Journal of Pathology and Translational Medicine

Volume 37(5); October 2003

Original Articles

Second Opinion Diagnostic Discrepancy in Surgical Pathology: Asan Medical Center Experience.: Young Min Kim, Kyung Ja Cho, Sun Young Jun, Mi Sun Choe, Shin Kwang Khang, Jae Y Ro; Korean J Pathol. 2003;37(5):301-306.

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Abstract PDF: BACKGROUND
Review of the outside pathology material is an important practice that provides useful information on patient managements and improves the diagnostic quality in surgical pathology. We report our experience with the frequency and types of diagnostic discrepancies in patients referred to the Asan Medical Center for treatment or a second opinion.
METHODS
All referral pathology diagnoses (867 surgical cases) made from October 2001 to July 2002 at Asan Medical Center were compared with outside pathology diagnoses.
RESULTS
Of the 867 surgical cases reviewed, 231 (26.7%) cases had a diagnostic discrepancy, which included 49 (5.7%) major and 182 (21.0%) minor discrepancies. The contents of the major discrepancies were a change in the diagnosis (34 cases), a change in the type of malignancy including small cell carcinoma and non-small cell carcinoma of the lung (10), a diagnosis of a metastasis as the primary lesion (4), and errors in interpreting the invasiveness (1). The causes or reasons for the major discrepancy were a difference in interpretation (81.6%), the availability of special studies (10.2%), a failure to identify the lesions (4.1%), and a lack of clinical information (4.1%).
CONCLUSIONS
The major discrepancy rate (5.7%) was comparable to that of the other reports from western countries. Among the major discrepancies, a change in diagnosis was most commonly observed and difference in interpretation was the most common reason. A routine review of all the patients pathology material is recommended for all referral patients for an improvement in the pathologic diagnoses and to provide better medical care.

Effects of Calcitriol on Delayed Neuronal Damage of Hippocampus in Transient Global Ischemia Model of Mature Gerbil.: Hye Jin Park, Hea Soo Koo, Woon Sup Han, Kyung Kyu Choi; Korean J Pathol. 2003;37(5):307-315.

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Abstract PDF: BACKGROUND
It is well documented that calcium ions perform a major role in neuronal degeneration in cerebrovascular disease and the other degenerative diseases, and that 1,25-dihydroxyvitamin D3 (D3) has the dose-dependent protective effects. This study was performed to examine the effects of different D3 dosages against delayed neuronal damage of the hippocampus.
METHODS
Mature mongolian gerbils were injected with either 0.8 microgram/kg/day (group 2) for 5 days or 1.0 microgram/kg/day for 8 days (group 3) prior to the 10 min ligation of the bilateral common carotid arteries. Immunohistochemical expression for the glial cell line-derived neurotrophic factor (GDNF), the basic fibroblast growth factor (bFGF) and the platelet-derived neurotrophic factor (PDNF) was observed in the D3-injected (0.8 microgram/kg/day for 5 days) group.
RESULTS
Group 2 showed a highly significant attenuation of delayed neuronal damage in the lateral CA1 region at 7 days after reperfusion. Group 3 showed unilateral or bilateral hemispheric infarcts 24 h after the onset of reperfusion. The D3-injected group showed a markedly increased bFGF expression level.
CONCLUSION
The dose-dependent effect of D3 suggests the importance of determining the appropriate D3 dose for clinical applications. Although the mechanism(s) of neuroprotection by D3 remains unclear, D3 may facilitate a reduction in ischemia-induced oxidative stress via the activation of the neurotrophic factors, including bFGF and GDNF.

Squamous Cell Carcinoma Arising in Mature Cystic Teratoma of the Ovary: a Report of Six Cases and Immunohistochemistry of the p53 Protein and p21WAF1/CIP1.: Kyung Hee Kim, Kwang Sun Suh, Joo Heon Kim, Dong Wook Kang, Dong Hoon Kim, Seong Ho Kim, Jong Ho Back, Mee Ja Park; Korean J Pathol. 2003;37(5):316-319.

