Journal of Pathology and Translational Medicine

Volume 30(8); August 1996

Original Articles

Application of the Revised Case Matrix Format to Tutorial in Pathology Teaching: An Interim Approach toward Problem-Based Learning under Traditional Curricular Structure.: Yong Il Kim, Chong Jai Kim, Gee Young Kim, Chul Woo Kim, Woo Ho Kim, Ja June Jang, Je Geun Chi, Gyeong Hoon Kang, Myeong Cherl Kook, Jung Sun Kim, Tae Sook Kim, Gee Young Kwon, So Dug Lim; Korean J Pathol. 1996;30(8):570-661.

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Abstract: This paper describes a student-centered case study program concerning the tumor pathology course for first year students in medical school under the traditional curricular structure. A traditional, discipline-oriented, lecture-laboratory approach was partly modified by introducing a tutuorial session using a modified case matrix format during the laboratory hours without altering the general scheme of the existing system. Small group tutorial sessions were set with the development of learning objectives emphasizing clinicopathologic reasoning and early exposure to future practical presentation which was followed by the large class session; each tutorial was supplied with a short clinical history, gross kodachrome slides, and microslides. The session for problem identification was replaced by proving a series of instructor-designed questions for both pathology and interdisciplinary correlation during which pedagogical implication was stressed the most. Student's active participation, development of self learning skill and vigorous teaching-learning process among students, and motivation/relevance for forthcoming pathology study were among the benefits conferred by this modification. We conclude that this approach is an interim step to meet the advantages of problem-based learning even in a traditional curricular structure.

Expression of p53, bcl-2 Proteins and Estrogen Receptors in Human Breast Cancer.: Hee Kyung Chang, Choong Han Lee, Man Ha Huh; Korean J Pathol. 1996;30(8):662-670.

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Abstract PDF: In 56 breast cancer tissues (infiltrating ductal carcinoma) with a clinical follow-up period of more than 5 years, positivity of estrogen receptor(ER) by enzyme immunoassay and expressions of bcl-2 and p53 oncoproteins by immunohistochemistry were evaluated. The purposes of this study were to determine prevalence of bcl-2 and p53 in breast cancer, the interrelationship between expression of the proteins and estrogen receptor, correlation between histologic grade and the expression of the tumor-related oncogenes, and to explore the biologic bahavior of breast cancer (lymph node metastasis, recurrence rate, and survival) via expression of bcl-2 and p53. Twelve of 56 (21.4%) carcinomas were bcl-2 positive, and seventeen (30.4%) were p53- positive. Eleven of 12 bcl-2 positive tumors (91.7%) were ER-positive, and bcl-2 expression was significantly associated with ER-positivity(P=0.043). Seven of 36 ER-positive tumors (12.5%) were p53 positive, and p53 expression was inversely associated with ER-positivity(P=0.006) significantly. The bcl-2 protein expression showed a significant relationship to low histologic grade of tumor (P=0.0002), and an almost significant relationship to lower recurrence rate (P=0.09). The p53 protein expression showed a significant relationship to high histologic grade of tumor (P=0.002) and an almost significant relationship to lymph node metastasis (P=0.09). Also an almost inverse relationship between bcl-2 and p53 was demonstrated (P=0.057). The bcl-2 expression had a tendency to be associated with longer patient survival(P= 0.09), but p53 immunoreaction was found not to be associated with shorter patient survival(P=0.16). These results provide further evidence that higher incidence of bcl-2 expression is correlated with higher incidence of ER and lower grade of tumor, while p53 expression is correlated with lower incidence of ER and higher grade of tumor. In conclusion, although the biologic function of bcl-2 protein is not yet well understood in breast cancer, our results suggest that bcl-2 and p53 oncoproteins might play significant roles in estrogen receptor and development of breast cancer. But their prognostic significance could not be determined; our results are 'not significant' but 'almost significant'. Thus, contribution of bcl-2 and p53 immunohistochemical phenotyping of breast cancer with ER to the clinical management need verification in larger series.

