Journal of Pathology and Translational Medicine

Volume 31(5); May 1997

Original Articles

Grading System for Gastric Epithelial Proliferative Diseases Standardized Guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.: Hoguen Kim, So Young Jin, Ja June Jang, Woo Ho Kim, Sang Yong Song, Kyu Rae Kim, Eun Sil Yu, Hyung Sik Shin, Han Kyeom Kim, Jin Hee Sohn, Eun Kyung Hong, Youn Wha Kim, Jin Sook Jeong, Chang Jin Kim, Shin Eun Choi, In Suh Park, Chan Il Park, Yong Il Kim; Korean J Pathol. 1997;31(5):389-400.

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Abstract PDF: The assessment of epithelial changes in gastric mucosal biopsies has been one of the major problems caused by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, members of the Study Group for Pathology of Digestive Diseases reviewed microslides of 50 gastric lesions showing varying degrees of mucosal abnormality and reached the following consensus; 1) the proliferating gastric epithelium can be divided into hyperplastic and neoplastic; 2) the term "dysplasia" is reserved for the microscopic epithelial changes that are unequivocally neoplastic; 3) Biopsy specimens can be categorized as regenerative(negative for dysplasia), indefinite(questionable dysplasia), positive(positive for dysplasia) and overt carcinoma; 4) The positive category can be divided into two subgroups, high grade dysplasia and low grade dysplasia. Criteria for each grade are presented and discussed. We offer these guidelines for establishing the correct diagnosis of the gastric mucosal biopsy specimens and for prospective studies.

Immunohistochemical Study of the Vascular Endothelial Growth Factor in Gastric Carcinoma.: Tae Jung Jang, Jung Ran Kim; Korean J Pathol. 1997;31(5):401-409.

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Abstract PDF: Many studies have shown that angiogenesis plays an important role in the growth, the progression, and the metastasis of a solid tumor. The vascular endothelial growth factor(VEGF) is thought to be a selective mitogen for endothelial cells. Twenty eight advanced gastric carcinomas and twenty early gastric carcinomas were investigated by staining with polyclonal antibody against the VEGF. Correlation between the expression of the VEGF and the clinicopathologic features of gastric carcinoma were studied. The VEGF was mainly localized to the cytoplasm of carcinoma cells. Normal gastric foveolar epithelium was not immunoreactive, but some endothelial cells were weakly immunoreactive with an anti-VEGF antibody. Expression of the VEGF was significantly higher in advanced gastric carcinoma than in early gastric carcinoma (p=0.003). Expression of the VEGF was correlated with the depth of tumor, the lymph node metastasis, and the stage (p<0.05). The VEGF positivity was significantly higher in moderately and poorly differentiated gastric carcinoma than in well differentiated gastric carcinoma. The VEGF scores of the metastatic foci in the lymph nodes were higher than that of the primary tumors, which were followed by deep and superficial portions of the primary tumors in a descending order (p<0.05). In summary, the expression of the VEGF may be associated with progression and metastasis of a gastric carcinoma and may also be a good prognostic factor in a gastric carcinoma.

Correlation of Tumor Angiogenesis and nm23-H1 Expression with Lymph Node Metastasis in Proper Muscle Gastric Cancer.: Eun Sook Nam, Gu Kang, Hyung Sik Shin, Young Eui Park; Korean J Pathol. 1997;31(5):410-416.

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Abstract PDF: We studied clinicopathologic features of 44 cases of PM (proper muscle) gastric cancer, correlated the lymph node metastasis and found the result of immunohistochemical staining for tumor angiogenesis using antibodies to Factor VIII-related antigen and nm23-H1, known as meatastasis inhibitory substance. The results were as follows: 1) The average age of these 44 cases of PM gastric cancer was 55.1 years old (range 35-81). The ratio of male to female was 2.2 : 1. The tumor was located at the antrum of stomach in 72.7% of the cases. The average size of the tumor was 4.1 cm (range 0.6-9). The gross features were comprised of Borrmann type I (6.8%), II (29.6%), III (56.8%), IV (6.8%), respectively. The microscopic type was a diffuse type in 70.5% and an intestinal type in 29.5%. There were lymph node metastasis in 25 of the 44 cases (56.8%). 2) The microvessel count was higher in the lymph node positive group (average 69.3) than in the lymph node negative group (average 45.6) (P=0.004). There was a higher microvessel density in diffuse type, over 4 cm of tumor size, proximally located tumor, older than 50 years, Borrmann type II and IV, but there was no statistically significant correlation. 3) The more decreased expression of nm23-H1 was found in the lymph node positive group (56.0%) than in the lymph node negative group (31.6%), but showed no statistical significance (P=0.0142). There was no significant correlation between the expression of nm23-H1 and the other clinicopathologic factors. We suggest that the microvessel count of the tumor angiogenesis may be a prognostic factor for predicting lymph node metastasis and also help to determine the therapeutic modalities of PM gastric cancer.

