Journal of Pathology and Translational Medicine

Brief Case Report

A Case of Epithelioid Blue Nevus: Chung Hun Lee, Hye Sook Min, Eon Sub Park, Kye Yong Song; Korean J Pathol. 2014;48(6):434-437. Published online December 31, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.6.434

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A Curious Case of a Pigmented Lesion
Dilshad Sachedina, Marisa Taylor
Indian Journal of Dermatology.2024; 69(1): 104. CrossRef
Recurrence of a Cellular Blue Nevus with Satellitosis—A Diagnostic Pitfall with Clinical Consequences
Hermann Kneitz, Christian Rose, Valerie Glutsch, Matthias Goebeler
Dermatopathology.2022; 9(4): 361. CrossRef
Epithelioid Blue Nevus
Kai-Lv Sun, Jian-Min Chang
International Journal of Dermatology and Venereology.2020; 3(3): 186. CrossRef

Original Article

Expression of DNA Topoisomerase II-alpha as a Proliferating Marker in Urothelial Carcinoma of Urinary Bladder based on World Health Organization/International Society of Urological Pathology Consensus Classification: A Correlation with Expression of Ki-67 and Apoptosis: Tae Jin Lee, Dong Ki Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(5):305-313.

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Abstract PDF: BACKGROUND
DNA topoisomerase II-alpha is linked with active cell proliferation in mammalian cells. The aim of this study was to examine the relationship between the expression of DNA topoisomerase II-alpha as a proliferating marker, and the expression of Ki-67 and apoptosis in urothelial carcinoma of urinary bladder based on World Health Organization/International Society of Urological Pathology (WHO/ISUP) consensus classification.
METHODS
73 urothelial carcinomas of the urinary bladder after transurethral resection and 25 carcinomas after radical cystectomy were investigated for histologic grading based on WHO and WHO/ISUP consensus classification. Formalin fixed, paraffin embedded tissue of 98 specimens from 73 patients were immunohistochemically stained for DNA topoisomerase II-alpha and Ki-67, and in situ TdT-mediated dUTP-biotin nick end labeling method for evaluation of apoptotic cells was performed. For each case, a DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were determined.
RESULTS
The histologic grades of 73 cases based on the WHO grading system were 21.9% (16 cases) in grade 1, 65.8% (48 cases) in grade 2, and 12.3% (9 cases). 5.5% (4 cases) of papillary neoplasm of low malignant potential, 47.9% (35 cases) of urothelial carcinoma of low grade, and 46.6% (34 cases) in urothelial carcinoma of high grade were reclassified using the WHO/ISUP consensus classification. Histologic grades based on two grading systems were correlated to invasion and stage (p<0.05). DNA topoisomerase II-alpha, Ki-67, and apoptotic indices were correlated to histologic grades based on two grading system and invasion. Also, the correlation of DNA topoisomerase II-alpha and Ki-67 indices, and DNA topoisomerase II-alpha and apoptotic indices were significant, respectively.
CONCLUSIONS
DNA topoisomerase II-alpha appears to be an useful marker for assessing the proliferation potential of urothelial carcinoma of in the urinary bladder.

Case Report

A Metastatic Granulocyte Colony-Stimulating Factor Producing Sarcomatoid Carcinoma of the Lung Causing Jejunal Intussusception: Report of a Case.: Min Eui Hong, Soon Auck Hong, Gui Young Kwon, Tae Jin Lee, Eon Sub Park, Sung Jae Cha, Jae Hyuk Do, Jae Hyung Yoo; Korean J Pathol. 2011;45(2):205-208.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.205

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Abstract PDF: A 75-year-old man was referred to our hospital with intestinal obstruction caused by intussusception. Abdominal computed tomography (CT) revealed seven polypoid masses in the small intestine, while chest CT revealed a mass in the right lower lobe. Preoperative laboratory tests showed white blood cell (WBC) and neutrophil differential counts of 63,630/mm3 and 95%, respectively. The serum granulocyte colony-stimulating factor (G-CSF) was 114 pg/mL, which was elevated (normal range, <18.1 pg/mL). After resection of the small bowel, the WBC count decreased to 20,510/mm3. The pathology showed a poorly differentiated carcinoma with sarcomatous components confirmed by positive immunostaining of cytokeratin (AE1/AE3) and vimentin in the small intestine. Furthermore, immunohistochemistry with specific monoclonal antibodies against G-CSF was positive. A lung biopsy revealed the same histological findings as the small intestine lesion. Therefore, the patient was diagnosed as having a G-CSF producing sarcomatoid carcinoma of the lung with metastasis to the small intestine.

