Journal of Pathology and Translational Medicine

Volume 40(4); August 2006

Original Articles

Effects of Selective Cyclooxygenase-2 Inhibitor NS-398 Pretreatment on the Rat Spinal Cord after Contusion Injury.: Hyeon Dae Cheong, Joo Kyung Sung, In Suk Ham, Ku Seong Kang, Joung Ok Kim, Jung Wan Kim, Tae In Park, Yoon Kyung Sohn; Korean J Pathol. 2006;40(4):255-262.

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Abstract PDF: BACKGROUND
Secondary spinal cord injury (SCI) that follows an initial mechanical insult can exacerbate the overall damage, limit the restorative processes and eventually lead to an in- creased neurological deficit. We hypothesized that selective inhibition of cyclooxygenase-2 (COX-2) may decrease the delayed cell death, and so this will contribute to decreased level of the secondary injury.
METHODS
The dorsal surface of the cord at the T9 level was subjected to weight drop impact using a 10 g rod. To block COX-2 activation, a selective COX-2 inhibitor (NS-398) was administered (5 mg/kg, i.p.) 15 min prior to SCI. The COX-1, COX-2, Caspase-3 and PGE2 expressions were measured by real time quantitative RT-PCR and fluorescence immunostaining.
RESULTS
Many activated caspase-3 positive cells were observed at 6 h and they increased until 72 h after SCI. The expression of COX-2 peaked at 6 h after SCI, while the COX-1 expression was unaffected. The principal cells that showed a COX-2 expression were the neurons and microglia. Pretreatment with NS-398 caused a significant decrease in the expression of prostaglandin E2 and activated caspase-3 positive cells after SCI.
CONCLUSION
These data suggest that COX-2 is one of the main factors related with the pathologic deficits from secondary SCI.

Clinicopathologic Analysis of the Micropapillary Variant of Urothelial Carcinoma in Urinary.: Kyungji Lee, Ahwon Lee, Yeong Jin Choi, Kyo Young Lee, Chang Suk Kang, Sang In Shim; Korean J Pathol. 2006;40(4):263-268.

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Abstract PDF: BACKGROUND
Micropapillary urothelial carcinoma of urinary bladder is a rare and aggressive subtype of urothelial carcinoma (UC).
METHODS
AND RESULTS: Seven UCs with a micropapillary component (MPC) were identified by reviewing 135 cystectomy specimens of UC (5.2% in incidence). MPC was associated with conventional UC in 6 cases and the plasmacytoid variant of UC in 1 case. Lymph node metastasis, that characteristically contained MPC was present in 60% (3 out of 5 cases of regional lymph node dissection). Three patients with extensive MPC showed laminar propria invasion (pT1; 33%) and perivesical fat invasion (pT3; 67%). Two out of 3 patients with extensive MPC showed distant metastasis into the colon after cystectomy. The colonic lesions showed exclusively micropapillary differentiation. Four patients with focal or moderate MPC (pT2, 25%; pT3, 75%) were alive without disease at the time of writing this article. All 3 cases with extensive MPC had surface and/or invasive MPC on the prior TURB specimen. Immunohistochemically, the tumor cells were positive for cytokeratin 7, cytokeratin 20, EMA and E-cadherin and tissue retraction spaces that simulate lymphatic spaces were negative for CD34 in all 7 cases.
CONCLUSIONS
This study suggests that the micropapillary growth pattern in UC is a manifestation of aggressive behavior and UC with MPC must be included as part of the differential diagnosis when dealing with a metastatic lesion with a micropaillary structure.

Pathological Findings of Crohn's Disease in the Stomach .: Changyoung Yoo, Bo In Lee, Kyu Yong Choi, Lee So Maeng, Anhi Lee, Chang Suk Kang, Ghee Young Kwon, Kyoung Mee Kim, Cheol Keun Park; Korean J Pathol. 2006;40(4):269-273.

