Journal of Pathology and Translational Medicine

Volume 31(11); November 1997

Original Articles

Cellular Distribution of TGF-beta1 Peptide in Dimethylnitrosamine Induced Fibrosis of Rat Liver.: Sook Nyo Lee, Do Youn Park, Sun Kyung Lee; Korean J Pathol. 1997;31(11):1157-1165.

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Abstract: Recently attention has been focused on the biology of transforming growth factor-beta1 (TGF-beta1). TGF-beta1, a potent regulator of cell proliferation, stimulates the proliferation of many cell types of mesenchymal origin and inhibits the growth of many epithelial cells. But its cellular distribution and temporal expression remain unknown. The aim of this study was to investigate immunohistochemically the cellular distribution and temporal expression of TGF-beta1 during rat hepatic fibrosis induced by dimethylnitrosamine (DMN). At an early stage of liver fibrosis, there was evidence of multiple centrilobular hemorrhagic necrosis with parenchymal lobular collapse, and at a late stage, there was septal fibrosis with micronodule formation of the parenchyme. TGF-beta1 peptide was first expressed in centrilobular clusters of macrophage which were surrounded by many TGF-beta1 negative fat-storing cells (FSCs). Along with the progression of fibrosis, the TGF-beta1 peptide was expressed in the alpha-smooth muscle actin positive FSCs and also in some peripherally located hepatocytes of micronodules. Serum IFN-gamma was detected in the serum 2 weeks after an initial administration of DMN had reached the peak level at the 4th week and then markedly decreased at the 5th week. We think that TGF-beta1 peptide is produced by macrophages influenced by soluble IFN-gamma, and is expressed in the -smooth muscle actin positive mesenchymal cells and regenerating hepatocytes, and that this cytokine may have an important role in the synthesis of the extracellular matrix and in the regulation of hepatocytic regeneration.

CD34 Antigen Expression in Gastrointestinal Stromal Tumors.: Sun Hee Sung, Min Sun Cho, Woon Sup Han; Korean J Pathol. 1997;31(11):1166-1171.

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Abstract: Gastrointestinal stromal tumor (GIST) is known as considerable controversal tumor about it's histogenesis, differentiation and biologic behavior. It is traditionally regarded as smooth muscle tumor. To evaluate and clarify the origin of tumor, we performed immunohistochemical study of 23 cases of GIST on CD34 antigen, alpha-smooth muscle actin, S-100 protein, and compared the result with 4 cases of typical leiomyoma of GI tract. The results were as follows. CD34 antigen expression was noted in 21 cases (91.3%) of GIST, while typical leiomyoma was all negative. There were no difference of CD34 expression according to the biologic behavior. However, it's staining pattern was significantly different (p<0.05). Focal or multifocal expression was dominant in benign GIST (58.3%), while diffuse expression was dominant in malignant GIST (80%). Actin was expressed in 5 cases of benign GIST (38.5%) and 1 of malignant GIST (16.7%) focally. All typical leiomyoma showed diffuse strong positivity on alpha-smooth muscle actin. S-100 protein was expressed in 2 cases of benign GIST (16.7%) only. The pattern of CD34 expression was focal in the actin or S-100 protein positive cases. In conclusion CD34 antigen is useful marker in the separation of GIST, from typical smooth muscle tumor. Also it suggest that most GISTs are histogenetically primitive mesenchymal cell origin. However, CD34 expression was unrelated with biologic behavior of GIST.

E-Cadherin Expression in Breast Carcinoma: Correlation with Tumor Grade and Hormone Receptor.: Haeng Ji Kang, Chan Pil Park, Chan Kum Park; Korean J Pathol. 1997;31(11):1172-1179.

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Abstract: E-cadherin (E-CD), a Ca2+ -dependent adhesion molecule, plays a major role in the maintenance of intercellular junctions in normal epithelial cells in most organs. Recently, a correlation has been observed between a loss of E-CD and increased invasiveness of neoplastic cells. In this study, E-CD expression in the breast carcinoma was investigated using monoclonal antibody, anti-E-CD by immunohistochemical method. Expression of E-CD were evaluated in 57 breast carcinomas and correlated with their tumor grade, lymph node involvement, and hormonal receptor status. Histological types included in this study were 54 invasive ductal carcinomas (IDCs) of otherwise not specified and 3 invasive lobular carcinomas. Cases of histologic grade I IDC were 6, grade II 30, and grade III 18. Of 54 IDCs 39 (72.2%) showed moderate to strong linear staining at the cell borders regardless of their histologic grade, status of lymph node metastasis, and status of hormone receptor. Staining intensity of E-CD was reduced in 54 cases (83%) of IDC when compared with that of normal or benign breast lesions (P<0.01). All seven cases of intraductal carcinoma, which were included in 54 IDCs showed one or two grade reduced expression of E-CD than that of infiltrative lesions. Three invasive lobular carcinomas showed strong (1 case), moderate (1 case), and negative reactivity (1 case). The data indicated that loss of E-CD expression is a crucial event in the development of breast carcinoma.

