Journal of Pathology and Translational Medicine

Volume 30(9); September 1996

Original Articles

Expression Pattern of Tumor Progression and Metastasis-related Gene Proteins - CD44H, CD44v6, erbB-2, and p53 -in Gastric Carcinoma.: Sung Woo Joo, Young Jhoon Chin, Dae Cheol Kim, Gi Yeoung Huh, Sook Hee Hong; Korean J Pathol. 1996;30(9):751-763.

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Abstract PDF: Immunohistochemical studies of the molecules associated with gastric tumor progression and metastasis were done to evaluate their relationship with known prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The 4 antibodies used in this study were CD44H, CD44v6, erbB-2, and p53. The CD44H expression was detected in 76 (59.8%), CD44v6 in 63 (49.6%), erbB-2 in 18 (14.2%), and mutant p53 in 98 (77.2%) out of 127 cases of gastric carcinomas. There was no significant correlation between the expression rates of each four proteins. The expression rates of all 4 proteins were not significantly correlated with age and sex of the patients and lymph node metastasis, but the correlation between CD44v6 expression and the depth of tumor invasion and tumor stage was significant (p<0.05). These results suggest that CD44v6 is closely associated with tumor invasion, and high levels of CD44H, erbB-2 and p53 are associated with tumorigenesis of the stomach as they are highly expressed in early as well as in advanced gastric carcinomas. The findings also support the conclusion that the loss of control of alternative CD44 mRNA splicing resulted in production of CD44v6 splicing variant in tumor cell facilitates tissue invasion by increased adherence of the tumor cell to an extracellular matrix or by tumor cell migration. It can be expected that CD44v6 overexpression in tumor cells appears to be an important prognostic indicator for gastric tumor progression.

Histopathologic Analysis of Helicobacter Pylori Associated Gastritis.: Ho Jung Lee, Eun Sil Yu, In Chul Lee; Korean J Pathol. 1996;30(9):764-774.

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Abstract PDF: Gastric mucosa shows continuous changes in surface epithelium as well as inflammatory reaction by various substances from the outside and their metabolic products. Gastric mucosal lesions are proven to be associated with bacterial infection by the discovery of Heliobacter pylori(H. pylori) and many studies about histopathologic changes of gastric mucosa associated H. pylori infection has been advanced. It is known that H. pylori associated gastritis displays surface foveolar epithelial changes, such as cytoplasmic vacuolation, mucin loss, juxtaluminal cytoplasm erosion, epithelial denudation, and mucosal irregularity. There have been many studies that H. pylori infection is associated with intestinal metaplasia, gastric dysplasia, and carcinoma. Also chronic H. pylori infection with its induction of gastric lymphoid follicle has been implicated as a precursor of gastric lymphoma of the unique B-cell type that arises from mucosa-associated lymphoid tissue(MALT). However, these gastric mucosal changes are also observed in gastritis with other causes. In this study, we aimed to define specific histopathiologic findings associated with H. pylori infection. A total of 463 gastric biopsy specimens were reviewed. They were Helicobacter-associated gastritis and were divided as many (MH), a few (AH), and no (NH), according to the number of H. pylori. 210 (MH), 131 (AH), and 122 (NH) biopsy specimens were included. Lymphocytes, plasma cells in lamina propria, eosinophils and neutrophils in surface epithelium and crypt as well as lamina propria were graded from 0 to 3. Surface epithelial changes including cytoplasmic vacuolation, mucin loss, juxtaluminal erosion, epithelial denudation and mucosal irregrarity were observed in 200 of 210 cases(95%) in MH group, 34 of 131 cases(26%) in AH group, and 6 of 122 cases(5%) in NH group. This result indicates there is significant difference in surface epithelial changes according to the number of H. pylori(p<0.001). Severity of eosinophil, neutrophil, lymphocyte, and plasma cell infiltration is increased in proportion to the number of H. pylori. Especially, neutrophilic infiltration is not identified in 95 of 122 cases(78%) in NH group, whereas MH group shows severe infitration (grade 3) in 127 of 210 cases(61%), and no (grade 0) in 11 of 210 cases(5%). This data well explains that the severity of neutrophil infiltration is associated with, the degree of H. pylori infection in chronic active gastritis, with statistical significance. The prevalence of lymphoid follicle formation was 17 of 120 cases(14%) in NH group, 24 of 131 cases(18%) in AH group, and 52 of 210 cases(25%) in MH group. This shows that lymphoid follicle formation correlates with the number of H. pylori, but without statistical significance. The prevalence of intestinal metaplasia in NH, AH, and MH was 43 of 122 cases(35%), 46 of 131 cases(35%), and 69 of 210 cases(33%), showing no association between intestinal metaplasia and H. pylori. In summary, H. pylori associated gastritis dispays characteristic histopathological changes in gastric mucosa, in which surface epithelial changes and various inflammatory infiltrates are increased in proportion to the number of H. pylori. Especially vacuolization of surface foveolar epithelium, cryptitis, and crypt abscess are specific findings of H. pylori associated gastritis.