A Study on the Tumor Angiogenesis and Expression of Cytokine and Growth Factors in the Prostatic Carcinoma.: Sung Chul Lim, Ho Jong Jeon; Korean J Pathol. 1996;30(8):671-679.

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Abstract PDF: There is considerable experimental evidence to indicate that tumor growth is dependent on angiogenesis. However, we do not understand how the angiogenic activity is initiated by a given tumor. There is a clear distinction between a stage without neovascularization, which correlates with a paucity of metastases, and a stage in which increasing neovascularization correlates with a rising rate of metastasis. The authors therefore asked whether the extent of angiogenesis in human prostatic carcinoma is correlated with the tumor grades or some growth factors. To investigate how tumor angiogenesis correlates with tumor aggressiveness, the authors counted microvessels within the various grades of invasive prostatic carcinomas of 44 patients and the nodular hyperplasias of 10 patients. Highlighting of the vessels by immunohistochemical staining for factor VIII-related antigen and assessment of the tumor aggressiveness by the degree of expression of some growth factors(transforming growth factor-alpha, and beta, epidermal growth factor), tumor necrosis factor-alpha and tumor grading(Gleason's score) were done. As a result, both microvessel counts and the expression of growth factors and tumor necrosis factor correlated with tumor grades. In conclusion, the number of microvessels per 200 X fields in the areas of most intense neovascularization in a prostatic carcinoma may be a predictor of the patient's prognosis. Therefore, assessment of tumor angiogenesis may prove valuable in selecting patients with prostatic carcinoma, especially small needle biopsy, for aggressive therapy.

Effects of Progesterone Treatment on the Squamous or Morular Metaplasia Associated with Endometrial Hyperplasia.: Kyu Rae Kim, Hee Jeong Ahn; Korean J Pathol. 1996;30(8):680-686.

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Abstract PDF: During evaluation of follow-up curettage of endometrial hyperplasia after progesterone treatment, we have noticed that the foci of squamous or morular metaplasia are persistent or even markedly increased after the hyperplastic glands have all disappeared. These observations have led us to study the histological changes of squamous or morular metaplasia in the hyperplastic endometrium after progesterone treatment and to examine the changes of estrogen receptors(ER) and progesterone receptors(PR) to find out, if there is any pathogenetic role of progesterone administration on the squamous or morular metaplasia. Squamous or morular metaplasia was associated in 21 cases (13.5 %) out of 156 endometrial hyperplasia during the study periods and all of them were associated with complex hyperplasia, but not associated with simple hyperplasia. At follow-up curettage after progesterone treatment, squamous metaplasia newly appeared in 3 cases(20 %), markedly increased in 4 cases(26.7%), persisted in 4 cases(26.7%) and decreased in 4 cases(26.7%), even after hyperplastic glands have all disappeared or were markedly decreased. On immunohistochemical staining, metaplastic foci showed ER- and PR- in 13 cases (87 %) in contrast to the surrounding endometrium and the remaining 2 cases showed minimal ER+ and PR+ confined to several nuclei. Intensity or staining pattern of ER and PR in metaplastic foci were not changed with progesterone treatment. In the background endometrium, intensity of glandular ER+ and PR + was higher than that of the stroma at the initial curettage, however, progesterone treatment predominantly down-regulated glandular ER+ more than stromal ER+. Increment or persistence of squamous metaplasia along the progesterone treatment seemingly would implicate hormonal influences as playing a significant role in the formation of squamous or morular metaplasia and the absence of cellular receptors for these hormones in the metaplastic foci may suggest qualitative changes in the receptors.

Ultrastructural In Situ Hybridization Method for Detection of Oncogenic Viruses.: Keun Hong Kee, Chul Hee Choi, Ho Jong Jeon; Korean J Pathol. 1996;30(8):687-698.