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Abstract PDF: BACKGROUND
The incidence of Crohn's disease in the upper digestive tract, and especially in the stomach, is recently increasing. Focal inflammatory reaction without Helicobacter pylori (H. pylori) infection is thought to be the characteristic pathologic findings suggesting Crohn's disease in the stomach. Yet gastric involvement of Crohn's disease has not been studied in Korea. We studied the endoscopic and pathologic findings of patients with Crohn's disease in the stomach by taking biopsies.
METHODS
Thirty patients with Crohn's disease who underwent gastroduodenoscopy followed by biopsies were included in the study. The pathology of the gastric biopsy specimens and the presence of H. pylori were evaluated.
RESULTS
Among 30 cases, 22 cases (73.3%) were H. pylori negative and 8 cases (26.7%) were H. pylori positive. For the H. pylori negative cases, all but one cases showed pit abscess and focal lymphocytic collections in the antrum. Granulomas were found in 6 cases (20%) and they were exclusively located in the antrum.
CONCLUSIONS
In the stomach, pit abscess and focal lymphocytic collections that are not associated with H. pylori infection are the characteristic pathologic findings found in Crohn's disease.

Alteration of G1/S Cell Cycle Regulatory Proteins in Ovarian Epithelial Tumors.: Jee Yeon Kim, Hwal Woong Kim, Kyung Un Choi, Chang Hun Lee, Mee Young Sol, Hyun Jeong Kang, Dong Hoon Shin; Korean J Pathol. 2006;40(4):274-281.

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Abstract PDF: BACKGROUND
Disturbances of the cell cycle regulatory proteins are key events underlying the development and/or progression of human malignancies. The aim of this study was to evaluate the expression of G1/S cell cycle regulatory proteins in ovarian epithelial tumor.
METHODS
We simultaneously evaluated the expression of cyclin D1, cyclin E, CDK4, CDK2, p16, Rb, E2F1, p53 and the Ki67 labelling index (LI) by immunohistochemical methods in 148 cases of ovarian epithelial tumor of the benign (n=47), borderline (n=29), and malignant type (n=72).
RESULTS
The expression of cyclin E, CDK2, p16, Rb, E2F1, p53 and the Ki67 LI gradually increased from the benign type, through the borderline type, to the malignant tumors. Between the borderline and malignant tumors, the increased expression of cyclin E, E2F1, and p53, and the decreased expression of Rb were significantly associated with malignancy. The reduced Rb expression and the increased E2F1 expression were correlated with the FIGO stage and the histologic grade in the malignant ovarian epithelial tumors. CONCLUSIONS: Cyclin E, E2F1, and p53 overexpressions and the loss of Rb are the important components during carcinogenesis of ovarian epithelial tumors. Our results suggest that in- creased expression of E2F1 should be considered as a new parameter for the prognosis of patients with malignant ovarian epithelial tumors.

Case Reports

ISUP/WHO Classification of Papillary Urothelial Neoplasms of Urinary Bladder: Consensus Study Conducted by Korean Society of Urogenital Pathology.: Jung Weon Shim, Jae Y Ro, Nam Hoon Cho, Young Sik Kim, Yong Wook Park, Sang In Shim, Dong Wha Lee, Yeong Jin Choi, Woon Sup Han; Korean J Pathol. 2006;40(4):282-288.

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Abstract PDF: BACKGROUND
Pathologic grading, one of the most important prognostic factors of papillary urothelial neoplasia (PUN) of the urinary bladder, has been revised continuously. The current study focused on the analysis of interobserver agreement on PUN of the urinary bladder bet- ween 1973 WHO classification (WHO 1973) and 1998 WHO/ISUP classification.
METHODS
Seventy five cases from 15 institutions were collected, and after review by Korean Society of Urogenital Pathology (KSUP), 30 cases were selected as follows; group I, WHO grade 1 and papillary urothelial neoplasm of low malignant potential by ISUP (7 cases), group II, WHO grade 2 and low-grade papillary urothelial carcinoma (16 cases), and group III, WHO grade 3 and high-grade papillary urothelial carcinoma (7 cases). Seventy five general surgical pathologists who participated in this study were asked to grade the tumors based on WHO/ISUP classification. Interobserver agreement between the participants' diagnosis and KSUP consensus diagnosis was analyzed by kappa value.
RESULTS
Interobserver agreement assessed by kappa value for all diagnostic groups was very low; for group I, kappa value was -0.900893722; for group II, -0.944650025, and for group III, -0.876728996. The overall kappa value of pathology residents was better than that of practicing pathologists.
CONCLUSIONS
The 1998 WHO/ ISUP classification could not be easily translated from the 1973 WHO classification and because of poor interobserver agreement, it appears that further work would be needed before it can be practically applied.