The Study of p53 Expression and DNA Ploidy in Colorectal Carcinoma.: Ji Shin Lee, Kwang Soo Cheon, Chang Soo Park; Korean J Pathol. 1996;30(9):775-783.

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Abstract PDF: Mutation of the p53 gene frequently results in overexpression of the p53 protein and loss of its tumor-suppressing properties. The overexpression of the p53 gene could be an indicator of rapid proliferation, poor differentiation, advanced stages, or poor prognosis. The prognostic value of the overexpression of the p53 gene in colorectal carcinoma is equivocal. The presence of DNA aneuploidy has been described as a powerful adverse prognostic indicator in relation to survival. To investigate the prognostic significance of p53 expression, and the relationship with DNA ploidy, 92 cases of colorectal carcinomas were analyzed. The overexpression of p53 gene product was present in 50(54.4%) of 92 cases. p53 expression only correlated with recurrence or metastasis during the follow-up periods (p=0.045). DNA aneuploidy was observed in 32(39.1%) of 82 cases. DNA ploidy was strongly associated with lymph node invasion(p=0.005), Dukes' stage(p=0.003), TNM classification (p=0.003), and recurrence or metastasis during the follow-up periods (p=0.045). The frequency of DNA aneuploidy was higher in the p53-positive colorectal carcinomas(58.3%) than in the p53-negative colorectal carcinomas (21.6%) (p=0.003). p53-positive colorectal carcinomas had a higher rate of cell proliferation than p53-negative cases(p<0.001). These results suggest that checking the p53 expression and DNA ploidy could be useful prognostic indicators of colorectal carcinoma.

Correlation between Histopathologic Grade, Stage, and Degree of EGFR Expression in Transitional Cell Carcinoma of the Urinary Bladder.: Hyeon Ok Kim, Hwa Sun Lee, Kang Suek Suh; Korean J Pathol. 1996;30(9):784-791.

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Abstract PDF: This study was performed to estimate the correlation between the histopathological grade and the clinical stage, which are known as important prognostic factors, and EGFR expression status in 57 cases of transitional cell carcinoma of the urinary bladder. There was a significant correlation between the histopathological grade and clinical stage of transitional cell carcinoma of the urinary bladder and between expression grades of EGFR and histopathological grades, or clinical stages of transitional cell carcinoma of the urinary bladder. Therefore, the presence of a high intensity of EGFR staining in the transitional cell carcinoma of the urinary bladder was associated with poor differentiation and invasion. On the basis of the above results, it was suggested that the degree of EGFR expression is one of the objective and reliable prognostic factors in transitional cell carcinoma of the urinary bladder.

Establishment and Characterization of an Epstein-Barr Virus-negative B-cell Line from a Patient with Dissemination of Peripheral Blood and Bone Marrow by Malignant Lymphoid Cell.: Ho Jong Jeon, Mi Ja Lee, Yu Kyung Jeong, Yoo Hwan Park, Choon Hae Chung, Yoon Kyung Oh, Chul Heel Choi, Sang Woo Cheong; Korean J Pathol. 1996;30(9):792-809.

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Abstract PDF: A human malignant lymphoid cell line(JeKo-1) was established from a Korean patient with retroperitoneal tumor presenting peripheral blood and bone marrow involvement by malignant lymphoid cells. This cell line was established from peripheral blood, and the cell line had the identical immunophenotypic features as malignant cells from the peripheral blood. The established cell line had features of a mature B-cell phenotype with no evidence for commitment to other lineages. The JeKo-1 grows in suspension with a doubling time of 33 hours. By light and electron microscopic examination, the established cells had a follicular center showing, a small, cleaved, lymphoid appearance, and had a large amount of cytoplasm containing few vacuoles and an irregular cytoplasmic membrane. Immunophenotypic analyses with monoclonal antibodies using flow cytometry showed a monoclonal IgM kappa and CD5- B-cell phenotype. The cells were non-reactive for T-cells and myeloid/monocyte antigens, and no evidence of Epstein-Barr virus nuclear antigen by polymerase chain reaction. DNA analysis showed a hypodiploid stemline with a DNA index of 0.83. The established cells were strongly reactive for bcl-2 and c-myc onco-protein, but lacked expression of multidrug resistance gene protein, p-glycoprotein by Western blot analysis. Karyotypic analysis of JeKo-1 showed 40-41 chromosomes. This cell line should be a valuable tool to study the dissemination of malignant lymphoma into the peripheral blood and bone marrow.