Expression of bcl-2 Protein in Colorectal Adenoma and Adenocarcinoma and its Relationship with p53 and Apoptosis.: Ae Ree Kim, Seong Jin Cho, Nam Hee Won, Yang Seok Chae; Korean J Pathol. 1997;31(5):417-426.

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Abstract PDF: Either increased cellular proliferation or decreased death might result in an expansion of their numbers in the oncogenic process. Cellular apoptosis represents an autonomous suicide pathway that helps to restrict the cell number. However bcl-2 and mutant p53 inhibit programmed cell death. To determine whether the bcl-2 gene is activated during colorectal tumorigenesis and whether it has any relationship with p53 and apoptosis, we studied the expression of bcl-2 and p53 in the normal colonic mucosa, in the adenomatous polyps and in the adenocarcinomas using the immunohistochemical method. Also we evaluated the status of apoptosis using the in situ end labeling method. The bcl-2 immunoreactivity was restricted to the basal epithelial cells of all normal colonic mucosa and they were expressed in all adenomas and 86% of adenocarcinomas, especially in the superficial lesion of some tumors. Mutations of p53 were not found in the normal colonic mucosa, but they were present in dysplastic cells of adenomas (52%) and in cancer cells of the adenocarcinomas (47%). Apoptosis was confined to the tips of the normal colonic mucosa. It was more easily detected in the p53-positive adenomas than in the p53-negative adenomas (p=0.010). In the adenocarcinomas, the findings of apoptotic process are not related with p53 mutation (p=0.3) and bcl-2 expression (p=0.187). p53 and bcl-2 are probably one step of several apoptotic processes in the adenocarcinomas.

Immunohistochemical Localization of Extracellular Matrix Components in Diabetic Nephropathy.: Seung Sam Paik, Moon Hyang Park; Korean J Pathol. 1997;31(5):427-435.

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Abstract PDF: Normal human glomerular basement membrane (GBM) and mesangial matrix (MM) contain several different basement membrane components in varying degrees. The characteristic morphological and ultrastructural changes in patients with diabetic nephropathy are the thickening of the GBM and the expansion of the MM. In order to investigate the changes of extracellular matrix components in diabetes, the immunohistochemical localization was performed in 17 cases with different degrees using antisera to human collagen types I, III, IV, VI, fibronectin, and laminin. The following results were obtained: 1. The reactivity for collagen IV was increased in expanded MM in the diffuse glomerulosclerosis (GS). With the progression to the nodule formation, collagen IV was prominently decreased in the peripheral area of the nodules. 2. Collagen VI was increased in GBM and MM in the diffuse GS, it was especially prominent in the expanded MM. With the progression to nodule formation, collagen VI was prominently increased in the periphery of the nodules. 3. Interstitial collagen I and III were not stained in many of the cases with the diffuse GS. With the progression to nodule formation, these were slightly expressed. A lamellar pattern of positive reaction was noted at the periphery of the late nodular lesions. 4. Fibronectin was increased in GBM & MM in the diffuse GS, it was especially intense in the MM. With the progression to the nodule formation, the reactivity of antibody to the fibronectin was decreased. 5. Laminin was weakly stained along the GBM & trace in the MM, but was not changed in the nodular GS. In summary, the expanded mesangial matrix in the diffuse GS showed a markedly increased staining for collagen IV, fibronectin and collagen VI. Less intense linear staining for collagen VI, fibronectin, laminin, collagen IV and collagen III was noted along the GBM. In the nodular GS, the composition of the early nodules resembled that of the diffuse GS. However, the late nodular lesion of the nodular GS revealed decreased reactivity for collagen IV and fibronectin at the periphery of the nodule, where collagen VI and interstitial collagen I and III were increased in laminated pattern.