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Abstract PDF: In situ hybridization (ISH) is a standard method for localizing DNA or RNA sequences in tissue or cell preperation. The technique was developed at the electron-microscopic level, and enables the precise subcellular localization. A method was developed for detection of specific viral DNA. We have tested various methods and technique to detect specific viral DNA through ISH at the electron microscopic level. Postembedding method of ultrastructural ISH was developed and successfully applied for the detection of human papillomavirus type 16 in squamous cell carcinoma of the uterine cervix and Epstein-Barr virus in EBV-infected leukemia cell line. The following results are made. The best results were obtained using 0.2% glutaraldehyde and 4% paraformaldehyde fixed tissue or cell block. The labelling was best observed on Unicryl resin and Lowicryl K4M resin sections. Epon sections showed no reactivity. Thin sections of Unicryl resin were more easier than Lowicryl K4M resin. Enzymatic predigestion with proteinase K, pepsin and trypsind gave good results. However, high concentration of these produce poor results due to excessive destruction of the cellular components. Alkali treatment with 0.5N sodium hydroxide produced successful results in denaturation of target DNA. The labelling density of gold particles was independent of incubation time or temperature in hybridization step. The viral DNA labelling was localized mainly within the nucleus, both within and at the edge of electron dense regions, and below the nuclear membrane. And the labelling was seen in the form of a dense, roughly spherical shape. In conclusion, the best results are obtained by the conditions that tissue fixed by 0.2% glutaraldehyde and 4% paraformaldehyde solution, embedded with Unicryl resin, protein denaturation by 0.1ul/ml proteinase K, DNA denaturation by 0.5N sodium hydroxide, and reaction with DNA probe.

EBV in Situ Hybridization Study for Cutaneous T-Cell Lymphomas.: Chan Kum Park, Chang Woo Lee, Jung Dal Lee; Korean J Pathol. 1996;30(8):699-705.

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Abstract PDF: We studied 24 cases of cutaneous T-cell lymphomas and six cases of benign lymphoproliferative diseases of the skin (2 Jessner's lymphocytic infiltration, 2 pseudolymphoma, 2 lymphomatoid papulosis) for the presence of Epstein-Barr Virus(EBV) RNA, using the in situ hybridization(ISH) method. Among the 24 cases of cutaneous T-cell lymphomas (CTCL), 18 cases including 12 cases of mycosis fungoides(MF) were primary CTCL, and the other 6 cases were secondary CTCL. The ISH study demonstrated a positive reaction for EBER probe in 6 out of the 24 cases(25%) of CTCL, and a negative reaction for BHLF nuclear RNA probe in all the cases studied. Double-labelling immunohistochemistry/ISH studies revealed that the EBV positive cells were CD45RO positive and CD20 negative. EBV genome was not demonstrated in any benign lymphoproliferative diseases of the skin. Among the EBER positive cases, none of the 12 cases of MF demonstrated EBER signals, and 6 out of the 12(50%) cases of CTCL were positive for EBER probe. In conclusion, latent infection of EBV may play a role in the development of non-mycosis fungoides T-cell lymphomas involving the skin.

Case Reports

Malignant Rhabdoid Tumor of the Kidney: A report of two cases: An immunohistochemical and ultrastructural study.: Seung Sam Paik, Moon Hyang Park; Korean J Pathol. 1996;30(8):706-714.

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Abstract PDF: Malignant rhabdoid tumor of the kidney(MRTK), an uncommon renal tumor found in children, is one of the most lethal neoplasms of early life. It was first recognized during a review of the first National Wilms' Tumor Study(NWTS) as an extremely aggressive neoplasm whose appearance often mimicks those of skeletal muscle tumors, but without histological, immunohistochemical, and ultrastructural markers of rhabdomyogenesis. Herein we present two cases of malignant rhabdoid tumor of the kidney, one occurring in a 6-month-old male baby, and the other in a 123-month-old girl. They presented a huge tender mass on the left upper quadrant of the abdomen. Microscopically, each case was very cellular and composed of sheets of round or polygonal cells with ample cytoplasm often containing eosinophilic filamentous inclusions and round vesicular nuclei with prominent nucleoli. Case 1 showed lymphomatoid pattern, but case 2 showed foci of several variant patterns associated with classic appearances. The tumor cells showed a strong reactivity for vimentin in both cases. Unusually, case 2 showed focal reactivity for epithelial membrane antigen(EMA), muscle specific actin, and smooth muscle actin. Ultrastructural study confirmed the presence of whorled bundles of intermediate filaments in paranuclear position, and a prominent nucleolus.

