Journal of Pathology and Translational Medicine

Volume 39(3); June 2005

Original Articles

Pathology Teaching for the Undergraduate Students in Korean Medical Schools: Current Debates and Future Program Design.: Yong Il Kim; Korean J Pathol. 2005;39(3):145-150.

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Abstract PDF: This article aimed to summarize the current critiques or debates on the pathology teaching for the undergraduate medical students in Korean medical schools and to rationalize the curricular approaches for renovation and instructional strategies which are under the hot discussion. Of 41 medical schools in Korea, most pathology programs have been criticized along the line of their traditional discipline-oriented, teacher-centered curriculum and morphologydirected instruction by their limited emphasis of developing either the reasoning abilities or the effort for the systematic understanding of disease mechanism, while any measures of compensatory strategies against the declining participation to the autopsy remain unqualified. The formal instruction of the pathology course was also under the strong debates in regard to the driving effort in teaching every corners of the textbook contents aside from the overemphasis of rather monotonous and less dynamic microscopic observation equipped with the sketch-based laboratory works. Also, student's loss of interest on pathology and other concerns neglected during the undergraduate pathology course was discussed. The author stressed the leadership of the pathology course among other biomedical disciplines especially in development of the appropriate educational curricula such as the horizontal vs. vertical integrated teachinglearning process and tutorials. Alternative emphasis was made on more experimental experiences as a part of upgrading the reasoning power together with the simulated case studies prior to the senior class to meet the school objectives.

Expression of Survivin in Non-Small Cell Lung Carcinoma: Relationship to Tumor Biology and Prognosis in Surgically Treated Patients.: Min Jung Jung, Bong Kwon Chun; Korean J Pathol. 2005;39(3):151-157.

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Abstract PDF: BACKGROUND
Survivin, a novel member of inhibitor-of-apoptosis, is undetectable in most terminally differentiated nonproliferative adult tissue, but is overexpressed in some human malignancies. The survivin gene expression is repressed by binding of wild-type p53 with the survivin promotor. In this study, we investigated the prevalence of survivin expression, its association with p53 overexpression and proliferative index, and clinicopathological significance in non-small cell lung carcinomas (NSCLC).
METHODS
Immunohistochemical stainings were performed in 59 cases of primary NSCLC for survivin, p53 and Ki-67. Correlations between the survivin expression, p53 overexpression and Ki-67 labeling index were analyzed.
RESULTS
Survivin expression was detected in 47 carcinomas (80%) with nuclear immunoreactivity (56%). Survivin nuclear immunoreactivity revealed significantly worse prognosis in NSCLC patients (p=0.003), and correlated with lymph node metastasis (p=0.014), lymphovascular invasion (p=0.032), p53 overexpression, and Ki-67 labeling index (KI 24.2 +/- 6.9, p=0.045). Survivin expression was not correlated with histological type and pT status.
CONCLUSIONS
High incidence of survivin overexpression in NSCLC suggests that survivin is involved in lung carcinogenesis, and nuclear expression of survivin can be used as a poor prognostic predictor in NSCLC patients. Expression of mutant p53 seems to be a possible mechanism of survivin up-regulation in NSCLC.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

Questionable Role of Human Herpesvirus-8 in the Pathogenesis of Multiple Myeloma.: Min Sun Cho, Shi Nae Lee; Korean J Pathol. 2005;39(3):164-167.

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Abstract PDF: BACKGROUND
Human herpesvirus 8 (HHV-8) has been strongly implicated in the etiopathogenesis of multiple myeloma. Cytokines, especially interleukin-6, that are produced by HHV-8 infected bone marrow stromal cells may play a role in the proliferation of neoplastic plasma cells. Viral DNA sequences have been detected in the bone marrow and peripheral blood cells of myeloma patients. Yet some investigators have not found the same results.
METHODS
We exmined the presence of HHV-8 DNA in the paraffin-embedded cell block specimens of bone marrow aspirations from 26 patients with multiple myeloma by polymerase chain reaction (PCR) with KS330(233) primers. Thirteen cases of bone marrow aspirations from patients with other diseases were used as a negative control. The DNA extracted from the BC-1 cell line was used as a positive control. Immunohistochemistry using commercially available HHV-8 antibody was done in the cases that were proven HHV-8 DNA-positive by PCR.
RESULTS
One case (3.9%) among the 26 patients with myleoma was positive for HHV-8 DNA by PCR, but no positive cells were detected in this case by immunohistochemistry.
CONCLUSIONS
We could not find a clear relation between myeloma and HHV-8 in Korean patients examined in the present study.