Histopathologic Analysis of the Repeated Renal Biopsies in the Course of Lupus Nephropathy.: Chong Woo Yoo, Hyun Soon Lee; Korean J Pathol. 1997;31(5):436-445.

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Abstract PDF: Lupus nephropathy shows a variable clinical course including remission, relapse and progression to renal failure. To examine the clinical or morphological parameters which might be related to the progression of lupus nephropathy, we have analyzed renal biopsies of 19 patients (M : F=5 : 14), who underwent repeated renal biopsies by morphology and morphometry. The average age of the patients was 22.8+/-9.0 years. The mean interval between two biopsies was 34.5+/-13.3 months. The first renal biopsies of these patients were diagnosed with WHO class IV (74%), class II (11%), class I (5%), class III (5%), and class V (5%). According to the clinical data the patients were divided into 3 groups, static, relapsing and progressive. At the time of the first biopsies, the amount of proteinuria in both the static and relapsing groups was significantly higher than that in the progressive group (P<0.05). The volume density of the renal cortical interstitium of the first biopsies in the progressive group was significantly greater than that in the static and relapsing groups (0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.02 micrometer3/micrometer3, P<0.05; 0.14+/-0.07 micrometer3/micrometer3 vs. 0.05+/-0.04 micrometer3/micrometer3, P<0.05). The activity index of the second biopsies in the relapsing group was significantly higher than that in the static group (2.7+/-0.6 vs 1.2+/-1.0, P<0.05). In the progressive group, the percentage of glomeruli with global sclerosis and the volume density of the renal cortical interstitium in the second biopsies was elevated over the first biopsies (P<0.05). Half of the patients in the static and relapsing groups underwent a morphologic transformation on the second biopsy. However, of the 7 patients in the progressive group, only one showed a transformation from WHO class IV to class III, suggesting that the transformation is not related to the progression of lupus nephropathy. These results suggest that interstitial expansion and heavy proteinuria at the time of the first renal biopsy may bode for poor prognosis in lupus nephropathy. Furthermore, they suggest that an increased histologic activity index could be related to the relapse of the disease.

Histopathologic Re-evaluation of Thymoma with Immunonhistochemical Study for bcl-2 and MIC-2 Protein.: Kyung Moo Yang, Mee Yon Cho, Soon Won Hong, Tae Seung Kim, Chan Il Park, Woo Ick Yang; Korean J Pathol. 1997;31(5):446-461.

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Abstract PDF: We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.

Correlation Between the Frequency of Apoptotic Bodies and Gleason Scores in Prostatic Cancer.: Hee Soo Yoon, Ho Jung Kim, Hea Soo Koo, Ok Kyung Kim, Sung Sook Kim; Korean J Pathol. 1997;31(5):462-469.

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Abstract PDF: Apoptosis (or programmed cell death) is defined by morphologic changes induced by a spectrum of physical and chemical agents. resulting in non-pathologic cell loss, which is relevant to a range of biological processes, including differentiation, development, maturation, and injury of cells as well as immunologic function. In this study, we examined the frequency of apoptotic bodies and mitoses (apoptotic and mitotic indices) in the tissue samples of 35 patients of prostatic carcinoma, which were grouped according to the Gleason scores, and 5 cases of benign prostatic hyperplasia. The indices were determined as the numbers of apoptotic and mitotic bodies per 100 tumor cells in hematoxylin eosin stained section. The apoptotic bodies were confirmed by the in situ nick end labelling method. The apoptotic and mitotic indices were observed more frequently in prostatic carcinoma than the benign hyperplastic prostatic tissues with a positive correlation between the frequency of apoptotic bodies and Gleason scores in prostatic cancer. In conclusion, an increased programmed cell death was correlated with the increasing malignant potential (higher Gleason scores) in prostatic cancer.

Case Reports

Clear Cell Chondrosarcoma Arising in Hyoid Bone.: Hae Jin Jeong, Sug Kyoung Ko, Myeng Sun Park, Hee Kyung Chang, Man Ha Huh; Korean J Pathol. 1997;31(5):470-475.