Propylthiouracil-induced Hepatic Injury: A Case Report.: Ji Eun Kwak, Han Seong Kim, Sun Hee Chang, Mee Joo, Je G Chi, Jin Soo Moon, Jong Guk Lee; Korean J Pathol. 2006;40(4):289-291.

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Abstract PDF: Propylthiouracil (PTU) is one of the most widely used drugs for the treatment of the hyperthyroidism. However the liver damage is a rare adverse effect, which can be fatal. We present a case of PTU-induced hepatitis. A 13-year-old girl was diagnosed as having Graves' disease, for which PTU was administered. Three months after commencing PTU, she developed jaundice accompanied with elevated serum transaminases and total bilirubin levels. The viral markers were all negative. The pathologic findings of the liver biopsy included necrosis of hepatocytes predominantly around the central veins (i.e., zone 3 necrosis) and moderate to severe infiltration of lymphocytes in portal areas. After withdrawal of the PTU, clinical symptoms and liver function test results were improved gradually.

Ectopic Hamartomatous Thymoma: A Case Report along with a Review of the Literature Concerning the Histogenesis and New Nomenclature.: Sang Hee Seok, Dong Hyun Lee, Su Hwan Kang, Young Kyung Bae; Korean J Pathol. 2006;40(4):292-296.

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Abstract PDF: Ectopic hamartomatous thymoma (EHT) is a rare and distinctive benign neoplasm of the lower neck. We here report on a case of EHT arising in the suprasternal area of 47-year-old male patient. The well-circumscribed mass measured 7 x 6 x 4 cm and it predominantly had a solid gray-white cut surface. Microscopically, the tumor consisted of spindle cells, epithelial nests, and mature adipose tissue. The epithelial component was arranged in anastomosing cords, solid nests and variable-sized cysts that were lined by squamous or cuboidal epithelium. The spindle cells revealed the myoepithelial immunohistochemical phenotype. There was no obvious thymic differentiation nor was any normal thymic tissue observed in our case. We think that EHT needs to be reclassified with using different nomenclature to designate its origin and histology. Further, pathologists and clinicians should be aware of the existence of this tumor in the lower neck so as not to mistake it for high-grade sarcoma or spindle cell carcinoma.

Ameloblastoma Associated with Dentinogenic Ghost Cell Tumor: A Case Report.: Tae Jung Kim, Youn Soo Lee, Byung Kee Kim, Kyo Young Lee; Korean J Pathol. 2006;40(4):297-302.

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Abstract PDF: Dentinogenic ghost cell tumor (DGCT) is an uncommon odontogenic tumor. It is characterized by islands of odontogenic epithelial cells that contain numerous ghost cells and dysplastic dentin. Occasionally, DGCT combines with other odontogenic tumors, such as ameloblastoma. We report here on a 21-year-old female who complained of a tender solid mass in the left maxilla for the 7 month previous to her admission. MRI revealed a relatively well demarcated mass in the left maxilla with heterogenous signal intensity, measuring 3.2 x 2.8 cm, and this mass had invaded the left palate. Microscopically, the tumor was composed of nests of odontogenic epithelium that contained ghost cells and calcification with dysplastic dentin, which is all consistent with DGCT. Localized area showed odontogenic epithelial follicles that had peripheral palisading and satellite reticulum without ghost cells and dentin, and this is consistent with ame- loblastoma. The immunohistochemistry revealed cytokeratins, EMA, S100 and Bcl-2 positivity in areas of the DGCT and ameloblastoma. In the ameloblastoma, Bcl-2 positivity was noted in the palisading basal cells. We concluded that the tumor was an ameloblastoma associated with DGCT.

A Case of Combined Hepatocellular Carcinoma-Cholangiocarcinoma with Pseudosarcomatous Features.: Ok Ran Shin, Jae Young Park, Hae Kyung Lee, Young Jin Choi, Kee Hwan Kim, Young Mi Ku, Keun Woo Lim; Korean J Pathol. 2006;40(4):303-305.