Mutational Analysis of Proapoptotic bcl-2 Family genes in Colon Carcinomas.: Young Hwa Soung, Jong Woo Lee, Su Young Kim, Suk Woo Nam, Won Sang Park, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee; Korean J Pathol. 2005;39(3):168-171.

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Abstract PDF: BACKGROUND
Several lines of evidence have indicated that the deregulation of apoptosis is involved in the mechanisms of cancer development, and somatic mutations of the apoptosisrelated genes have been reported in human cancers. Members of the bcl-2 family proteins regulate the intrinsic apoptosis pathway mainly in the mitochondria. The aim of this study was to explore whether the somatic mutation of the proapoptotic bcl-2 family genes, one of the mechanisms that prolong the survival of cancer cells, occurred in colorectal carcinomas.
METHODS
In the current study, to detect the somatic mutations in the DNA sequences encoding the bcl-2 homology 3 (BH3) domain of the human bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G, and bmf genes in 98 colon adenocarcinomas, we used polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP), and DNA sequencing.
RESULTS
The SSCP analysis detected no evidence of somatic mutations of the genes in the coding regions of the BH3 domain in the cancers.
CONCLUSIONS
The data presented here indicate that the proapoptotic bcl-2 family genes, bak, bid, bik, bim, PUMA, bcl-rambo, bcl-G and bmf may not be somatically mutated in human colorectal carcinomas, and suggest that the colorectal cancers may not utilize mutational events of these proapoptotic bcl-2 family genes in the mechanisms for evading apoptosis.

Comparison of the Expression of Variants of CD44 between Node-positive and Node-negative Breast Carcinomas.: In Ae Park, Ho Chang Lee, Soo Youn Cho; Korean J Pathol. 2005;39(3):172-180.

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Abstract PDF: BACKGROUND
The purpose of this study is to determine the value of CD44 and its splice variants as markers for the metastatic potential of infiltrating ductal carcinomas of the breast.
METHODS
Tissue samples of infiltrating ductal carcinoma of the breast were examined for the expression of standard CD44 (CD44H) and s CD44 isoforms, v3, v4-5 and v6 in 41 node-positive and 31 node-negative cases. The immunohistochemistry results were correlated with other clinicopathologic parameters, and these results were correlated with accompanying high grade and non-high grade DCIS areas of the tumors in both node-positive and node-negative cases.
RESULTS
The expression of CD44 in the invasive tumor areas and in the metastatic foci of the lymph nodes showed a statistically significant correlation. The expression of CD44H in the invasive tumor areas and the DCIS area showed a statistically significant correlation in the lymph node (-) group. There was statistical significance between the CD44 H and CD44v3 expressions and the histologic grade of the invasive tumor in the cases with positive lymph nodes. There was no statistical significance between CD44 expression and lymph node metastasis, tumor size and type of tumor margin.
CONCLUSIONS
We conclude that changes in the CD44 expression in breast cancer occur early in breast carcinogenesis, and this is involved in tumor differentiation, but we could not establish any correlation between the expression of the CD44 variant isoforms and the metastasis of breast cancer.

Clinicopathologic Features of Granulomatous Mastitis.: Yee Jeong Kim, Yoon Jung Choi, Ji Young Kim, Hee Jung Kim, Yang Soon Park, Soon Won Hong, Chanil Park, Doyil Kim, Hyde Lee, Woo Hee Jung; Korean J Pathol. 2005;39(3):181-186.

