Journal of Pathology and Translational Medicine

Volume 41(6); December 2007

Original Articles

Expression of Cyclin-Dependent Kinase-Associated Protein Phosphatase in Colorectal Carcinomas.: Chang Nam Kim, Soo Young Kim, Jae Wha Kim, Dong Wook Kang, Hyun Jin Son, Hye Kyung Lee, Mee Ja Park, Joo Heon Kim; Korean J Pathol. 2007;41(6):367-372.

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Abstract PDF: BACKGROUND
Cyclin-dependent kinase-associated phosphatase (KAP) is a human dual-specificity protein phosphatase that dephosphorylates Cdk2 on threonine160 in a cyclin-dependent manner and that is known as an up-regulated molecule in some malignant tumors. We investigated the expression and clinicopathologic significance of KAP protein in relation to tumorigenesis of colorectal carcinoma.
METHODS
The expression patterns of KAP protein in tumor tissue were examined by reverse transcription-PCR and immunohistochemical staining.
RESULTS
An enhanced transcriptional level of KAP mRNA was observed in 11 out of 12 colorectal carcinoma specimens. Immunohistochemical examination showed that KAP protein was more highly expressed in the tumors than that in the adjacent non-neoplastic mucosal tissues for 52 of 102 colorectal cancer tissues. The statistical analysis showed that an increased level of KAP protein in the colorectal cancer tissues was inversely correlated with the histologic grade, tumor size and Duke's stage.
CONCLUSION
The present study suggests that alteration of KAP might play a role, at least in part, in the tumorigenicity of colorectal carcinoma through the mechanism of cell cycle regulation.

Juvenile Ossifying Fibroma: A Clinicopathologic Study of 8 Cases and Comparison with Craniofacial Fibro-osseous Lesions.: Sohyung Park, Bong Jae Lee, Jeong Hyun Lee, Kyung Ja Cho; Korean J Pathol. 2007;41(6):373-379.

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Abstract PDF: BACKGROUND
Juvenile ossifying fibroma (JOF) is defined as a variant of the ossifying fibroma, and the latter includes juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). JOF can be distinguished from other craniofacial fibroosseous lesions by its tendency to recur and its clinical mimicry of malignant bone tumors, but some clinical and histological features of JOF overlap with the other fibro-osseous lesions as well. We aimed to identify the clinicopathologic definition of JOF.
METHODS
Forty-two cases of fibro-osseous lesions were reviewed and they were classified into JOF, fibrous dysplasia (FD) and ossifying fibroma (OF).
RESULTS
JTOF had long, slender and anastomosing trabeculae of osteoid in a fibrocellular stroma, and JPOF had small ossicles resembling psammoma bodies with a thick collagenous rim in the fibrous stroma, which are features that differ from those of FD and OF. Radiologically, JOF and OF showed a well-defined lesion but FD exhibited an ill-defined lesion. Clinically, the average age of the JOF patients was the youngest, followed by OF and FD. For JOF, three cases had rapid growth and two others showed recurrences. JOF mainly occurred in the paranasal sinuses, OF in the mandible and FD in any craniofacial bone.
CONCLUSION
We demonstrated the distinct characteristics of JOF and these features may be helpful for the diagnosis and management of this malady.

Analysis of Microsatellite Instability in Ovarian Epithelial Cancer.: Mee Young Sol, Kyung Un Choi, Jee Yeon Kim, Hyun Jeong Kang, Dong Hoon Shin, Ik Doo Kim, Hyo Seon Choi, Soon Jung Seo; Korean J Pathol. 2007;41(6):380-386.

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Abstract PDF: BACKGROUND
The aim of this study was to clarify the incidence and role of microsatellite instability (MSI) in sporadic ovarian epithelial cancers (OEC). We investigated the MSI status and mismatch repair (MMR) protein expression in OEC.
METHODS
MSI was examined by fluorescence- based polymerase chain reaction using five NCI panel markers (BAT25, BAT26, D2S123, D5S346 and D17S250) in 46 cases of OEC. Immunohistochemistry (IHC) for hMLH1 and hMSH2 was performed.
RESULTS
Seven cases (15.2%) exhibited high-frequency MSI (MSIH), one exhibited low-frequency MSI (MSI-L), and the remaining 38 demonstrated microsatellite stability (MSS). MSI-H in OEC was not associated with histologic grade, FIGO stage, tumor size, mitoses or histologic type. Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 7 (59.3%) MSI-H cases, whereas 4 of the 39 (10.3%) MSI-L or MSS tumors revealed loss of expression of MMR proteins. The sensitivity and specificity of immunohistochemistry for hMLH1 and hMSH2 were 57.1% and 89.7%.
CONCLUSIONS
Our data suggest that a genetic defect in the MMR system might play a role in the carcinogenesis of a minor subset of sporadic OEC however, immunohistochemical testing for hMLH1 and hMSH2 cannot accurately determine microsatellite instability status in OEC.

Clinicopathologic Analysis of Epidermal Growth Factor Receptor Status in Non-small Cell Lung Cancer: Protein Expression, Gene Amplification and Survival Analysis.: Seungkoo Lee, Jene Choi, Se Jin Jang; Korean J Pathol. 2007;41(6):387-392.

