcinoma, are presented with review of literature. lmmunohistochemical study of MDM2 gene is performed upon these cases, and one case revealed overexpression of the MDM2 protein, whereas the other case showed negative result. And the pathological significance of MDM2 gene expression in esophageal leimyosarcoma is discussed, as, to our knowlege, no esophageal leiomyosarcoma with confirmed MDM2 gene amplification has been reported in the literature, to date. Gross character of these tumors was polypoid. Microscopically, the tumors consisted of interlacing fascicles of elongated spindle-shaped cells. Mitoses could be found without difficulty, with more than five per 10 high power fields. The tumor cells of the both cases showed imunohistochemical reactivity for vimentin and actin. Electron microscopically parallel arrays of myofilaments with interspersed dense bodies in spindle cell components were confirmed. The itera-literature regarding the association of leiomyosarcoma with epithelial malignancy in the gastrointestinal tract as well as esophagus is reviewed, and we found that this is a highly unusual occurrences(3 cases reported so far).

Original Article

Squamous Metaplasia of the Pleura.: Hyun Ju Kim, Jeong Hee Lee, Gyung Hyuck Ko; Korean J Pathol. 1995;29(6):792-793.

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Abstract PDF: We report a case of squamous metaplasia of the pleura observed in a 51 year old man. Squamous metaplasia of serosal surface, and in particular of the pleura, is uncommon. The pathogenesis of squamous metaplasia is obscure, but it may be associated with chronic irritation.

Case Reports

Sebaceous Trichofolliculoma: A case report.: Jeana Kim, Seong Beom Lee, Seok Jin Kang, Soo Il Chung, Sun Moo Kim; Korean J Pathol. 1995;29(6):794-796.

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Abstract PDF: Sebaceous trichofolliculoma is a variant of trichofolliculoma which occurs in the sebaceous areas rich in follicles and is a relatively rare skin tumor. This tumor is a clinically and histologically easy tumor to recognize that is well differentiated. We examined a case of a consists of a 21-year-old female who had a pedunculated nodule on her scalp. Microscopically, the tumor was large, had a centrally located cavity lined by squamous epithelium and radially arranged sebaceous follicles connected to the cavity. No cytological atypia or recurrence after excision was found.

Tubular Apocrine Adenoma: A case report.: Seong Beom Lee, Jeana Kim, Seok Jin Kang, Sun Moo Kim; Korean J Pathol. 1995;29(6):797-799.

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Abstract PDF: Tubular apocrine adenoma is a rare benign tumor occuring most often on the scalp. We examined a case of a 69-year-old female who had a well demarcated solid nodule on the scalp. Pathol Microscopically, the tumor was composed of lobules of tubular structures. The tumor lobules were surrounded by a stroma of dense fibrous connective tissue. The tubular structures were usually formed of two rows of epithelial cells. In some areas, the widely dilated tubular structures showed papillary projections into the cavities. Some epithelial cells showed liculoma on decapitation secretion into the cystic structure. Problems of differential diagnosis with other adnexal tumors are briefly discussed.

Well-Differentiated Thymic Carcinoma, Spindle Cell Type, Arising from Anterior Mediastinum: A case report.: Hun Kyung Lee, Yeong Jin Choi, Seok Jin Kang, Byung Kee Kim, Sun Moo Kim, Sang In Shim; Korean J Pathol. 1995;29(6):800-803.

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Abstract PDF: Well differentiated thymic carcinoma(WDTC) was recently separated from cortical thymoma. It is characterized by a predominance of epithelial cells with usually low mitotic rate, an epidermoid differentiation with slight to moderate cytologic atypia and lobular growth pattern. In recent reports, an uncommon spindle cell variant of WDTC, which is composed of spindle shaped epithelial cells, has been described. We investigated an unusual case of WDTC consisted of purely spindle shaped epithelial cells in a 66-year-old female. Radiologically, the well demarcated mass was located in the anterior mediastinum with focal invasion into the surrounding left upper lung. The tumor, 10 x 8 x 5 cm, was encapsulated with thin fibrous tissue and showed a pale yellow solid and lobulated cut surface. Microscopically, it consisted of solid sheets of purely spindle shaped epithelial cells with mild atypism, a low mitotic rate and focal epidennoid differentiation.

Interfollicular Hodgkin's Lymphoma: A case report.: Lee So Maeng, Kyung Mee Kim, You Mee Kang, Chang Seok Kang, Sang In Shim; Korean J Pathol. 1995;29(6):804-806.

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Abstract PDF: An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described using the name Interfollicular Hodgkin's Disease. It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's desease. The importance of interfollicular Hodgkin's disease rests on its misdiagnosis as a benign lesion. We report a case of interfollicular Hodgkin's disease in a 34-year-old female patient in the inguinal area. The lymph nodes showed reactive follicular hyperplasia. The focal interfollicular spaces were invaded by Hodgkin's disease. The Reed-Stemberg cells stained positively with CD15 and CD30 antibody in the immunohistochemical stain. An in situ hybridization study looking for EBV was negative in these R-S cells.

Primary Atypical Carcinoid Tumor of Liver: A case report.: Won Ae Lee, Hong Yong Kim, Ill Hyang Ko; Korean J Pathol. 1995;29(6):807-810.

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Abstract PDF: Primary hepatic carcinoid tumors are extremely rare although the liver is a frequent site of metastases from intestinal carcinoids. Recently we investigated a case of primary hepatic atypical carcinoid in a 47-year-old man who had infested with Clonorchis sinensis for 20 years. The resected right lobe of the liver was almost completely occupied by a huge tumor, measuring 20 x 19 x 12 cm. The cut surfaces of the mass were solid, soft and pale yellow, accompanied by several small satellite nodules, measuring up to 1.5 cm in diameter. Microscopically, the tumor consisted of polygonal to columnar cells with eosinophilic granular cytoplasm forming Lym-numerous small acini and large trabeculae. Their nuclei were round to polygonal with coarse stone chromatin, had obscure to small nucleoli and frequent mitoses. There were multiple necrotic foci of varing sizes. The surrounding dilated bile ducts contained several degenerating worms on in of Clonorchis sinensis. The tumor cells were argyrophil-positive but argentaffin-negative. Immunohistochemically, the tumor cells were positive for cytokeratin, chromogranin and somatostatin but were negative for CEA, AFP, insulin, glucagon, ACTH, growth hormone and volve-prolactin. Ultrastructually, the tumor cells contained variable-sized numerous electron dense of neurosecretory granules.

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