- Molecular Subtypes of Primary Glioblastoma Identified by Gene Expression Profiling.
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Ghee Young Choe, S Mischel Paul
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Korean J Pathol. 2002;36(5):328-337.
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- BACKGROUND
The over-expression of the epidermal growth factor receptor (EGFR) occurs in nearly 50% of primary glioblastoma multiforme (GBM). Disruption of multiple signaling pathways is a critical factor in regulating the biological and clinical behavior of GBMs. In the future, therapy that specifically targets these disrupted pathways may represent the best potential treatment for patients with GBM. Large scale gene expression profiling provides a powerful approach to identify these disrupted genetic pathways and to uncover previously unknown molecular subtypes.
METHODS
We used 13 cases of primary GBM biopsy samples obtained from untreated patients and Affymetrix high-density oligonucleotide arrays to identify novel subsets of primary GBMs.
RESULTS
We showed that the expression of 90 genes differentiate EGFR+ from EGFR non-expressing (EGFR-) de novo GBMs, including expression of a number of potentially targetable molecules that act as growth/survival factors for GBMs. We also demonstrated the presence of two additional molecular subtypes of primary GBMs, including one characterized by the coordinate upregulation of contiguous genes on chromosome 12q13-15, which has a distinct global gene expression profile and expresses both astrocytic and oligodendroglial genes.
CONCLUSION
We have shown that there are EGFR+ primary GBMs, GBMs with coordinate upregulation of genes on chromosome 12q13-15, and primary GBMs lacking either alteration.
Moreover, they have distinct transcriptional profiles. Our findings strongly suggest that the three GBMs are biologically different tumor types, despite their identical microscopic appearance, and provide an important first step in developing a molecular taxonomy of GBMs.
- Cerebral Amyloid Angiopathy: A report of two cases.
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Kee Taek Jang, Ghee Young Choe, Yeon Lim Suh, Je Geun Chi
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Korean J Pathol. 1999;33(9):741-744.
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- Cerebral amyloid angiopathy (C.A.A) is characterized by the extracellular amyloid protein deposition in the vessel walls of the brain and meninges. It has been estimated to account for 5 to 10% of all primary, nontraumatic brain hemorrhage. We report two cases of C.A.A causing nontraumatic intracerebral hemorrhage in the frontal lobe. The first case was a 60-year-old female who was admitted for the left hemiplegia and dysarthralgia. Brain CT revealed right frontal lobe hemorrhage. The second case was a 72-year-old male who was admitted for amnesia and gait disturbance. Clinical impression was Alzheimer's disease. Brain MRI revealed multifocal small hemorrhage in the right frontal lobe. Microscopically, both cases showed dilated small arteries of superficial cortex and meninges with hyalinization. Some vessels showed microaneurysm and fibriniod necrosis. Congo-red stain also exhibited birefringence under polarized light.
There was no evidence of Alzheimer's disease.
- The Current Practice of the Autopsy Services and the Autopsy Records at the Seoul National University Hospital.
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Jeong Wook Seo, Yoon Sung Lee, Je Geun Chi, Ghee Young Choe, Soong Deok Lee, Chong Jai Kim, In Ae Park, Woo Ho Kim, Ja June Jang, Chul Woo Kim, Seong Hoe Park, Jung Bin Lee, Hyun Soon Lee, Yong Il Kim, Eui Keun Ham, Sang Kook Lee
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Korean J Pathol. 1998;32(6):453-459.
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Abstract
- This study outlines the current status of the autopsy practice and the medical records for autopsies at the Department of Pathology, Seoul National University Hospital.
Total number of autopsy cases from 1954 to 1995 was 3,131.
Adults aged over 17 were 371 cases and children were 2,515 cases. The demographic data in 245 cases was not available.
The number of adult autopsies and its proportion among total number of autopsies during 10-year periods decreased from 144 cases (40%) during the 10-year-period from 1956 to 52 cases (3%) during the 10-year-period from 1986. The number of children cases during the same period groups increased slightly from 210 cases (58%) to 393 cases (25%). But the number of fetal cases increased rapidly from 7 cases (2%) to 1,146 cases (72%). Among fetal autopsies the proportion of fetuses died earlier than 24 weeks of gestation increased and this figure exceeds that of fetuses that died later than 24 weeks of gestation from 1992. Forty percent of the cases were submitted from the clinical departments of the Seoul National University Hospital but the remainders were referred from 73 hospitals. Final autopsy diagnoses were analysed according to the Korean Standard Classification of Disease (KCD)-3 coding system and by searching key words for all cases. Common diagnoses as coded among cases from 1990 were P9, P0, P2, Q2 and Q0. Common diseases by key words for adult cases were liver disease, tuberculosis and pneumonia.
Common diseases for children cases were pneumonia, hyaline membrane disease, meningitis and tuberculosis. Through this study we could show the importance of autopsy services for fetuses. We could also establish a regular registration system for autopsies at general hospitals.
- Pathologic Analysis of 39 Cases of Epilepsy Surgery.
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Young Mee Cho, Joong Koo Kang, Youn Mee Hwang, Jung Kyo Lee, Ghee Young Choe
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Korean J Pathol. 1996;30(5):388-395.
