Journal of Pathology and Translational Medicine

Volume 29(2); April 1995

Original Articles

Flow Cytometric DNA Analysis in Thyroid Neoplasms: With Emphasis on the Correlation between Ploidy Level and Pathologic Features.: Young Tae Kim, Jin Man Kim, Kwang Sun Suh, Jin Sun Bae; Korean J Pathol. 1995;29(2):127-135.

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Abstract PDF: Nuclear DNA content in 31 cases of thyroid neoplasm was determined by flow cytometry with the use of paraffin-embedded archival tissue. DNA aneuploidy was found in 6 cases (19.4%) of the 31 thyroid neoplasms; such as 2 of 8 (DI=1.16, 1.56) follicular adenomas, 1 of 6 (DI=1.10) follicular carcinomas, 1 of 15 (DI=1.18) papillary carcinomas and 2 of 2 (DI=1.76, 2.07) medullary carcinomas. The remaining tumors were diploid. No significant difference between follicular adenomas and carcinomas was detected with respect to the S phase fraction(SPF). In the papillary carcinoma group the SPF was higher than in the follicular neoplasm group, but it was statistically insignificant. Regional lymph node metastasis was present in 8 of 15( 53.3%) papillary carcinomas but absent in all of the 14 follicular neoplasms. In the medullary carcinoma group one case showed regional node metastasis at the time of resection and the other developed metastasis 11 months after surgical removal of the primary lesion. In this study tumors predominantly composed of Hurthle cells were found to have a significantly higher D.I. than those with few or no Hurthle cells. No significant difference was found between tumors with metastasis and those without metastasis.

A Study of the Correlation between Expression of c-erbB-2 Oncoprotein and Various Clinicopathological Prognostic Factors in Breast Carcinoma.: Jong Hee Nam, Kyung Soo Kim, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 1995;29(2):136-144.

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Abstract PDF: Immunohistochemical study for c-erbB-2 oncoprotein was performed on paraffin sections of 76 primary breast carcinomas to determine the relationship between expression of c-erbB-2 and various clinicopathological prognostic indicators, including the expression of epidermal growth factor receptor (EGFR). Positive reaction for c-erbB-2 oncoprotein revealed an intense red granular staining predominantly located at the tumor cell membrane, with some cells exhibiting a weak cytoplasmic staining as well. The epithelial cells of the normal lobule and duct showed a negative reaction. Positive reaction for EGFR revealed a granular staining in the cytoplasm and the cell membrane of the tumor cells. Some tumors showed a positive EGFR staining in the epithelial cells of normal duct and lobule. Twenty six of 76 cases (34.2%) of primary breast carcinomas revealed a positive reaction for c-erbB-2 oncoprotein, and 28 cases (36.8%) were positive for EGFR. Expression of c-erbB-2 oncoprotein and EGFR was evident in 37.7% and 40.6% of 69 classic invasive ductal carcinomas, respectively. None of the other histological types showed a positive reaction. Expression of c-erbB-2 oncoprotein was strongly associated with tumor size(p=0.0015), histologic grade(.p=0.0175), vascular invasion(p=0.0043), and lymph node metastasis(p=0.0024), but not with age at diagnosis(p=0.1836). No significant association was found between expression of c-erbB-2 oncoprotein and EGFR. Co-expression of c-erbB-2 oncoprotein and EGFR was also strongly associated with tumor size (p=0.0029). These results suggest that c-erbB-2 oncoprotein is biologically distinct from EGFR, and may be used as a prognostic indicator of breast carcinoma due to its strong association with various clinicopathological prognostic factors.

Infantile Hemangioendothelioma of the Liver: A histological and immunohistochemicalstudy of 4 cases.: Mee Yon Cho, Sun Hee Sung, Soon Hee Jung, Chanil Park; Korean J Pathol. 1995;29(2):145-151.