Original Articles

Correlation of Expression of E-Cadherin, alpha-Catenin, beta-Catenin, and Clinicopathologic Parameters in Colorectal Adenocarcinomas.: Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2000;34(4):264-272.

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Abstract PDF: The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.

Expression of Glutathione S-Transferase, E-Cadherin, and Catenins during N,N-Diethylnitrosamine-Induced Hepatocarcinogenesis in Rat Liver.: Hyoung Joong Kim, Yon Sik Yoo, Tae Jin Lee, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2000;34(12):982-993.

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Abstract PDF: N,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells. To evaluate the role of adhesion molecules (E-Cadherin, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas. These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepato carcinogenesis.

Expression of p53, p21waf1/cip1, Cyclin D1 and Rb in Gastric Epithelial Proliferative Lesions.: Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2002;36(4):222-231.

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Abstract PDF: BACKGROUND
Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied.
METHODS
The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs).
RESULTS
The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs. Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044).
CONCLUSIONS
The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs. Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.

HER-2/neu Oncogene Amplification by Chromogenic in situ Hybridization and Immunohistochemical Expression of Topoisomerase II-alpha in the Breast Cancer.: Tae Jin Lee, Hyung Goon Oh, Gui Young Kwon, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2003;37(1):26-34.

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Abstract PDF: BACKGROUND
Amplifications of the HER-2/neu oncogene and the Topoisomerase II-alpha gene are important determiners of the response to chemotherapy in the breast cancer. For detecting HER-2/neu amplification, fluorescent in situ hybridization and immunohistochemistry are currently regarded as standard methods. Chromogenic in situ hybridization (CISH) is investigated as a new modification of in situ hybridization. The purpose of this study is to compare the efficacy of CISH and immunohistochemistry (IHC) in detecting HER-2/neu oncogene amplification and to investigate the prognostic significance of the HER-2/neu oncogene and the Topoisomerase II-alpha gene in breast cancer.
METHODS
Using CISH and IHC the amplifications and protein expressions of the HER-2/neu oncogene were studied on paraffin sections of 43 infiltrating duct carcinomas. The expression of the Topoisomerase II-alpha gene was studied immunohistochemically.
RESULTS
Of the 43 infiltrating duct carcinomas, amplifications of the HER-2/neu oncogene by CISH were observed in 8 cases (18.6%), and the HER-2/neu protein was deemed overexpressed by IHC in 9 cases (20.9%). The amplifications of the HER-2/neu oncogene showed a statistically significant correlation with tumor size, histological grade, and the Topoisomerase II-alpha index. The Topoisomerase II-alpha index showed a statistically significant correlation with tumor size, lymph node status, stage, histologic grade, and estrogen receptor status.
CONCLUSIONS
CISH is a useful alternative for determining HER-2/neu amplification, especially for confirming the immunohistochemical staining results. HER-2/neu amplification and the Topoisomerase II-alpha gene index may be prognostic factors of breast cancer.

Case Report

Intravascular Leiomyosarcoma of the Femoral Vein: A Case Report.: Soon Auck Hong, Min Eui Hong, Gui Young Kwon, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2008;42(4):232-235.

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Abstract PDF: Intravascular leiomyosarcomas of the femoral vein are extremely rare. Our patient was initially diagnosed with a deep vein thrombosis based on ultrasonography and venography. The thrombectomy specimen consisted of typical spindle cells with variable anaplasia arranged in a fasciculating and interlacing pattern. The final diagnosis was proved to be an intravascular leiomyosarcoma confirmed by immunohistochemical studies for smooth muscle actin, desmin, vimentin, CD34 and CD68.