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Abstract: BACKGROUND
Mature cystic teratoma is a common type of ovarian tumor. Although squamous cell carcinoma (SCC) is the most common carcinoma in malignant transformations of ovarian mature cystic teratomas, SCC arising in a mature teratoma is rare.
METHODS
This paper reports four cases of invasive SCC, a case of an adenosquamous cell carcinoma and a case of a pure in situ SCC arising in a mature cystic teratoma including a clinicopathological evaluation and an immunohistochemical study of the p53 protein and p21WAF1/CIP1.
RESULTS
The mean age of the patients was 60 years. The sizes of the mature cystic teratomas in all cases were greater than 7.5 cm in the largest diameter. Five cases showed the nuclear accumulation of the p53 protein with no p21WAF1/CIP1 immunoreactivity. The other case showed the nuclear accumulation of p21WAF1/CIP1 without p53 expression. There was a significant inverse relationship between the p53 protein level and p21WAF1/CIP1 expression.
CONCLUSION
A clinicopathological evaluation showed that a SCC arising from a mature cystic teratoma must be included in a differential diagnosis when the patient is over 42 years of age and the size of a mature cystic teratoma is greater than 75 mm in the largest diameter. It is suggested that p53 overexpression is implicated in the malignant transformation, and the p21WAF1/CIP1 expression level is dependent on alterations in the level of the p53 protein in these tumors.

Studies of CD44s and CD44v6 Expressions and Correlation with Clinicopathologic Parameters in Gastric Carcinoma.: Zhu Hu Li, Zhen Hua Lim, Ho Jong Jeon; Korean J Pathol. 2003;37(5):320-324.

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Abstract PDF: BACKGROUND
The aim of this study is to elucidate the relationship between the CD44s and CD44v6 expression level and the biological characteristics of a gastric carcinoma.
METHODS
CD44s and CD44v6 expression was investigated in 56 gastric carcinomas, 18 dysplasias, and 22 normal mucosae by immunohischemical staining.
RESULTS
The CD44s and CD44v6 expression rates in gastric carcinomas, dysplasia, and normal mucosae were 80.3% and 83.9%, 72.2% and 77.8%, and 13.6% and 4.5%, respectively. Statistical analysis showed significant difference after comparing a gastric carcinomas and dysplasia to the normal mucosae (p<0.001). The CD44s and CD44v6 expression rates in the cases with invasion to the muscle proper and serosa were 60.7% and 57.1%, and 82.4% and 88.2%, respectively. Both showed a significant statistical difference compared to the expression rates in the cases with invasion to the mucosae and submucosae. The CD44s and CD44v6 expression rates in gastric carcinomas with a lymph node metastasis showed a statistically significant difference compared to those without a lymph node metastasis (p<0.001 and p<0.01, respectively). CD44s and CD44v6 were also expressed in the normal basal cells around gastric carcinomas.
CONCLUSIONS
The CD44s and CD44v6 expression showed a significant relationship with gastric carcinogenesis, toward an aggressive biologic behavior.

Immunohistochemical Study of p27Kip1 Expression in Gastric Adenomas and Early Gastric Carcinomas: Analysis of 65 Cases.: Na Hye Myong; Korean J Pathol. 2003;37(5):325-332.

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Abstract PDF: BACKGROUND
Recent studies have suggested that loss of p27Kip1 expression correlates with poor prognosis in gastric carcinomas, although the published data is still controversial. However, there are very few reports on the immunohistochemical expression of p27Kip1 in gastric adenomas and its significance in the progression of gastric adenomas to early gastric carcinomas (EGCs) is unclear. We therefore performed an immunohistochemical study for p27Kip1 expression in gastric adenomas with low- and high-grade dysplasia and EGCs to investigate the role of p27Kip1 expression in gastric carcinogenesis.
METHODS
We collected 45 cases of endoscopic mucosal resection specimens which were diagnosed as gastric adenomas and 20 cases of gastrectomy specimens showing EGCs. Using a monoclonal antibody against p27Kip1, the im- munohistochemistry was performed on paraffin-embedded specimens.
RESULTS
The loss of p27Kip1 immunoreactivity (<5% of the tumor cells) tended to be observed more frequently in high-grade adenomas than in the low-grade. The loss was found significantly higher in the EGCs than in both high-grade and low-grade adenomas (p=0.000). Gastric adenomas with villous component showed significant loss of p27Kip1 expression (p=0.057).
CONCLUSION
These results suggest that loss of p27Kip1 expression can play a role in the progression of gastric adenomas into adenocarcinomas and the villous component allows reliable estimation of the possibility for malignant transformation.