Expression of Apoptosis, bcl-2, and PCNA in Uterine Cervical Intraepithelial Neoplasia and Invasive Carcinoma.: Myoung Ja Chung, Kyu Yun Jang, Myoung Jae Kang, Dong Geen Lee, Byung Chan Oh; Korean J Pathol. 1997;31(11):1180-1189.

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Abstract: This study was undertaken to know the extent of apoptosis, expression of bcl-2 and proliferating cell nuclear antigen (PCNA) in uterine cervical intraepithelial neoplasia (CIN; 15 cases) and invasive carcinoma (27 cases) and to evaluate them as a prognostic marker. Apoptosis was analysed by using the in situ apoptosis detection kit and bcl-2 and PCNA were detected by the immunohistochemical method. The results were as follows: Apoptotic indices (AI) in the invasive carcinoma (mean: 4.3) were 10-times higher than that in the CIN (mean: 0.43). Bcl-2 was expressed 60% of the cases in the dysplastic cells of the CIN II and CIN III, 33.3% of cases in the invasive carcinoma and not expressed in the CIN I except basal cells. The expression of the PCNA was increased by the grades of CIN and was strong in invasive carcinoma. The mean survival time of the patient with invasive carcinoma was significantly decreased in the higher AI index (above 4.3) than in the lower AI index (below 4.3). There was no significant correlation between the extent of apoptosis and the expression of bcl-2. According to the above results, AI are able to be used as an independent prognostic marker in the invasive cervical carcinoma, and bcl-2 and PCNA have an important role in the tumorigenesis of uterine cervical carcinoma.

Structural-Functional Relationships in Renal Amyloidosis.: Myeong Cherl Kook, Hyun Soon Lee; Korean J Pathol. 1997;31(11):1190-1199.

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Abstract: The pathogenetic mechanism of renal dysfunction in renal amyloidosis is poorly understood. To evaluate the morphologic parameters which are correlated with renal function in this disorder, we have examined renal biopsies from 14 patients with renal amyloidosis by morphometry. Of the 14 patients, 8 were male and 6 were female. They were between 41 and 70 years of age. The serum concentration of albumin and creatinine were 2.1+/-0.7 mg/dl and 1.1+/-0.5 mg/dl, respectively. The 24-hour excretion of urinary protein was 7.9+/-5.2 g. Creatinine clearance was 62+/-23 ml/min/1.73m2. The mean glomerular volume (MGV) was (2.2+/-1.3) 10(6) micrometer3. The surface density of peripheral glomerular basement membrane [Sv (PGBM/glom)] was 0.049+/-0.027 (micrometer3/micrometer3). Volume density of mesangium [Vv (mes/glom)] was 0.31+/-0.14 (micrometer3/micrometer3) and volume density of glomerular amyloid deposition [Vv (amyl/glom)] was 0.21+/-0.14 (micrometer3/micrometer3). The volume density of cortical interstitium [Vv (int/cortex)] was 0.14+/-0.09 (micrometer3/micrometer3). The serum creatinine concentration was significantly correlated with Vv (int/cortex) (r=+0.66, p<0.05). MGV was correlated with Vv (mes/glom) (r=+0.75, p<0.01) and Vv (amyl/glom) (r= +0.68, p<0.05) but showed negative correlation with Sv (PGBM/glom) (r=-0.79, p<0.01). Sv (PGBM/glom) showed negative correlation with Vv (mes/glom) (r=-0.77, p<0.01) and with Vv (amyl/glom) (r=-0.87, p<0.01). Positive correlation was observed between Vv (mes/glom) and Vv (amyl/glom) (r=+0.95, p<0.01). These results suggest that the decreased renal function in patients with amyloidosis is related to interstitial fibrosis rather than glomerular lesions. In addition, glomerular hypertrophy in these patients is related to amyloid deposition in the mesangium and peripheral glomerular basement membrane.