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Abstract PDF: Clear cell chondrosarcoma, first described by Unni in 1976, is distinguished from classical chondrosarcoma by a typical histological picture, mostly an epiphyseal site of origin, and relatively a benign clinical course. We present a case of clear cell chondrosarcoma arising from hyoid bone in a 70-year-old male. Histologically, large areas of closely packed cells with characteristic clear cytoplasm were seen in addition to the usual elements of a conventional chondrosarcoma. Our search and review of the literature did not reveal any reported case of clear cell chondrosarcoma arising from hyoid bone.

Sebaceous Carcinoma Occurred in a Patient with Recurrent Bowen's Disease.: Mi Ok Park, Hoon Kyu Oh, Yong Jin Kim, Jae Bok Park; Korean J Pathol. 1997;31(5):476-481.

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Abstract PDF: Sebaceous carcinoma is a rare malignant epithelial tumor and has diverse clinical presentations as well as a variety of histologic patterns. Although the overwhelming majority of sebaceous carcinomas occur on the eyelid, they may also arise where sebaceous gland and hair are found together, but they favor the head and neck. We report a case of sebaceous carcinoma of the umbilicus in a 68-year-old man who had suffered from a long standing recurrent Bowen's disease of 23 years. The recurrent Bowen's disease in this patient appeared to be closely related to multiple arsenic medication 49 years and 39 years earlier. The excised specimen of umbilicus revealed a well demarcated, 1.5x1 cm sized tumor with grey-yellow hue. The tumor was identified as sebaceous carcinoma, which was characterized by lobular and comedo-carcinoma patterns. The tumor cells showed cytoplasmic foamy vacuolation, nuclear pleomorphism, and high mitotic activity. On an Oil-Red-O stain, the tumor cells were found to contain fine lipid droplets. The intracytoplasmic lipid vacuoles were demonstrated by an electron microscopic examination.

Achondrogenesis Type 2: An autopsy case.: Joon Mee Kim, Young Chae Chu, Soo Kee Min, Hee Jeung Cha, Je Geun Chi; Korean J Pathol. 1997;31(5):482-488.

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Abstract PDF: Achondrogenesis type 2 is a lethal form of congenital skeletal dysplasia characterized by severe short-limbed dwarfism, decreased vertebral ossification and normal ossification of the skull. We report an autopsy case of achondrogenesis type 2 in a female fetus terminated at 29 weeks of gestation. External morphology revealed a relatively large head, short upper and lower extremities, short neck, and distended abdomen. The x-ray finding showed normal calvarial ossification, hypoplastic ilium and unossified ischium, and metaphyseal flares of the femur and tibia. Histologically, chondrocytes were large and irregular with increased vascularity.

Eccrine Squamous Syringometaplasia.: Gyeong Sin Park, Lee So Maeng, Chang Seok Kang, Seok Jin Kang, Byung Kee Kim; Korean J Pathol. 1997;31(5):489-491.

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Abstract PDF: An eccrine squamous syringometaplasia (ESS) is defined as a mature squamous metaplasia of the eccrine ducts. The clinical and pathological features of an ESS are presented. Syringometaplasia is a rare lesion, mostly occuring in the extremities, and as far as we know, no report on the ESS has been published in Korean literature. We experienced a case of an ESS occured in a 15 year-old male, who had a tender erythematous plaque in the right knee. The histologic examination revealed some scattered nests of metaplastic squamous epithelium in the deep dermis, associated with acute nonspecific panniculitis. The importance of the ESS is that it histologically simulates the well differentiated squamous cell carcinoma. The histopathologic findings were discussed and a brief review of the literature was made.

Intrapulmonary Cystic Lymphangioma.: Mi Yeong Jeon, Je Geun Chi; Korean J Pathol. 1997;31(5):492-494.

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Abstract PDF: Solitary intrapulmonary cystic lymphangioma in newborn or infant is an extremely rare disease. We describe a case of solitary intrapulmonary cystic lymphangioma in a 4-month-old boy with dyspnea and tachypnea. It was in the left lower lobe and type 1 congenital cystic adenomatoid malformation was suspected radiologically. The resected cyst was unilocular with a thin wall, and was 9.5cm in size. Histologically, the cyst was lined by flattened endothelial cells supported by a minimal fibrous stroma.

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