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Abstract PDF: BACKGROUND
Abnormal over-expression or gene amplification of epidermal growth factor receptor (EGFR) is important in the prognosis of non-small cell lung cancer (NSCLC). We investigated the frequency of EGFR protein expression and gene amplification, and the correlation between EGFR status and survival in NSCLC.
METHODS
We examined 360 cases of microarrayed NSCLC tissues for the EGFR protein expression and EGFR gene amplification using immunohistochemistry and fluorescent in situ hybridization.
RESULTS
EGFR protein expression and EGFR gene amplification occurred in 110 cases (30.6%) and 24 cases (6.7%), respectively. EGFR protein expression and gene amplification were more frequent in squamous cell carcinoma than in adenocarcinoma. Differences in EGFR protein expression did not dramatically affect survival curves (p=0.740), but differences in gene amplification did (p<0.05): EGFR gene amplification was associated with a lower 5-year survival rate.
CONCLUSION
EGFR protein expression and gene amplification showed moderate correlation with each other. EGFR gene amplification predicted a poor prognosis, whereas EGFR protein expression did not.

Anterior Neck Approach for 4-vessel Occlusion in Rats: A Study for Immunohistological Changes and the Effects of Aminoguanidine on Neuronal Cell Death in the Hippocampus.: Young Jun Ahn, Ki Young Choi, Gu Kang, Yong Seok Kim, Seungkoo Lee, Il Young Cheong, Keun Woo Kim; Korean J Pathol. 2007;41(6):393-405.

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Abstract PDF: BACKGROUND
Clinically relevant cerebral ischemia is encountered most frequently as a cardiac arrest or as single or multiple occlusions of the intracranial or extracranial cerebral arteries. Yamaguchi et al. has introduced a one-stage anterior approach to occlude the common carotid arteries (CCAs) and vertebral arteries (VAs).
METHODS
We used a 2-stage anterior approach for producing transient global ischemia by 4-vessel occlusion (4-VO). Four to five days after electrocauterization of two VAs using the anterior neck approach, two CCAs were clipped for 10 min under anesthesia. Aminoguanidine (100 mg/kg) was administered intraperitoneally immediately after 4-VO, and then twice a day for three consecutive days. Cresyl violet staining and immunohistochemical analysis for the expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were performed, using brain slices obtained from the rats that were sacrificed 1, 3, 5 and 7 days after reperfusion.
RESULTS
Aminoguanidine reduced neuronal cell death in the CA1 region of the hippocampus. Expression of GFAP, CD11b, nitrotyrosine, iNOS, and Bax were significantly increased in the CA1 region of the hippocampus three days after 4-VO.
CONCLUSIONS
We believe that modified 4-VO is a good method to study transient forebrain ischemia as it is simple and inexpensive to perform and can be utilized without stereotaxis, a pivoting dissection microscope, EEG, a laser flowmeter or the use of Mongolian gerbils.

Case Reports

Giant Retroperitoneal Lipomatous Angiomyolipoma Simulating Liposarcoma: A Brief Case Report.: Dakeun Lee, Joungho Han, Sung Joo Kim, Dongil Choi; Korean J Pathol. 2007;41(6):406-408.

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Abstract PDF: Extrarenal retroperitoneal angiomyolipomas (AML) are extremely rare, therefore they may present a diagnostic challenge. In this paper, the authors describe a case of a huge retroperitoneal AML in a 49-year-old woman who presented with sudden abdominal pain. Computed tomography revealed the presence of a large, round, fatty mass in the retroperitoneal space, which was easily removed by surgery. The mass was well encapsulated and dark yellow on the cut surface. Microscopically, the tumor was exclusively composed of adipose tissue with frequent multivacuolated, lipoblast-like cells masquerading as well differentiated liposarcoma. In addition, there were many clear, epithelioid cells present, especially around the small blood vessels, which were reactive for HMB-45 and smooth muscle actin.

Giant Fibrovascular Polyp of the Esophagus: A Case Report.: Ilseon Hwang, Jong lyel Roh, Young Hee Kim, Kyung Ja Cho; Korean J Pathol. 2007;41(6):409-411.

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Abstract PDF: Giant fibrovascular polyps are very rare benign esophageal lesions arising in the cervical esophagus. We present a case of a 70-year old man with a history of dysphagia. On esophagogram and computed tomogram, a large, sausage-like polyp (7.0 cm in greatest dimension) was identified in the cervical esophagus. Surgical resection of the polyp was successfully performed. Histologically, the polyp was composed of a mixture of highly vascularized fibrous tissue and benign adipose tissue. The fibrous tissue was loosely and densely collagenized and the surface was covered by squamous epithelium. The lesion was diagnosed as a giant fibrovascular polyp and the patient has shown no evidence of recurrence for 8 months after surgery.