Ureteral Fibroepithelial Polyp: A report of four cases (One case with nephrogenic adenoma).: Won Mee Lee, Seung Sam Paik, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1996;30(8):715-720.

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Abstract PDF: Fibroepithelial polyps of the ureter are usually acquired rather than congenital. Most polyps are hamartomatous growths which tend to arise in the proximal portion of the left ureter. Most patients exibit either hematuria or persistent flank pain secondary to partial ureteral obstruction. Because of false positivity of urine cytology, as well as intravenous pyelogram, the correct diagnosis is confused with malignancy. Herein we report four cases of ureteral fibroepithelial polyp, which are associated with stones resulting in partial obstruction of the ureter. One of the four cases is associated with nephrogenic adenoma in the lamina propria of the adjacent ureter. The following report describes clinicopathologic findings of fibroepithelial polyp with review of literatures.

Syphilitic Granulomatous Pancreatitis: A case report.: Seong Eun Yang, Yoon Ju Kim, Sung Suk Paeng, Duck Hwan Kim, Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1996;30(8):721-725.

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Abstract PDF: Syphilitic granulomatous pancreatitis is an extremely rare condition,and can occur in the generalized acquired syphilitic patient in tertiary or secondary phase. The most serious problem with granulomatous pancreatic lesion is clinical or radiological misdiagnosis as cancer. We experienced a case of syphilitic granulomatous pancreatitis arising in 54 year old female patient. She was treated for syphilis 20years ago. But she and her husband are still strong positive to VDRL and TPHA. On abdominal computed tomography and endoscopic pancreatico- duodenography, there was an obstructive mass of low density in the distal common bile duct or pancreatic head. Under the preoperative diagnosis of pancreatic head carcinoma, Whipple's operation was done. On gross examination, the pancreas was fibrotic, and the common bile duct was well preserved without tumor mass. Microscopically, numerous intralobular noncaseating epithelioid cell granulomas with multinucleated giant cells are identified. They surround thick-walled, small to medium sized arteries and involve vascular wall with luminal narrowing or obliteration, which are characteristic findings of the syphilitic granuloma. The remaining parenchyme shows fibrosis, acinar atrophy or destruction with dense infiltration of lymphohistiocytes, plasma cells with granuloma formation. Although the Warthin-Starry stain reveals no spirochetes, the serologic result and pathologic findings are compatible with syphilitic granulomatous pancreatitis.

Intraductal Papillary-Mucinous Neoplasm of the Pancreas: A case report.: Ji Eun Kim, Young Hyeh Ko, Howe Jung Ree, Yong Il Kim, Poong Ryul Lee; Korean J Pathol. 1996;30(8):726-732.

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Abstract PDF: Intraductal papillary mucinous neoplasm (IPMN) is a recently recognized clinicopathologic entity characterized by dilatation of pancreatic duct filled with copious mucin and papillary ductal epithelial proliferation ranging from simple hyperplasia to invasive carcinoma. The exact clinicopathologic identification of this tumor is important because of favorable prognosis contrast to that of conventional ductal adenocarcinoma. Herein we report a case of surgically resected typical IPMN. A 59-year-old man had a long history of diabetes mellitus with epigastric pain of 4 months duration. Ultrasonography and computed tomographic examination revealed cystic dilatations of main pancreatic duct in the head. The patient underwent total pancreatectomy. The gross appearance showed diffuse dilatation of main pancreatic duct associated with cystic dilatation of subbranches in the uncinate process. Histologic examination revealed diffuse papillary proliferations lined by mucinous epithelium with mild atypism within ectatic ducts. No invasive carcinoma was noted. Histochemically, the papillary epithelium contained mostly neutral and acid sialomucin.