Original Articles

Expression of Cyclins (D1, A, E, and B1) in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Bladder Carcinogenesis.: Gui Young Kwon, Eon Sub Park, Sung Geun Bong, Tae Jin Lee, Mi Kyung Kim, Jae Hyung Yoo, Kye Yong Song; Korean J Pathol. 2003;37(4):255-262.

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Abstract PDF: BACKGROUND
Cell cycle deregulation plays a major role in chemical multistage carcinogenesis.Therefore, the evaluation of cell cycle proteins is important.
METHODS
In order to induce carcinogenesis in the rat urinary bladder, 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)was administered to male Sprague-Dawley rats for 30 weeks. Expressions of cyclin D1, A, E, and B1 were examined by immunohistochemical stainings.
RESULTS
Urothelial cell hyperplasia appeared at 5 weeks, followed by papilloma at 10 weeks. Superficial carcinoma was observed at 20 weeks, and invasive carcinoma developed in 40% (4/10) of the rats at 30 weeks. Expressions of cyclin D1 and A increased sequentially from normal mucosa throughhyperplasia, papilloma, and carcinoma (p<0.01). Expressions of cyclin D1, B1 and cyclin Ewere higher in invasive carcinomas than in superficial carcinomas (p<0.01). In contrast, therewas no significant difference in the expression of cyclin B1 between hyperplasia, papillomaand superficial carcinoma.
CONCLUSIONS
The present results indicate the important roles of cyclin D1 and A in the development of BBN-induced urothelial carcinoma of rats. Aberrantexpression of cyclin B1 and E may contribute to the progression from superficial to invasivebladder cancer rather than tumorigenesis.

Inflammatory Gastric Adenocarcinoma with Neutrophil Leukcytosis.: Eon Sub Park, Yong Il Kim; Korean J Pathol. 1993;27(2):195-197.

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Abstract PDF: A 36-year-old man received a subtotal gastrectomy for Borrmann type 2 advanced carcinoma in the antrum of the posterior well. Preoperatively, peripheral white blood cell count was 16,400/mn3 with 80% of neutrophils. Microscopically, the tumor was of a poorly differentiated adeocarcinoma with intense eutrophilic infiltration which was totally confined within the neoplastic portion and in the metastatic focus in the regional lympho nodes. Repeated postoperative whits blood cell counts dropped down to the normal level. Neither infectious nor knowledge, this is the first case of gastric carcinoma with massive neutrophilic stromal reaction(inflammatory carcinoma) and leukocytosis in the literature in the korea.

Negri Bodies in Rabid Dog: Light and Electron Microscopic Findings.: Eon Sub Park, Young Uk Park, Jae Hyung Yoo, Kye Yong Song, Je G Chi; Korean J Pathol. 1992;26(6):615-619.

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Abstract PDF: Rabies is a fetal viral encephalitis to which all mammals, including man are susceptible. This virus, the genus of Rhabdovirus, is usually present in the saliva of infected animals and is transmitted by their bite. As a rule the virus enter the CNS by ascending along peripheral nervous system and extremely variable in extent. Negri bodies are appear in about 75% of cases. These bodies are eosinophilic, usually rounded inclusions and is located in the cystoplasm of the neurons, most frequently in the pyramidal neurons of the Hippocampus and the Purkinje cells of the cerebellum. We have experienced a case of canine rabies that showed Negri bodies in the Purkinje cells along with diffuse degenerative encephalitis and perivascular mononuclear cells infiltration. The Negri bodies were best demonstrated by Negri body staining although routine H-E staind was also useful. There inclusion bodies were located exclusively in the cytoplasm, and were found occasionally. Electron microscopic findings of the Negri bodies showed aggregates of bulletshaped nucleocapsids. We report a Negri body found in the brain of rabid dog with the light and electron microscopic findings.