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Abstract PDF: A pathological study was performed on four cases of infantile hemangioendothelioma of the liver. All the patients were between the age of 1 -5 months and the tumors were typical hemangio-endotheliomas, type 1. The tumors were composed basically of two components; the endothelial cell proliferation and the myxoid matrix. The endothelial cells were cytologically innocuous and formed vascular channels of varying sizes and shapes from capillary to sinusoidal and cavernous vessels. Fibrosis of the matrix, albeit not a major component of the tumor, was found particularly near the center. Immunohistochemically, CD31 was expressed strongly in almost all endothelial cells, in contrast to the stain for von Willebrand factor which was only focally and weakly positive. Alpha-fetoprotein was expressed in hepatocytes within the tumor or in hepatocytes around the tumor. Intratumoral bile duct structures were located mainly at peripheral portion. The results indicated that the type I infantile hemangioendothelioma is a tumor of endothelial cells and myxoid stroma, and that the endothelial cells undergo gradual maturation to form sinusoidal and cavernous vessels in accordance with gradual fibrosis of the myxoid stroma.

A Study of the Correlation between Cellular Proliferating Activities and Prognosis in Gastrointestinal Stromal Tumors .: Hee Jin Chang, Duck Hwan Kim, Sung Sook Pang, Jin Hee Sohn, Jung Il Suh, In Sun Kim, Jong Sang Choi; Korean J Pathol. 1995;29(2):152-169.

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Abstract PDF: Gastrointestinal stromal tumors are notorious for their unpredictable clinical behavior. To assess the cellular proliferating activities, four different methods were used: mitotic count, nucleolar organizer region(AgNOR) staining, immunostaining of proliferating cell nuclear antigen (PCNA) and DNA ploidy were used on 39 cases of gastrointestinal stromal tumors. Additionally, we analysed cellularity, cellular atypism and necrosis. Among 39 cases of gastrointestinal stromal tumors, 11 cases were diagnosed as benign lesions according to clinicopathologic findings. Malignant lesions were arbitrarily classified into low grade(n=ll) and high grade(n=17) on the basis of absence or presence of recurrence, metastasis or tumor-related death during the follow-up period. Numbers of mitosis, AgNORs, PCNA index and DNA ploidy were correlated with grades of tumor and prognosis. Among them, AgNORs counting appeared to be the most useful in predicting prognosis. Numbers of mitosis, PCNA index and DNA ploidy showed varying degrees of overlap among the 3 groups. Among the histological parameters, cellular atypia showed some relationship with the prognosis that others did not reveal.

Prognostic Implications of DNA Ploidy and S-phase Fraction Comparing with Other Prognostic Factors in Advanced Coloretal Adenocarcinomas .: Young Il Yang, Jong Eun Joo; Korean J Pathol. 1995;29(2):170-180.

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Abstract PDF: Dukes' stage of colorectal carcinoma has proven to be the most reliable and conventional prognostic indicator, followed by histological grade, lymph node metastases, tumor size, vascular and neural invasion. Flow cytometric analysis of DNA ploidy and S-phase fraciion (SPF) was examined to elucidate the correlations between sex, age, preoperative serum carcinoembryonic antigen (CEA) value, Dukes' stage, tumor site, size, gross features, histologic grade, and survival rate in 117 paraffin-embedded tissues of 68 cases of colorectal adenocarcinoma in Dukes' stage and 39 cases of colorectal adenoma and 10 cases of normal colonic mucosa. DNA aneuploidy was detected in 30 cases(44%) in adenocarcinomas and 6 cases (15%) in adenomas. Although the DNA ploidy and SPF did not show any correlation with sex, age, preoperative serum CEA level, Dukes' stage, tumor size, site and gross features, the incidence of DNA aneuploidy in the moderately differentiated adenocarcinomas was significantly higher than that of the well differentiated adenocarcinomas (p=0.0127) An apparent correlation was found between survival rate and DNA ploidy, Dukes' stage, histologic grade and preoperative serum CEA value. Dukes' stage was the most reliable prognostic indicator (p=0.0106), followed by histologic grade (p=0.0230), DNA aneuploidy (p=0.0251) and preoperative serum CEA level. (p=0.0369) In the patients with Dukes' stage C, DNA aneuploidy was more important than histologic grade as a prognostic indicator (p=0.0202). Although high SPF, greater than 21% in adenocarcinoma, was associated with the lower 5-year survival rate (12.0%), it was not statistically significant. These results suggest that DNA aneuploidy is regarded as biologic aggressiveness and considered as independent and/or dependent prognostic indicator along with Dukes' stage. However, prognostic utility of the SPF was not significant.