Bizarre Parosteal Osteochondromatous Proliferation: A report of five cases.: Bohng Hee Kim, Yong Koo Park, Youn Wha Kim, Moon Ho Yang; Korean J Pathol. 1996;30(8):733-738.

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Abstract PDF: Bizarre parosteal osteochondromatous proliferation was first described in 1983, when Nora and his collegues reported 35 examples of a proliferative lesion involving bones of the hands and the feet. In 1993, Meneses reported 65 cases of this condition. A fourth of all the reported cases involved the long bones. It is important to identify the clinical, roentgenographic, and histologic characteristic to seperate it from other entities because it is a benign lesion with atypical microscopic features with a tendency to recur. Roentgenograms show a calcific mass attached to the underlying cortex having a broad base. Histologically, the lesion exhibites proliferative activity, irregular bony cartilaginous interfaces, and enlarged, bizarre, and binucleated chondrocytes. We reviewed the bone tumors, diagnosed in the KyungHee University Hospital, dated from 1984 to 1994. Five cases were revised to Nora's lesion, all of which were previously diagnosed as osteochondroma. The ages of the patients ranged from 12 to 57 years (median, 19 years), and all of them were males. Two cases involved the bones of hands and feet (metacarpal and talus), and 3 cases involved the long bones (humerus, fibula, and ulna). One lesion involving the humerus has a recurrence. No metastasis had been reported.

Adenoid Basal Carcinoma Associated with Invasive Squamous Cell Carcinoma of Uterine Cervix: A case report.: Hyun Jung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee; Korean J Pathol. 1996;30(8):739-741.

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Abstract PDF: Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions. Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.

Endothelial Cyst of the Adrenal Gland: Report of a case.: Sung Chul Lim, Mi Sook Lee, Yun Sin Kim, Keun Hong Kee, Yu Kyung Jeong, Mi Ja Lee, Soon Bong Chung; Korean J Pathol. 1996;30(8):742-745.

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Abstract PDF: Adrenal cysts are rare lesion that usually present themselves as an incidental finding during surgery, or at the time of autopsy. The cysts are usually small, seldom exceeding 10cm in diameter, and are generally asymptomatic. However, they present a difficult problem in differentiation between benign and malignant lesions of the adrenal gland. In the differential diagnosis, other cystic lesions of the upper abdomen must also be considered, including hepatic, splenic, renal and pancreatic cysts. Herein we report a case of endothelial cyst of lymphangiomatous type of the adrenal gland which was detected in a 44-year-old male patient during a routine health examination by ultrasonography as a pancreatic pseudocyst. Gross examination revealed multiple separate but continuous cysts, measuring 10.6x8x7cm in dimension. Within the wall, compressed adrenal cortex was noted. Microscopically, fibrous wall containing hypertrophied smooth muscle lined by endothelial cells was also noted. We reviewed literatures of the adrenal cyst and report a case.

Lipoma of the Heart: An Autopsy case report.: Min Hee Jung, Suk Hee Lee, Sang Han Lee, Jong Min Chae, Jung Sik Kwak; Korean J Pathol. 1996;30(8):746-748.

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Abstract PDF: Lipomas of the heart are benign neoplasms and have rarely been described. Due to the fact that they normally cause no symptoms, diagnosis is often purely accidental. Because of the rarity of these tumors, it seems worthwhile to present an example studied at autopsy. It was associated with the sudden death of a 15-year-old boy. The tumor arose from the wall of the left ventricle and occupied the pericardial cavity, measuring 13x7x6 cm in size. The tumor was whitish-yellow, translucent, and soft. Microscopically, the tumor was composed of mature adipose tissue which extended between muscle fibers. This current case, the giant cardiac lipoma is believed to produce disturbances of the conduction system and distrubances of cardiac filling.

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