Expression of bcl-2 and c-myc Proteins in Epidermal and Melanocytic Tumors.: Young Ha Oh, Chan Kum Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):810-818.

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Abstract PDF: bcl-2 and c-myc protein expression were studied in 44 epidermal (8 seborrheic keratoses, 21 squamous cell carcinomas, and 15 basal cell carcinomas), and 26 melanocytic tumors(8 nevi, and malignant melanomas) by immunohistochemistry using the specific anti-bcl-2 and anti-c-myc monoclonal antibodies. 14 out of 15 basal cell carcinomas(BCC) (93.3%) showed expression of bcl-2 protein, 12 of which (85.7%) showed coexpression of c-myc protein. In the melanocytic tumors, 7 out of 8 nevi showed bcl-2 expression (87.5%). Five of these 7 cases (62.5%) also showed c-myc protein expression. Eight of 18 malignant melanomas(MM) (44.4%) showed expression of bcl-2 protein and 7 of these 8 cases (38.9%) also showed c-myc protein expression. All seborrheic keratoses and squamous cell carcinoma(SCC) were negative for bcl-2 proteins. 12 of 15 SCCs(80%) were positive for c-myc protein. In conclusion, bcl-2 and c-myc proteins were coexpressed in BCCs, nevi, and MMs. Coexpression of bcl-2 and c-myc proteins in these tumors was statistically significant(p<0.01), while no considerable differences of bcl-2 and c-myc expression were found between nevi and MMs. These results suggests that bcl-2 may cooperate with c-myc to promote tumorigenesis of BCCs, nevi, and MMs(p<0.01).

Morphological and Biochemical Study on the Processes of Apoptosis Induced by Radiation.: Kye Yong Song, Seong Man Kang, Seong Hwan Ha, Sang Chul Park; Korean J Pathol. 1996;30(9):819-829.

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Abstract PDF: Transglutaminase(TGase) is a calcium dependent enzyme that catalyse and acyl transfer reaction forming epsilon-(gamma-glutamyl)-lysine cross linkage. the major known effect of TGase is its important role in the programmed cell death manifested in the granular layer of the skin and acidophilic bodies in the viral hepatitis and neoplastic processes. The enzyme activity, immunohistochemical reaction using polyclonal antibodies against cytosolic TGase C, light and electron microscopic studies and TdT staining of the transplanted fibrosarcoma cells in C3H mouse with radiation therapy were done. The presence of TGase was detected immunohistochemically by avidin-biotin peroxidase complex (ABC) method Apoptosis were significantly induced after irradiation dependent with time factors and irradiation doses, resulted in marked and confluent tumor cell loss. Highest activity of the cytosolic form of TGase was noted at 24 hours and decrease after then while membrane bounded form of the TGase showed no significant changes. Immunohistochemical staining revealed strong positive reaction in the sarcoma cells in diffuse fasion and around the necrotic foci in the cytoplasm. Terminal dideoxynucleotidyl transferase(TdT) staining revealed increasing numbers of apotptic cells from two hours after irradiation. In the mechanism of decreasing tumor size and cell death in radiation therapy, apoptosis plays an important role and during that process transglutaminse might do some irreversible cross-linking effects of cytoplasmic proteins causing cell death in part.

Case Reports

Creutzfeldt-Jakob Disease: Histopathologic, Electron Microscopic and Immunohistochemical Studies of 2 Cases.: Duck Hwan Kim, Yeon Lim Suh, Duck Ryul Na, Won Kyu Joo, Yong Sun Kim; Korean J Pathol. 1996;30(9):830-838.