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Abstract PDF: Combine hepatocellular-cholangiocarcinoma with pseudosarcomatous features is a rare primary liver tumor. We report a 46-year-old man who is a carrier of HBV and has presented intermittent severe abdominal pain on right upper quadrant for 6 days. Tumor markers, alpha-fetoprotein, CEA and CA19-9 were within normal ranges. Abdominal computed tomogram revealed a large heterogeneous mass in the posteroinferior segment of right liver without associated biliary dilatation and conglomerated, enlarged portocaval and peripancreatic lymph nodes. Right hepatectomy was performed with local lymph node dissection. The tumor, measuring 7.5 x 5.5 cm showed an ill demarcated round to oval shape and a variegated whitish yellow solid cut surface with necrosis. Microscopically, the tumor consisted of three components, hepatocellular carcinoma, cholangiocarcinoma and undifferentiated sarcomatoid tumor cells. Immunohistochemically, hepatocellular carcinoma portion reacted positively with alpha-fetoprotein, cholangiocarcinoma portion reacted positively with bile duct-type cytokeratins (cytokeratin 7 and 19) and EMA. The pseudosarcomatous portion reacted with bile duct type cytokeratins and EMA. These findings suggested that pseudosarcomatous tumor cells may be with closely, associated primitive stem cells that can differentiate into the ductal epithelium.

Sarcomatoid Carcinoma of the Pancreas: A Case Report.: Kyung Hee Kim, Dae Young Kang, Min Koo Lee, Hyeon Woong Yang, Hyun Young Han; Korean J Pathol. 2006;40(4):306-310.

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Abstract PDF: We report here on an unusual case of a 73-year-old Korean female with sarcomatoid carcinoma. This tumor was composed of pancreatic ductal adenocarcinoma and a malignant fibrous histiocytoma-like stroma. The CT imaging revealed a multiseptated heterogenous hypodense mass that was 15 cm in size. The mass was located in the body and tail of the pancreas, spleen and gastrosplenic area. The pathologic examination showed that the carcinomatous component was negative for vimentin, and the sarcomatous component was positive for vimentin and CD 68. The ultrastructural examination showed that both the carcinomatous and sarcomatous components had desmosomes at the cell-cell contact sites. The patient refused postoperative adjuvant chemotherapy and she died of cachexia with generalized tumor extension about 3 months later. This report presents special data that can clarify the clinicopathological features and pathogenesis of this rare neoplasm.

Well Differentiated Papillary Mesothelioma of the Ovarian Surface: A Case Report.: Hwa Eun Oh, Ji Sun Song, Ki Young Ryu, Sun Lee; Korean J Pathol. 2006;40(4):311-313.

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Abstract PDF: Well differentiated papillary mesothelioma (WDPM) is an unusual variant of epithelial mesothelioma. Most WDPMs exhibit either benign or indolent behavior. Making the differential diagnosis between this rare tumor and serous papillary carcinoma can be problematic. We report here on a case of a 43-year-old woman with a WDPM of the surface. She presented to our hospital for a routine gynecologic evaluation, and she had no specific symptoms or a history of asbestos exposure. Gynecologic ultrasonography revealed a right ovarian mass that measured 6 x 3.8 x 3 cm in size. No ascites was detected. Right salpingo-oophorectomy was performed; grossly, the tumor was a yellowish firm, multinodular mass. Microscopically, the tumor consisted of numerous papillae that were lined by a single layer of uniform mesothelial cells. Nuclear pleomorphism and mitoses were not found. On immunohistochemical study, the tumor cells were positive for calretinin and cytokeratin, but they were negative for CEA. It is important to differentiate WDPM from serous papillary carcinoma or other malignant tumors to avoid treating them as malignant tumors.

Osteosarcoma of the Skull Resembling Desmoplastic Fibroma: A Case Report.: Ingu Do, Eui Jong Kim, Gook Ki Kim, Yong Koo Park; Korean J Pathol. 2006;40(4):314-317.

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Abstract PDF: Primary osteosarcoma of the skull is a rare finding. We report here on a pathologically proven case of osteosarcoma that presented as a painless mass in the frontal bone of a 7-year-old boy. This unusual form of osteosarcoma had features of desmoplastic fibroma in a large portion of the tumor. We also include a review of the medical literature related to osteosarcoma.

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