Immunohistochemical and Ultrastructural Observation on Small Round Cell Tumors.: Chae Hong Suh, Jeong Yeol Yang, Sung Chul Lim, Yong Lim Kim; Korean J Pathol. 1997;31(11):1200-1213.

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Abstract: Small round cell tumors such as neuroblastoma, rhabdomyosarcoma, Ewing's tumor, malignant lymphoma and small cell carcinoma are often confused clinically and histologically. To clarify the similarites and differences and to get more information on the histogenesis among the small round cell tumors, we examined histological, immunohistochemical and ultrastructural features of ten cases of neuroblastomas, twenty Ewing's tumors, ten embryonal rhabdomyosarcomas and twelve small cell carcinomas in children and young adults. Antibodies against desmin, vimentin, cytokeratin, neuron-specific enolase, synaptophysin, neurofilament, S-100 protein, chromogranin and HBA 71 were used in biotin streptavidin procedures. The results of the immunohistochemical and electron microscopical examinations yielded virtually identical findings in each group as followings. 1) Among the twenty cases of Ewing's tumors, eighteen cases were positive in staining for HBA-71. The staining for HBA-71 was negative in neuroblastoma, embryonal rhabdomyosarcoma and small cell carcinoma. 2) Neuroblastomas had marked interdigitating cytoplasmic processes containing many microtubules and dense-core secretory granules, however, they were sparse and rare in Ewing's tumor. 3) Embryonal rhabdomyosarcoma showed actin-myosin bundles. According to differentiation, well differentiated rhabdomyosarcoma exhibited Z-band materials and external lamina. 4) Neuroblastoma showed ultrastructural evidence of a neuronal differentiation, but neuronal differentration is a sparse and rare in Ewing's tumor. This ultrastructural feature strengthens the hypothesis that Ewing's tumor is derived not only from an undifferentiated neuroectodermal stem cell but from primitive cell of neuroectodermal origin.

Cytologic and Histologic Correlation for Quality Assurance in Aspiration Cytology.: Ho Jung Lee, Young Mee Cho, So Young Park, Joo ryung Huh, On Ja Kim, Gyung Yub Gong; Korean J Pathol. 1997;31(11):1214-1221.

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Abstract: For quality assurance purposes, the authors correlated aspiration cytology and subsequent tissue findings and examined the reasons for discrepancies. In three months from Jan. to Mar. 1996, 1,383 aspirations were performed, of which 285 (20.6%) had subsequent tissue diagnoses within two months. The aspiration sites were thyroid (483), lymph node (LN) (290), breast (250), soft tissue (154), liver (89), lung (49), salivary gland (26), pancreas (22), gallbladder (3), bone (3), joint (2), adrenal gland (2), scrotum (2), mediastinum (2), omentum (2), oral cavity (1), chest wall (1), and intraabdominal (1) and pelvic cavities (1). A total of 68 discrepancies were identified, and biopsies and smears from these cases were reviewed monthly. In 27 cases (40%), the discrepancy was attributed to sampling error. In five cases (9%), aspiration gave superior results with better sampling and preservation than biopsy. Thirty six cases (53% of discrepant cases) were errors in cytologic diagnosis. We categorized these discrepancies into "A", "B", and "C" ("A": minor disagreement with no affect on patient care, "B": minimal affect on patient care, "C": major affect on patient care), which were 9 (13%), 14 (21%) and 13 (19%) cases, respectively. In thirteen cases of category "C", there were eleven false negative and two false positive diagnoses. Eleven false negative cases included thyroid (3), lymph node (2), breast (2), bone (1), salivary gland (1), lung (1), and liver (1). Three cases of thyroid were papillary carcinomas diagnosed as nodular hyperplasia (1), occasional pleomorphic cells (1), and cystic change (1). Two breast cases of invasive ductal carcinomas were diagnosed as ductal hyperplasia. A malignant lymphoma was diagnosed as reactive hyperplasia and a metastatic carcinoma of LN was diagnosed as tuberculosis. Other cases were malignant tumors of bone, salivary gland, lung, and liver those were misinterpreted as benign lesion or normal. Of two false positive cases, one was nodular hyperplasia of thyroid diagnosed as papillary carcinoma and the other was normal islet cell of pancreas diagnosed as islet cell tumor. A continuous monitoring of laboratory performance is an essential component of the quality control and assurance, and the review of discrepant cases provides useful information for improvement of diagnosis.