Diffuse Neurofibromas: Clinicopathologic Analysis of 11 cases.: So Young Park, Hye Kyung Lee, Se Min Baek; Korean J Pathol. 1995;29(2):181-188.

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Abstract PDF: We reviewed surgical specimens from 11 patients with diffuse neurofibroma to define the specific clinicopathologic characteristics. Ten cases were cutaneous neurofibromas and one case was an uncommon gastrointestinal neurofibroma involving the rectum. The most frequent sites of involvement were the head and neck, especially the eyelids and the periorbital areas. They usually presented as a plaque-like elevation of the skin. They primarily occured in children and young adults and positive family histories of von Recklinghausen's neurofibromatosis were obtained in 45.4%. Pathologically, the involved skin & rectum were diffusely thickened by an infiltrative growing mass, showing proliferation of short fusiform cells in the uniform matrix of fine fibrillary collagen. The characteristic prominence of Wagner-Meissner bodies (45.4%) suggests they could be associated with pathogenesis of diffuse neurofibroma. On the basis of these findings, we could confirm diffuse neurofibroma to be a distinct form of neurofibroma.

Immunohistochemical Evaluation of HMB-45 and S-100 Protein in Melanocytic Tumors.: Chang Soo Park, Hwan Kim, Hyang Mi Ko, Kyung Soo Kim, Ji Shin Lee; Korean J Pathol. 1995;29(2):189-196.

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Abstract PDF: Immunohistochemical staining on paraffin sections for S-100 protein improved diagnostic accuracy for melanocytic tumor. But specificity of S-100 protein in the diagnosis of melanocytic tumor is very low, because S-100 protein was also expressed in neurogenic tumor and salivary gland tumor. To investigate a specific tumor marker for the malignant melanoma, immunohistochemical staining for HMB-45 and S-100 protein was performed on the paraffin sections of 25 cases of malignant melanoma and 46 cases of nevi. Positive reaction for HMB-45 and S-100 protein was diffusely identified in the cytoplasm of tumor cells. Positive ratio for HMB-45 was 100% in malignant melanoma, 92% in junctional component of compound nevus and 0% in intradermal nevus. Positive ratio for S-100 protein was 92% in malignant melanoma, 100% in compound nevus and 100% in intradermal nevus. The sensitivity and specificity for HMB-45 in malignant melanoma were 100%, but those for S-100 protein were 92% in sensitivity and 86.7% in specificity. These results indicate that HMB-45 has a high sensitivity and specificity for malignant melanoma cells and it can be quite useful for the histopathological diagnosis of malignant melanoma.

Morphological Changes of Hepatic Microcirculation in N-diethylnitrosamine Induced Cirrhotic Rat Liver.: Sang Han Lee, Ji Hwa Kim, Ik Su Kim, Jong Min Chae; Korean J Pathol. 1995;29(2):197-204.

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Abstract PDF: Morphological changes of hepatic microcirculation, especially in the peribiliary plexus, in cirrhotic livers of rats induced by repeated intraperitoneal injections of N-diethyinitrosamine (DEN) (100mg/kg/week) were studied by scanning electron microscopy. Control rats were treated with saline. The livers were perfused with saline and injected with methyl-methacrylated resin (Mercox CL-2B) through the thoracic aorta. Diffuse nodular changes mimicking human cirrhosis were seen in the livers six weeks after injections of DEN. The cirrhotic livers showed an increase of vascular channels composed mainly of venous branches around the regenerating nodules and increased arterioloportal anastonloses. Peribiliary plexi of the cirrhotic livers had more vessels than those of the controls. Many dilated veins and ramificating portal vein branches were also Present. Direct connections between peribiliary plexi and sinusoids or between peribiliary plexi and portal veins were increased in the cirrhotic liver. These results suggest that the peribiliary plexi in experimentally induced cirrhotic liver might play a role in a collateral circulation under a state of portal hypertension.