Renomedullary Interstitial Cell Tumor.: Eon Sub Park, Mi Kyung Kim, Jae Hyung Yoo, Kye Yong Song; Korean J Pathol. 1989;23(3):371-373.

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Abstract PDF: We present an ultrastructure of an incidentally found renomedullary interstitial tumor also called as medullary fibroma in a 77 year-old female who had a metastatic adenocarcinoma of colon to the ureter. This tumor was a small and grayish white nodule in renal medulla, measuring 0.4 x 0.4 cm. Microscopically the tumor composed of spindle cells, with some vacuolation and intercellular collagen fibers. The electron microscopic observation of the spindle cells reveal that nuclei are spindle to oval shape and cytoplasm contain abundant rough endoplasmic reticulum, polyribosome without microfilaments and cisterna like structures supporting that the renomedullary interstitial cell tumor is renal interstitial cell origin than fibroblasts.

Serochemical and Histopathological Observations on the Effect of Malotilate in Chronic Liver Injury Induced by Carbon Tetrachloride with or without Ethanol.: Hyoung Chun Kim, Eon Sub Park, Jae Hyung Yoo, Kye Yong Song; Korean J Pathol. 1989;23(2):223-234.

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Abstract PDF: An experimental studies were carried out to observe the protective effects of malotilate, a new antihepatotoxic agent, on the chronic hepatic injury induced by CCl4 with or without ethanol. The rats used weighed about 200g were divided into 2 groups, 4 weeks & 8 weeks. Each group was given by orally with malotilate, 100 mg/kg, once a day, and was injected by subcutaneously with CCl4 1.5 mg/kg in a mixture with olive oil twice a week. Aqueous ethanol (20%) was administered in drinking water daily. The serochemical and histopathological studies were carried out in each experimental group. The results were as follows: 1. The chronic liver injuries induced by CCl4 with or without ethanol were significantly ameliorated by normalize serum values GOT, GPT. Alkaline phosphatase, Cholesterol, HDL-Cholesterol, and gamma glutamyl transpeptidase. 2. In Group of 4 weeks, malotilate manifested protective effects by significant inhibition of fatty changes, spotty necrosis and fibrosis in CCl4-intoxicated liver with or without additional ethanol. 3. In group of 8 weeks, malotilate significantly imoproved fatty changes, fibrogenic activity in the group administered with CCl4, followed by ethanol.

Immunohistochemical Observation on the Plasma Cells Secreting Specific and Non-specific Anti-body to Parasite in Soft Tissue Cysticercosis.: Eon Sub Park, Suk Il Kim, Kye Yong Song; Korean J Pathol. 1988;22(4):367-374.

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Abstract PDF: In order to elucidate the possibility of diagnosis in soft tissue cysticercosis in case no parasite in it, immunohistochemical staining with antihuman IgG, IgM, and IgA and anticysticercus antibody in tissue section were carried out. Not only the differential counts of infiltrated plasma cells but also the parasite itself against to the anticysticercus antibody were observed. Materials stained immunohistochemically were consisted of 21 soft tissue cysticercosis with or without parasite. The results were as follows: 1) IgG producing plasma cells were most frequent (45.8+/-18.7) and followed by IgM (14.3+/-0.43) and (4.3+/-5.71). Number of IgG plasma cells were more frequently accompanied in the presence of cysticercus (55.9+/-17.7) than in the absence of parasite (39.7+/-17.1). 2) The mean+/-S.D. of plasma cells positive to the anticysticercus antibody were 28.2+/-18.7. And anticysticercus antibody producing plasma cells were more frequent in the presence of cysticercus (49.2+/-5.16) than in the absence of parasite (15.2+/-9.46). 3) Antigenicity of the cysticercus was strong in inner layer(#) followed by tegument(+) and fibrous layer(-). 4) Therefore, it could be suggested that antibody against to the cysticercus is mainly produced by IgG plasma cells and antigenicity of the worm is strong in the inner layer of cyst wall. In addition, there is a possibility of assisting the diagnosis of cysticercosis with anticysticercus antibody by immunohistochemically.

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