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Abstract PDF: Creutzfeldt-Jakob disease(CJD) is characterized clinically by rapidly progressive dementia with pyramidal, extrapyramidal, and cerebellar symptoms and signs, and histologically by spongiform change, neuronal loss and reactive gliosis. We have experienced 2 cases of CJD. Case 1 was a 36-year-old male who had suffered from myoclonus and cerebellar symptoms including sluggish speech, gait and balance disturbance. Case 2 was a 70-year-old female who had showed cognitive dysfunction, ataxic gait and disturbance of extraocular movement. Both patients, underwent brain biopsy.
Case
1 revealed marked cortical atrophy, 2mm in thickness, with neuronal loss and astrocytic proliferation extending into white matter. The spongiform change, made up of many small, usually rounded or oval, vacuoles was noted mainly in the neuropil. Case 2 revealed remarkable spongiform change throughout the cortex and cytoplasmic vacuoles compressing the nuclei of neuronal cells were numerous. Neuronal loss and gliosis were also found without considerable change in the white matter. On double immunostaining against GFAP and PrP(Prion Protein), there was a weak positive reaction for PrP in the perinuclear cytoplasm in case 1, and a strongly positive reaction in case 2. The electron microscopic examination showed numerous membrane-bound vacuoles in neuropil and perikarya of neurons. The majority of the vacuoles were multiseptated by thin membranous structures. They demonstrated curled, or disrupted membrane, that had foldings and protrusions into the vacuolar clear spaces. There were neither identifiable virus-like particles nor amyloid deposition.

Goblet Cell Carcinoid of the Appendix: A case report.: Joo Heon Kim, Ho Lee, So Young Oh, Myoung Jae Kang, Ho Yeul Choi, Dong Geun Lee; Korean J Pathol. 1996;30(9):839-842.

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Abstract PDF: Carcinoid tumors of the appendix are common incidental findings, but appendiceal tumors with histologic features of both carcinoids and adenocarcinomas are rare, and their biologic behavior and histogenesis are still unclear. We report a case of goblet cell carcinoid of the appendix in a 54-year-old male, who exhibited pain in the right lower abdomen. Microscopically, the tumor contained smooth-bordered, widely separated nests composed of tumor cells with abundant mucin. The principal tumor cell type had a close resemblance to the normal goblet cell. Histochemically, the tumor cells revealed positive reaction for PAS and alcian blue stain. Immunohistochemically, the tumor showed strong reactivity for carcinoembryonic antigen, chromogranin and, neuron specific enolase but none for cytokeratin and epithelial membrane antigen.

Original Article

Mucinous Adenocarcinoma of Anal Ducts.: Young Ha Oh, Wan Seop Kim, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1996;30(9):843-850.

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Abstract PDF: Anal duct carcinoma is a rare tumor, and accounts for less than 5 percent of all anal cancers, which typically present a long-standing perianal fistulas. Some authors suggest that the fistulous tracts are congenital duplications of the lower end of the hind gut lined by rectal mucosa which is prone to malignant change to mucinous adenocarcinoma. It is usually a well differentiated mucinous (colloid) adenocarcinoma. The prognosis after wide excision of the rectum is relatively good. Since 1985, we have had three cases of anal duct carcinoma with well differentiated mucinous adenocarcinoma involving the posterior wall of the anus. Two patients had a long history of perianal fistula with mucinous discharge. There was no spread to the regional lymph node except one patient who had regional lymph node metastasis, and post-operative chemotherapy and radiation therapy were then given. All patients have no evidence of any recurrent problem at 16 months to 3 years following the surgical treatment. Because of their rarity and the failure of recognition at an early stage, we are presenting three cases to emphasize the characteristic features of this insidious, slow-growing carcinoma.

Case Reports

Metastatic Gestational Trophoblastic Disease in the Lung Occuring with Hydatidiform-mole in Tubal Pregnancy: A case report.: Hee Jeong Ahn, Kyu Rae Kim, Chang Jo Chung; Korean J Pathol. 1996;30(9):851-853.

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Abstract PDF: Gestational trophoblastic disease associated with the tubal pregnancy is uncommon, and the incidence has been described as 1/5000 tubal pregnancy. We have experienced a case of metastatic gestational trophoblastic disease(GTD) in the lung occuring with complete hydatidiform mole arising in tubal pregnancy. The patient was a 39-year-old, G4P2A2L2 woman with amenorrhea for 5 weeks. Ectopic pregnancy in the right fallopian tube was suspected on transvaginal ultrasonogram. A right adnexectomy was performed. The fallopian tube was markedly dilated and ruptured. The right ovary and a round hematoma had adhered to the external surface of the fallopian tube. On gross examination, no molar tissue was identified. On microscopic examination, the lumen of the dilated fallopian tube was filled with blood clots admixed with several chorionic villi showing hydropic swelling and marked proliferation of atypical trophoblasts. Proliferating syncytio-and cytotrophoblasts invaded the wall of the blood vessels of the fallopian tube and sheets of trophoblasts and some villi were identified in the lumen of blood vessels. Multiple pulmonary nodules thought to be metastatic nodules were identified in the chest X-ray and serum beta-HCG had increased 2 weeks later. This case indicates that a careful pathological examination in the ectopic pregnancy is mandatory, because tubal GTD is not clinically distinguishable from ordinary tubal pregnancy.