Immunohistochemical Study of Heat Shock Protein(HSP) and Estrogen Receptor(ER) in the Normal Endometrium and in Adenocarcinoma of the Endometrium.: Hyuni Cho, Aeree Kim, Yung Suk Lee, Han Kyeom Kim, Insun Kim; Korean J Pathol. 1995;29(2):205-211.

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Abstract PDF: Heat shock protein(HSP), first found in the MCF-7 human breast tumor cell line is one of the estrogen-regulated proteins and its synthesis is stimulated by estradiol. In this study, immunohistochemical staining was done for estrogen receptor(ER) and HSP on formalin-fixed, paraffin-embedded tissue sections in twelve normal cyclic and twenty carcinomatous endometria. 1) During the proliferative and early secretary phases, the nuclei of surface and glandular epithelial cells and stromal cells had moderate to strong staining for ER, whereas during the mid and late secretary phases, the glandular epithelial and stromal cells had weak staining for ER. The surface epithelial cells had positive staining of variable intensity. 2) From the early proliferative to mid secretary phases, the glandular and surface epithelial cells showed a positive reaction of variable intensity for HSP. In the late secretary phase, the glandular and surface epithelial cells showed a weak positive or a negative reaction for HSP. During the menstrual cycle, the stromal cells remained negative for HSP. 3) In adenocarcinomas of the endometrium, 8 of 11 (72.7%) well differentiated carcinomas were positive for both ER and HSP, while only 3 of 9(33.3%) moderately and poorly differentiated carcinomas were positive for ER and HSP. In conclusion, ER and estrogen-regulated heat shock protein(HSP) were closely related in normal and carcinomatous endometria and the reactivity was decreased according to poor differentiation.

Expression of Interleukin-6 in Induced Viral Myocarditis in Mice.: Soo Yeon Cho, Hye Kyung Jin, Min Sun Cho, Sung Sook Kim, Woon Sup Han, Dong Sun Han, Hak Chung Lee; Korean J Pathol. 1995;29(2):212-220.

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Abstract PDF: Viral myocarditis is considered an important cause of dilated cardiomyopathy. At preseent, two mechanisms are known to be involved in the pathogenesis of viral myocarditis and subse-quent cardiomyopathy: viral direct toxicity and immune mediated toxicity. Some authors have reported that IL-6 influences the immunologic mechanism and the virus-induced tissue damage in myocarditis. We injected encephalomyocarditis(EMC) virus to induce viral myocarditis in ICR mice. In order to study the lymphocyte subset and IL-6 expression to clarify the immune mechanism and to demonstrate the role of IL-6 in viral induced myocardial damage. The following results were obtained: 1) In virus inoculated mice, inflammation was severest at 10 days, and some serious complications developed, indicating a possible transition to dilated cardiomyopathy. 2) On analysis of the lymphocyte subset, CD4 cells were most prevalent at 5 days and CD8 cells were most prevalent at 10 and 20 days. 3) IL-6 was significantly increased and expression of IL-6 was constant, but its intensity was strongest at 5 days. In conclusion, IL-6, produced by inflammatory cells, fibroblasts, and endothelial cells, might play an important role in myocardial damage in experimentally induced EMC viral myocarditis by its direct cytotoxicity or cytokine mediated activation of cytotoxic cells.

Yellowish Degeneration of Uterine Leiomyomas: Light Microscopic and Ultrastructural Observations.: So Dug Lim, Joo Ryung Huh, Yong Il Kim; Korean J Pathol. 1995;29(2):221-227.

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Abstract PDF: We reviewed five cases of Uterine leiomyomas, each with a conspicuously, yellow cut surface, among 198 consecutive cases of surgically removed uterine leiomyomas. Their gross findings were not significantly different from ordinary leiomyomas except for their pale to bright Yellowish cut surface. Microscopically, multiple small clusters of clear cells were widely scattered in otherwise hypercellular leiomyornas in 4 of the 5 cases. Of those, one case gave a positive reaction of Oil-Red O stain. Ultrastructurally, clear cells corresponded to the degenerating smooth muscle cells with intracytoplasmic lipid vacuoles. The rest of cells showed myofibers undergoing varying degrees of degeneration. Focal accumulation of foamy histiocytes was associated with carneous degeneration in one case. We conclude that the yellowish leiomyoma of the uterus seems, in part, to reflect accumulation of a lipid substance in degenerating hypercellular leiornyoma, or possibly collections of xanthoma cells in secondary degeneration.