Analysis of Expression of p63 in Cervical Neoplasia Comparing with Other Immunohistochemical Markers .: Min Yeong Kim, Sam Hyun Cho, Moon Hyang Park; Korean J Pathol. 2003;37(5):333-341.

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Abstract PDF: BACKGROUND
The reproducibility in grading a cervical intraepithelial neoplasia (CIN) are not perfect. The aim of this study was to assess the value of the immunohistochemical expression of p63 and the other biomarkers for grading a CIN (dysplasia and in situ carcinoma), and diagnosing invasive carcinomas.
METHODS
Sixty six cervical specimens were immunostained with the monoclonal antibodies against p63, Ki-67, p27Kip1, and p53 to determine the localization.
RESULTS
The p63 positive cells are well linked with squamous cell maturation and the degree of dysplasia. In mild dysplasia, the p63 positive cells were localized to the basal and parabasal cells, which gradually extended into the middle and upper layers in moderate and severe dysplasia. p63 expression was strong in immature squamous epithelium and invasive squamous cells, but was constantly absent in an adenocarcinoma. The Ki-67 positive cells were scattered from the parabasal cells to the superficial cells in accordance with the degree of dysplasia. p27Kip1 expression was noted in the intermediate cells in the normal cervix. In CIN, the p27Kip1 positive nuclei tended to extend to the basal cells, but it showed no diagnostic consistency in an invasive carcinoma. p53 expression was also variable.
CONCLUSION
p63 is a useful diagnostic adjunct for grading CIN as well as for detecting microinvasion and squamous differentiation in invasive carcinoma. However, immunohistochemical expressions for the p27Kip1 and p53 have no correlation with the grade of CIN and squamous cell carcinoma.

Pathologic Findings in the Liver of Hepatitis B Virus X Transgenic Mice.: Hyung Bae Moon, Dae Yeul Yu, Byung Jun So, Haak Cheol Kim, Won Cheol Han, Ki Jung Yun, Hyung Nyoon Yoo; Korean J Pathol. 2003;37(5):342-350.

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Abstract PDF: BACKGROUND
The aim of this study was to investigate the hepatic pathology of HBx transgenic mice.
METHODS
The gross and histological examinations were done in 125 HBx transgenic mice and 34 non-transgenic littermates.
RESULTS
The incidence of a hepatic tumor was in-creased in the HBx transgenic mice older than 7 months and the overall incidence of a hepatic tumor was 62.2% (51/82) in the 13-18 months group of the HBx transgenic mice. The size of the hepatic tumor was 2.06+/-.92 mm in the 7-12 months group and 4.94+/-.05 mm in the 13-18 months group of HBx transgenic mice. All hepatic tumors were hepatocellular carcinomas and the histological patterns of hepatocellular carcinoma were either solid (84.2%, 48/57) or trabecular (15.8%, 9/57). Dysplastic changes in the hepatocytes were evident in 59.2% (74/125) of the HBx transgenic mice. There was lymphocyte infiltration, necrosis, fatty metamorphosis in both the dysplastic and tumor areas of the HBx transgenic mice. Vascular ectasia was identified in the tumor area of the HBx transgenic mice.
CONCLUSIONS
The pathological findings of the HBx transgenic mice were dysplastic changes in the hepatocytes and development of a hepatocellular carcinoma associated with lymphocyte infiltration, necrosis, fatty metamorphosis in the dysplastic area and tumor area of the HBx transgenic mice.

Case Reports

Endolymphatic Sac Tumor: A Case Report.: Dae Woon Eom, Jae Y Ro, Shin Kwang Khang, Chang Jin Kim, Kyung Ja Cho; Korean J Pathol. 2003;37(5):351-354.

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Abstract PDF: Endolymphatic sac tumor (ELST) is a very rare adenomatous tumor of the temporal bone histologically characterized by a typical papillary pattern. This tumor often shows a locally aggressive growth and recurrence despite its relatively benign histology. We report a case of endolymphatic sac tumor of the right jugular foramen in a 50 year-old male. Microscopically, the tumor was composed of uniform cuboidal to low columnar epithelial cells arranged in an arborizing papillary pattern. Under immunohistochemistry, the tumor cells were positive for cytokeratin, CD56, epithelial membrane antigen, neuron specific enolase, and vimentin.
Discussion
on the classification and histogenesis of adenomatous tumors of the middle ear and temporal bone has been active in western countries during the recent decades; however, these tumors have been very unusual in Korea. This is the second report of ELST in Korea, and consists of a discussion on related problems.