Sarcoma-like Mural Nodule in Ovarian Mucinous Cystadenocarcinoma: A case report.: Suk Hee Lee, Min Hee Jung, Byung Yuk Lee, Jong Min Chae; Korean J Pathol. 1996;30(9):854-857.

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Abstract PDF: We describe an ovarian mucinous cystadenocarcinoma with a sarcoma-like mural nodule. In the literature, rare cases of ovarian mucinous tumors have been described which contain foci of undifferentiated carcinoma, sarcoma, and sarcoma-like nodules. The distinction between these lesions is important because of poorer prognosis of true sarcoma and anaplastic carcinoma than sarcoma-like mural nodules. This case shows different results of immunohistochemical stain for anaplastic carcinoma.

Invasive Extramammary Paget Disease: A Report of 2 Cases with Immunohistochemical and Ultrastructural Findings.: Kyu Rae Kim, Chong Woo You, Jeong Ho Han, Young Hyeh Ko; Korean J Pathol. 1996;30(9):858-864.

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Abstract PDF: We present 2 cases of invasive extramammary Paget disease occuring in the vulva area of a 60 year old female, and in the scrotal and penile area of a 63 year old male patient. The histologically typical Paget cells were not only seen in the surface epithelium but were also involved in the outer root sheath of the hair follicles. Stromal infiltration of tumor cells into the upper dermis were present in both cases, however, no underlying primary sweat gland carcinoma was present. Metastatic foci of inguinal lymph nodes showed apocrine-type epithelium with abundant eosinophilic granular cytoplasm, which were positive for anti-CEA and GCDFP-15, as well as eccrine-type epithelium containing mucinous secretory materials in the lumen and the cytoplasm. Ultrastructural findings showed interdigitating plasma membranes with prominent desmosomes between the Paget cells, intracytoplasmic tonofibrils, intracellular tubules, lipid vacuoles, and enlarged mitochondria. Histological, immunohistochemical, and ultrastructural findings suggested that Paget cells showed both eccrine and apocrine differentiation.

Desmoplastic Trichoepithelioma: A case report.: Jean A Kim, Young Sill Kim, Seok Jin Kang, Sun Moo Kim; Korean J Pathol. 1996;30(9):865-867.

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Abstract PDF: Desmoplastic trichoepithelioma is a solitary tumor of the hair follicle with female preponderance, most commonly located on the face. Clinically, the lesions appear annular and firm with a raised border and a depressed nonulcerated center, but the appearance is not so distinctive to hair follicle tumors that definite diagnosis is established by the histopathologic findings. We report a case of desmoplastic trichoepithelioma in a 67-year-old woman who had an asymptomatic, hard, annular lesion measuring 0.8 cm in diameter, with a raised border and a depressed center on the right cheek. Histopathologic findings showed narrow strands of basaloid cells, horny cysts, and desmoplastic stroma, with the features corresponding to the desmoplastic trichoepithelioma.

Clinical Pathology, Catholic University Medical CollegeSynovial Sarcoma Manifested as a Subcutaneous Nodule of Lip: A case report.: Jae Hwa Lee, Young Ok Kim, Bang Hur, Man Ha Hur; Korean J Pathol. 1996;30(9):868-871.

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Abstract PDF: Synovial sarcoma is one of the most common malignant soft tissue tumors in paraarticular regions. However, it is very rare to occur without any apparent relationship to synovial or articular structures. We report a case of synovial sarcoma manifested as a subcutaneous nodule in the upper lip. A 12-year-old boy complained of a palpable tender mass in the upper lip for several months. Under the impression of a benign soft tissue neoplasm, surgical excision was done. The mass, 1.5 cm in maximum diameter, was easily separated from surrounding tissues. Microscopically, this tumor showed a characteristic biphasic pattern of synovial sarcoma. On immunohistochemical and ultrastructural studies, the tumor cells showed evidence of epithelial differentiation. There was no evidence of joint-related, primary lesions or metastatic foci. This report describes a case of synovial sarcoma arising in very unusual location and size for histologically typical synovial sarcoma.

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