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Abstract PDF: BACKGROUND
Granulomatous mastitis (GM) is a rare chronic inflammatory condition that clinically mimics a carcinoma. The diagnosis of idiopathic GM depends on the exclusion of other granulomatous inflammations. The purpose of this study is to correlate the clinicopathological features of GM with etiologies.
METHODS
We reviewed the clinical records of 58 cases that were histologically diagnosed as GM. We performed special stains for microorganisms such as Ziehl-Neelsen, periodic acid Schiff and gram stains, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis (TB PCR).
RESULTS
The mean age of patients was 35.3 years. Most patients were parous except three. Seven patients (12.1%) were related with pregnancy or lactation. TB PCR was positive in nine patients (15.5%). Five patients (8.6%) had gram positive bacilli that were recognizable as coryneform bacteria. Culture study demonstrated Staphylococcus aureus in only one case. Infectious GM had a greater tendency to form abscesses. Fat necrosis was more likely to be present in idiopathic GM, but other histological features were similar to each other. Twenty-two cases (37.9%) showed recurrence.
CONCLUSIONS
We suggest that TB PCR and gram stain are essential tests for the differential diagnosis of GM, because the histologic features considerably overlap irrespective of the various etiologies.

E-cadherin Expression Loss in T1 Invasive Ductal Carcinoma of the Breast as a Predictive Marker for Lymph Node Metastasis.: Eun Kyung Kim, Aysegul Sahin; Korean J Pathol. 2005;39(3):187-191.

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Abstract PDF: BACKGROUND
E-cadherin is a transmembrane glycoprotein, which has been shown to mediate calcium-dependent epithelial cell adhesion. A loss of E-cadherin expression has been associated with the tumor invasion and metastatic potential in some human cancers. The objective of this study was to evaluate E-cadherin expression in T1 breast ductal carcinomas in order to determine whether the loss of E-cadherin expression is correlated with lymph node metastasis.
METHODS
One hundred seventy nine patients with breast invasive ductal carcinoma, measuring less than 2 cm, were enrolled in this study. The subjects were divided into two groups on the basis of the status of the ipsilateral axillary lymph node, T1N1 (lymph node positive, n=91) or T1N0 (lymph node negative, n=88). None of the patients in this study had undergone preoperative chemotherapy. Formalin-fixed paraffin-embedded tissue sections of the primary breast cancers were stained by immunohistochemistry, using a mouse monoclonal antibody against E-cadherin. E-cadherin expression was designated as either positive (complete membranous staining) or negative (absent or incomplete membranous staining).
RESULTS
Benign breast parenchyma adjacent to invasive carcinoma was positive for E-cadherin. The loss of E-cadherin expression in the tumor was observed in 42% of patients of the T1N1 group, and in 24% of the T1N0 group. There was a significant correlation between the loss of E-cadherin expression and lymph node metastasis in the examined breast invasive ductal carcinomas (p=0.011).
CONCLUSIONS
Our findings suggest that E-cadherin is an important molecule with regard to both tumor cell adhesion and metastasis, and its absence may constitue an early event in metastatic development. Therefore, E-cadherin may be a useful predictive marker for nodal metastasis in patients suffering from invasive ductal carcinoma.

Case Reports

Neuromuscular Choristoma of the Sciatic Nerve: A Case Report.: Sun Young Kim, Hyuck Po Kwon, Kyoung Duck Kwak, Kee Baek Ahn; Korean J Pathol. 2005;39(3):192-196.

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Abstract PDF: Neuromuscular choristoma is a rare benign tumor of the peripheral nerves. To the best of our knowledge, 21 cases have been reported to date. We describe here a 20-day-old female infant who presented with a buttock mass (4.5 x 4.1 x 3.2 cm on MRI) arising from the left sciatic nerve. Microscopically, it was characterized by an intimately disorganized mixture of nerve fibers and striated muscle fibers that were occasionally surrounded by the perineurium and separated by fibrous bands of varying thickness. In some areas, there appeared to be some cells in transitional forms between nerve fibers and muscle fibers, revealing variously positive expressions for S-100 protein in the muscular components. These findings are consistent with the hypothesis that neuroectodermal-derived Schwann cells can give rise to mature skeletal muscle. It appears that the fibrosis may be related to the degeneration of the neural components. The size of the mass on MRI has been unchanged during the 3-year follow-up period.

Aspergillous Hypophysitis: A Case Report.: Jeana Kim, Leeso Maeng, Je Hoon Lee, Kyoung Mee Kim, Anhi Lee, Chang Suk Kang; Korean J Pathol. 2005;39(3):197-199.