Metastatic Medullary Carcinoma of Thyroid to Breast; A Case Initially Diagnosed as Primary Invasive Lobular Carcinoma: A Case Report.: Youngseok Lee, Jungsuk An, Chul Hwan Kim, Bom Woo Yeom, Jong Sang Choi, Yang Seok Chae; Korean J Pathol. 2007;41(6):412-415.

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Abstract PDF: Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance. Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.

Malignant Deciduoid Mesothelioma: A Case Report.: Jung Uee Lee, Bum Kyeong Kim, Yoon Mee Kim, Hae Joung Sul, Kyung Bok Lee, Hoi Young Lee; Korean J Pathol. 2007;41(6):416-419.

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Abstract PDF: Malignant deciduoid mesothelioma is a rare malignant neoplasm occurring in the peritoneum of young women. We report a case of malignant deciduoid mesothelioma that occurred in the omentum of a 47-year-old woman. The patient had never exposed to asbestos and had no history of cesarean section. The lesions were multiple infiltrative nodules affected the peritoneal cavity, omentum, and surface of the uterus with both ovaries. Microscopically, the nodules were composed of mesothelial cells similar to decidual cells

Borderline Clear Cell Adenofibromatous Tumors of the Ovary: Two Case Reports.: Heejeong Lee, Tae Jung Kim, Jeana Kim, Eun Joo Seo, Kyo Young Lee; Korean J Pathol. 2007;41(6):420-423.

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Abstract PDF: Borderline clear cell adenofibromatous tumors are rare with only 26 cases reported in the English literature. Five of these cases exhibited microinvasion and 4 demonstrated intraepithelial carcinoma. We report 2 cases, one typical case and the other with microinvasion. The histological findings revealed widely spaced and focally crowded, variably-sized atypical glands or tubules lined by clear, eosinophilic or hobnail cells set in a dense fibrous stroma. One of the two cases had small solid nests or single cells in the stroma around the proliferative glands less than 1 mm in length that was considered to be a microinvasion.

Solid Variant of Mammary Adenoid Cystic Carcinoma.: Ji Eun Kwon, Yoon Hee Lee, Ju Yeon Pyo, Sang Kyum Kim, Byeong Woo Park, Woo Ick Yang; Korean J Pathol. 2007;41(6):424-426.

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Abstract PDF: Adenoid cystic carcinoma (ACC) is a rare type of breast carcinoma and this tumor makes up less than 0.1% of all mammary carcinomas; ACC is known to show a relatively favorable prognosis. Among a variety of microscopic growth patterns of mammary ACC, a solid variant is the rarest and this can cause diagnostic difficulties. We present here a case of a solid variant of mammary ACC that occurred in the right breast of a 40-year-old woman who was initially diagnosed with invasive ductal carcinoma. We discuss the histological and clinical characteristics of this case.

Pseudometastasis in Sentinel Lymph Nodes with Cytokeratin Debris-containing Histiocytes in Breast Cancer Patient: A Case Report.: Keum Ha Choi, Eun Jung Cha, Ha Na Choi, Woo Sung Moon; Korean J Pathol. 2007;41(6):427-429.

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Abstract PDF: Immunohistochemical staining for cytokeratins can detect false negative nodes in patients with breast carcinoma. We report on a patient with breast carcinoma and pseudometastasis detected by immunohistochemical staining within a negative sentinel lymph node. A 66-year-old woman underwent a simple mastectomy and sentinel lymph node biopsy. Immunohistochemical staining of the sentinel nodes for cytokeratin in permanent sections showed cells with intense cytoplasmic staining in the subcapsular sinus. The cells were negative for epithelial membrane antigen staining, but positive for CD68. In combination with morphologic findings and immunohistochemistry, cytokeratin-positive cells were confirmed as histiocytes with phagocytized cytokeratin debris. Careful correlation with histology and additional IHC could help avoid a misinterpretation of this type of pseudometastasis.

Adrenocortical Carcinoma, Myxoid Variant: A Case Report.: Bomi Kim, Sun Och Yoon, Dong Il Kim, Myung Cherl Kook, Eun Kyung Hong; Korean J Pathol. 2007;41(6):430-435.

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Abstract PDF: Myxoid variant of adrenal cortical carcinoma is extremely rare and there have been only 16 such cases reported in the medical literature. Here we report on a case of 43-year-old woman with a left adrenal mass that was detected during the evaluation for Cushing's syndrome. Left adrenalectomy was performed and the tumor weighed 347 g. The cut surface was predominantly myxoid and gelatinous with central hemorrhage and necrosis. Histologically, the tumor cells were rather small, uniform and polygonal with mild pleomorphism. It showed diverse morphologic patterns according to the amount of the myxoid stromal component. Making the diagnosis was not easy because the tumor was without areas of conventional adrenocortical carcinoma. Immunohistochemically, the tumor cells were positive for alpha-inhibin, synaptophysin and vimentin, but the tumor cells were negative for pan-cytokeratin and CAM 5.2. The immunophenotypes were identical to those of conventional adrenal cortical neoplasms. During the evaluation of a cytokeratin-negative and vimentin-positive retroperitoneal neoplasm with a myxoid component, the possibility of adrenal cortical tumor should be considered in spite that this is a very rare entity.

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