Congenital Epulis: A Report of Two Cases.: Hye Kun Oh, Chae Hong Suh; Korean J Pathol. 2003;37(5):355-357.

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Abstract PDF: We present two cases of congenital epulis in female newborns. Congenital epulis is a very rare lesion of uncertain histogenesis. The present lesions were located on the gingiva of the anterior alveolar ridge of the maxilla and the mandible, respectively. Both tumors consisted mainly of large eosinophilic granular cells arranged in solid nests. The neoplastic granular cells showed positive reactions for neuron specific enolase and vimentin in their cytoplasms, while they were entirely negative for other antibodies used in this study.

Sudden Death from Cardiac Sarcoidosis: A Case Report.: Soo Kyoung Lee, Sun Zoo Kim, Yoon Seup Kum, Tae In Park, Sang Han Lee, Jong Min Chae, Jung Sik Kwak; Korean J Pathol. 2003;37(5):358-361.

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Abstract PDF: Sarcoidosis is a systemic granulomatous inflammation with an unknown cause. The commonly involved sites are the lymph nodes, lungs, skin, eyes, and heart. Although cardiac involvement in sarcoidosis is rarely detected clinically, it is reported in 20-50% of autopsied sarcoidosis patients. Cardiac involvement is one of the most severe conditions of sarcoidosis and may cause sudden death. We report a case of a sudden death due to a massive cardiac sarcoidosis in a 43-year-old man. The microscopic examination revealed an extensive noncaseating granulomatous inflammation in the mediastinal lymph nodes and the heart with no evidence of myocyte necrosis. A special stain and molecular study excluded the possibility of other causes such as fungi or mycobacterium. The authors concluded that the cause of death was attributed to arrhythmia due to a cardiac sarcoidosis with massive involvement of the conduction system.

Dedifferentiated Liposarcoma with a Peculiar Whorling Pattern: A Case Report.: Ji Shin Lee, Young Bog Kim; Korean J Pathol. 2003;37(5):362-364.

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Abstract PDF: A dedifferentiated liposarcoma is a uncommon neoplasm characterized by the coexistence of a well-differentiated liposarcoma and non-lipogenic sarcomas. A peculiar neural-like or meningothelial-like whorling pattern of dedifferentiation has recently been reported. We report a case of dedifferentiated liposarcoma with a peculiar whorling pattern in the scrotum of a 76-year-old man. Histologically, the tumor consisted of areas of a well differentiated liposarcoma admixed with areas of a morphologically non-lipogenic sarcoma. The whorls were scattered throughout the tumor. The cells in the whorls and dedifferentiated area showed a significant nuclear PCNA and p53 protein reactivity.

Bilateral Mammary Metastasis of Alveolar Soft Part Sarcoma: A Case Report.: Soo Youn Cho, Ho Chang Lee, Chong Jai Kim, Min Suk Kim, Sun Hoo Park, Eui Keun Ham, In Ae Park; Korean J Pathol. 2003;37(5):365-368.

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Abstract PDF: An alveolar soft part sarcoma(ASPS) is a rare malignant soft tissue tumor, which metastasizes to the lung, bone and brain. Recently, we encountered an unusual case of a metastatic ASPS to the bilateral breasts in a 27-year-old woman. She had undergone surgery for an ASPS in her right thigh two years ago, which metastasized to the breast on three occasions, 15 months, 20 months and two years after surgery.

Silica Granuloma after Intermittent Intramuscular Injections: A Case Report.: Suk Jin Choi, Jong Im Lee, Jung Ran Kim, Tae Jung Jang, Ki Kwon Kim, Phil Hyun Chung; Korean J Pathol. 2003;37(5):369-372.

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Abstract PDF: Most silica-contaminated wounds of the skin heal without complications. Cutaneous silica granuloma is a poorly understood, uncommon condition resembling a sarcoidosis. We report a case of silica granuloma after intermittent intramuscular injections. A 70-year-old man presented a painless mass in his right buttock for 2 weeks. He had received intermittent intramuscular injections of antihistamine drugs due to chronic dermatitis for 30 years. The histolopathological findings showed numerous hyalinized collagenous nodules with concentric layers, and an ill-defined chronic granulomatous inflammation containing foreign material. A polarized light microscopic examination revealed birefrigent particles. The presence of silica components was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis.

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