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Abstract PDF: Aspergillous hypophysitis is an unusual cause of sella turcica enlargement, and this malady has a clinical presentation as a pituitary tumor, and especially as a pituitary adenoma. We report here on a case of aspergillous hypophysitis that developed in a 37-year-old healthy woman. She first experienced a blurred vision with amenorrhea and galactorrhea. Three months later, the CT scan revealed an intrasellar mass. The patient underwent a transsphenoidal exploration of the sella turcica for a presumed pituitary tumor. Histologically, the pituitary displayed necrotizing granuloma with the acutely branching fungal hyphae of Aspergillus.

Mixed Liposarcoma: A Case Report.: Jeung Il Kim, Hyun Jeong Kang, Kyung Un Choi; Korean J Pathol. 2005;39(3):200-202.

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Abstract PDF: True mixed liposarcomas are extremely rare tumors. We report here on a case of mixed liposarcoma that was composed of well differentiated and pleomorphic liposarcoma. A 76-year-old man presented to us with a mass in his left upper arm. This lesion had been there for twenty years, it was recently growing rapidly and had doubled in size during the recent 2 months. The MR image showed a mass composed of a fat component and a soft tissue component with necrosis. The old fat component was revealed as well differentiated liposarcoma, and the recent growing soft tissue component was revealed as pleomorphic liposarcoma. The two components showed different immunohistochemical results for MDM2.

Multiple Atypical Adenomatous Hyperplasia Mimicking Lung to Lung Metastasis: A Case Report.: Sung Hwa Bae, Kyung Jae Jung, Jong Yup Bae; Korean J Pathol. 2005;39(3):203-206.

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Abstract PDF: Atypical adenomatous hyperplasia (AAH) is regarded as a precancerous lesion in the multistep process for carcinogenesis of pulmonary adenocarcinoma. AAH is found in up to 25% of the lung tissue adjacent to cancer, particularly adenocarcinoma and also in 2-4% of autopsy cases. Until now, its main clinical significance is that some tumor recurrences are the lesions that have progressed from undetected AAH or they are newly developed cancers arising from AAH during the follow-up after the resection of adenocarcinoma. We present here the case of a 58-year-old woman having a large main adenocarcinoma with multiple small AAHs that mimicked lung-to-lung metastasis. AAH should be considered in the differential diagnosis of multiple small nodules during the preoperative evaluation and also during the follow-up of lung cancer patients.

Liposclerosing Myxofibrous Tumor in Tibia: A Case Report and Review of the Literature.: Jung Woo Choi, Young Seok Lee, Ju Han Lee, Han Kyeom Kim, Bom Woo Yeom, Jong Sang Choi, Hong Chul Lim, Chul Hwan Kim; Korean J Pathol. 2005;39(3):207-210.

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Abstract PDF: Liposclerosing myxofibrous tumor (LSMFT) is a benign fibro-osseous lesion that is characterized by a complex mixture of histologic elements, including its fibrous dysplasia-like features and its lipoma, myxofibroma, xanthoma and pseudo-Paget's bone patterns. However, this lesion is considered by some researchers as a variant of fibrous dysplasia or as the non-specific end result of degenerative change, while it is considered by others as a definite clinicopathologic entity. Here, we report on a case of LSMFT occurring in tibia, which is a very uncommon location for this tumor, and we review the related literatures. The case presented here shares features with those described for LSMFT, except for the location of this tumor. We believe that more studies on a larger scale that compare LSMFT with other benign bone lesions, including fibrous dysplasia, are required to clarify the origin and behavior of this lesion.

Plexiform Fibrohistiocytic Tumor of the Neck: A Case Report.: Hyang Mi Shin; Korean J Pathol. 2005;39(3):211-213.

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Abstract PDF: Plexiform fibrohistiocytic tumor (PFT) is a rare, low-grade soft tissue tumor that occurrs primarily in children and young adults. The most common location of PFT is the upper extremity, and there are very few reports of PFT in the neck. We report here on a case of PFT presenting as a painless subcutaneous nodule in the neck of a 46-year-old woman. Histologically, this subcutaneous tumor was composed of a plexiform proliferation of histiocyte-like cells and fibroblast-like cells along with a few multinucleated osteoclast-like giant cells. Immunohistochemically, the tumor cells were positive for vimentin, CD68 and smooth muscle actin (SMA).

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