Case Reports

A Sialoblastoma Associated with a Hepatoblastoma: An autopsy case report.: Sun Lee, Youn Wha Kim, Jae Hoon Park, Yong Koo Park, Ju hie Lee, Moon Ho Yang; Korean J Pathol. 1997;31(11):1222-1226.

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Abstract: Sialoblastoma is defined as a rare, congenital or perinatal, aggressive and potentially low-grade malignant, basaloid gland neoplasm that occurs in the major salivary glands. We report a case of a congenital sialoblastoma in the left parotid gland, associated with a hepatoblastoma in a female infant. At birth, a huge mass in the left neck and hepatomegaly were noted. Grossly, the neck mass was well-circumscribed, lobulated and gray tan. Microscopically, the tumor was composed of basaloid aggregates of primitive uniform cells with focal ductal differentiation. The liver showed a well-circumscribed gray tan tumor with extensive hemorrhage and cystic change. Microscopically, the liver revealed characteristic findings of hepatoblastoma. To the best of our knowledge, this is the first case of coexistence of a congenital sialoblastoma and a hepatoblastoma, reported in the literature.

Congenital Sialoblastoma: A case report and review.: Jong In Yook, Hee Jeong Ahn, Jin Kim; Korean J Pathol. 1997;31(11):1227-1232.

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Abstract: A congenital salivary gland tumor, sialoblastoma, is extremely rare. A sialoblastoma of the parotid gland, occurring in a 28-week old fetus, is described. The histologic, immunohistochemical, and ultrastructural features of this tumor were studied. The tumor was characterized by solid nests or sheets of tumor cells intermingled with ductal structures lined by a columnar cells. Some of the tumor cells showed squamous differentiation. Immunohistochemically, these epidermoid cells reacted positively with anti-cytokeratin. But anti-S-100, anti- vimentin, anti-smooth muscle actin, anti-GFAP positive cells were not found. The ultrastructure was characterized by primitive epithelial cells. Although various names have been proposed, we favored the term "sialoblastoma". The histogenesis of this tumor is also discussed.

Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Report of an autopsy case.: Tae Yub Kim, Young Min Kim, Jae Gul Chung, Gyung Yub Gong, Su Kil Park, In Chul Lee, Joo Ryung Huh; Korean J Pathol. 1997;31(11):1233-1236.

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Abstract: A 35-year-old man was admitted with a 20 day history of generalized edema and muscular weakness of the lower extremities. He was alert with a pale puffy face and an ejection murmur was heard at the cardiac apex. The electrocardiogram disclosed low voltage, first degree atrioventricular block, and a right bundle branch block. During the hospitalization an intractable diastolic hypotension developed, which measured 0 mmHg at the lowest point. At that time the echocardiogram revealed a dilated, akinetic right ventricle. Eventually a multiorgan failure developed and an autopsy following his death presented a fibrofatty replacement of the right ventricular myocardium. This might be a case of an arrhythmogenic right ventricular dysplasia/cardiomyopathy, which is usually characterized clinically by a ventricular tachycardia and may cause a sudden death in young adults.

Enteric Cyst in the Tongue.: Jeong Yun Shim, Ho Guen Kim; Korean J Pathol. 1997;31(11):1237-1239.

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Abstract: A case of enteric cyst in the anterior two-thirds of the tongue is reported. The patient, a 42 day-old female infant, presented with a protruding tongue mass since birth. Under the impression of ectopic thyroid gland or leiomyoma, complete resection was performed. The mass proved to be an enteric cyst, lined by small intestinal mucosa with an underlying coat of smooth muscle. Enteric cysts arising in the tongue is rare and only 8 such cases have been reported in the literature.

Multilocular Cystic Renal Cell Carcinoma.: Myoung Jin Ju, Kee Tac Jang, Je Geun Chi; Korean J Pathol. 1997;31(11):1240-1243.

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Abstract: Multilocular cystic renal cell carcinoma is a distinct subtype of renal cell carcinoma with its pathological characteristics and good prognosis. Multilocular renal cysts and renal cell carcinoma with cystic change are important differential diagnoses. We report a case of multilocular cystic renal cell carcinoma in a 37-year-old woman who came to the hospital because of the right renal mass. The removed right kidney showed a 6x4 cm well defined cystic mass in the lower pole. On cut section there were multiple cavities in the mass, filled with serosanguineous fluid and focal yellowish solid area. Microscopically, these cysts were lined by a single layer of flat or cuboidal cells consisted of clear cytoplasm with small central nuclei. In some portions of the tumor, the clear neoplastic cells formed sheets within the septa or walls of the cysts.

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