Case Reports

Primary Carcinoid Tumor of the Testis: A case report.: Yikyeong Chun, Yeon Lim Suh; Korean J Pathol. 1995;29(2):228-231.

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Abstract PDF: Primary carcinoid tumors of the testis are exceedingly rare. They may originate as a pure form or as part of a testicular teratoma. To diagnose a testicular tumor as primary carcinoid, the possibility of metastasig must be carefully excluded. To our knowlege, none has been reported in Korean literature. We present a case of primary testicular carcinoid in a 36-year-old man. He had a painless, palpable mass on the right scrotum for 4 years. He underwent a radical orchiectomy. He is free of disease during 20 months postoperatively. Histologically and ultrastructurally this tumor showed a typical feature of carcinoid tumor of midgut derivation. A flow cytometric DNA analysis of this mass contained an aneuploid cell population.

Atypical Carcinoid of the Larynx: A report of two cases.: Yong Hee Lee, Young Nyun Park, Dong Hwan Shin, Yoo Bok Lee; Korean J Pathol. 1995;29(2):232-237.

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Abstract PDF: Atypical laryngeal carcinoid is a rare tumor with a poor prognosis, mostly occurring in the supraglottic larynx. It is a subtype of neuroendocrine carcinoma which should be separated from typical carcinoid and small cell carcinoma. The histogenesis and standardized classification of laryngeal neuroendocrine carcinoma have not been clearly defined. In this report, we present two cases of atypical laryngeal carcinoid, one occurring in a 67 year old male and the other in a 54 year old female. Indirect laryngoscopy revealed a polypoid supraglottic mass, approximately 3 cm in diameter. Microscopically, each case showed a moderate degree of pleomorphism, tumor necrosis and frequent mitoses. The immunohistochemistry revealed a strong positive reaction for chromogranin, neuron specific enolase and cytokeratin. Each patient had distant metastasis, noted within 4 months after resection (liver and stomach), and died postoperatively at 5 and 20 months, respectively. A brief review of the literature concerning the biological behavior, histogenesis and pathology of atypical laryngeal carcinoid was performed.

Fetal Death Secondary to Constriction and Torsion of Umbilical Cord: An autopsy case.: Yeon Mee Kim, Je G Chi; Korean J Pathol. 1995;29(2):238-240.

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Abstract PDF: Localized constriction and torsion of the umbilical cord are rare cord abnormalities. The seg- mental absence of Whartion's jelly in the involved area of the cord is believed to be an etiologic factor of the constriction and subsequent torsion. In the past, constriction and torsion were thought to occur after the death of the fetus as a result of maceration. However, recently it has been suggested that the torsion of the constricted area might cause fetal death. We report an autopsy case of a localized constriction and torsion of the umbilical cord in a stillborn baby. The baby was delivered to a 27-year-old primiparous woman after 28 weeks gestation. The fetus was of 24 gestational weeks in size and weight. And the placenta weight was 259 gm. A grossly macerated fetus showed a cystic hygroma in the posterior neck. There were two areas of constriction in the umbilical cord, one at the squamoamniotic junction and the other, 15 cm from the fetal end. Torsions were noted in both constricted areas, more severe than in the mid portion of the cord. Microscopically, the Whartion's jelly was deficient and partly replaced by fibrosis in the constricted areas. It is believed that these two areas of constrictions and torsion are causally related to the intrauterine fetal death in this case.

Biliary Cystadeoma of the Liver: Report of a congenital case.: Jai Hyang Go, Young Nyun Park, Woo Hee Jung, Chanil Park; Korean J Pathol. 1995;29(2):241-243.

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Abstract PDF: Biliary cystadenoma of the liver is a rare multilocular cystic neoplasm of biliary origin. it occurs most often in middle aged women and rarely in children. Histogenesis of this tumor is uncertain. It may be developmental in origin arising from aberrant hamartomatous bile ducts or ectopic rests of embryonic biliary cystadenoma of the liver discovered at 8 month of intrauterine fetal life. This case supports its congenital theory.

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