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- Pharmacologic therapy is still the primary management for epilpsy; however, surgical treatment is a reasonable therapeutic option for patients suffering from medically intractable seizures, especially temporal lobe epilepsy having a documented unilateral epileptogenic area. Thirty nine patients with pharmaco-resistant complex partial seizures underwent anterior temporal lobectomy and hippocampectomy in 38 cases and frontal cortisectomy in one case. On pathological examination, hippocampal sclerosis was a predominent pathologic finding and was identified in 18 cases. Other non-neoplastic lesions consisted of 5 cases of vascular lesions(2 cavernous angiomas, 2 arteriovenous malformations and 1 angiomatosis), 3 cases of fibrous nodule, 2 cases of cicatrical changes of cerebral cortex, and 1 case of parasitic infection. Neoplasms including two cases of oligodendroglioma and one case of anaplastic astrocytoma were also noted. In seven cases, there was no detectable lesion on gross and microscopic examination. On post-operative follow-up, seizures were completely terminated in most cases(31 cases, 79%). The rest of the patients also displayed marked alleviation of symptoms. The seizures tended to recur more aften among the patients with neoplasm or no pathologically detectable lesion. In order to detect any minute pathological lesion, thorough gross and microcsopic examinations are considered to be essential.
- Carcinoid Tumors of the Gastrointestinal Tract: Analysis of 36 Cases.
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Kyeong Cheon Jung, Hee Sung Kim, Sang Yong Song, Ghee Young Choe, Yong Il Kim
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Korean J Pathol. 1996;30(5):396-407.
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- We reviewed a total of 36 cases of gastrointestinal carcinoid tumors during a period of ten and a half years at Seoul National University Hospital, looking at their histologic and ultrastructural features, as well as immunohistochemical results, then we correlated these with location. The primary sites of carcinoid tumors were rectum(39%), stomach(25%), appendix(22%), small intestine(8%) and colon(6%), in order of frequency. The predominant histologic types by organ were mixed and solid(A) types in all location, the solid type(type A) in the stomach, and tubular type(type C) in the rectum. Six out of 8 cases of appendiceal carcinoid were type A and the other two cases were mucinous carcinoid. Tubular adenoma or adenocarcinoma was associated with 36% of the rectal carcinoids, with one case of carcinoid in the small intestine, and one(11%) of the gastric carcinoids was found near an adenocarcinoma. Metastasis was found in one case of ileal carcinoid(100%), one case of cecal carcinoid, 3 of gastric carcinoid(33%) and 2 of rectal carcinoid(14%).
Primary tumor size ranged from 1 to 7 cm. Tumor necrosis and endolymphatic tumor emboli were found in 57% and 43% of the metastatic carcinoids, respectively. PCNA index showed a borderline significant difference between metastatic and nonmetastatic groups(P value=0.063). The low prevalence of appendiceal carcinoid and the relatively high prevalence of gastric-rectal carcinoid may reflect a low chance of incidental appendectomy and frequent detection of gastrointestinal endoscopy.
- Clinicopathological Analysis of Laryngeal Leukoplakia: Clinical Follow-up and Immunohistochemical Expression of p53 and PCNA.
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Yang Soon Park, Sang Yoon Park, Soon Ae Oak, Gyung Yup Gong, Joo Ryung Huh, Eun Sil Yu, In Chul Lee, Ghee Young Choe
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Korean J Pathol. 1996;30(4):318-327.
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- Laryngeal leukoplakia is seen in a number of pathologic settings such as keratosis without atypia(KWOA), keratosis with atypia(KWA), squamous cell carcinoma in situ(CIS) and invasive squamous cell carcinoma, and it continues to be a confusing and controversial topic for both otolaryngologist and pathologist. This is largely due to the use of ambiguous and inconsistent terminology, the lack of unanimous agreement on the definition of these terms, failure of the clinician to obtain a representative biopsy, and the subjectivity of the pathologist interpreting the biopsy. To evaluate the applicability of the expression pattern of p53 and PCNA in borderline cases of histopathologic classification, we performed a histopathologic analysis of leukoplakia to includ clinical follow-up, correlation of disease progression and degree of atypia, and expression of p53 and PCNA according to the degree of atypia.
Histologically, laryngeal leukoplakia included seven cases of KWOA, fourteen cases of KWA (mild-2, moderate-8, severe-4), three cases of CIS, and one case of invasive squamous cell carcinoma. Keratosis with atypia, a moderate degree or more, showed a strong tendency to progress to invasive carcinoma(p<0.05). The degree of p53 and PCNA expression correlated with the degree of atypia(p<0.05).
p53-positive cases at the initial biopsy clearly tended to recur and develop into invasive carcinoma(p<0.01).
- Cytologic Features of Soft Tissue Lesions.
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Soon Ae Oak, Gyung Yub Gong, Ghee Young Choe, Jur Yung Hch, Eun Sil Yu, In Chul Lee
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Korean J Cytopathol. 1995;6(1):27-35.
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- We reviewed 93 cases of fine needle aspiration of skin\subcutaneous and soft tissue lesions with histologic confirmation. On the basis of the most prominent cytologic features, morphologic classification of the aspirates was done.
Neoplastic lesions of soft tissue were categorized as ; round cell, spindle cell, polygonal cell, well-differentiated and myxoid tumor. This classification is convenient to recognize and categorize most soft tissue tumors.
- Fine Needle Aspiration Cytology of Peripheral Neuroepithelioma of Soft Tissue: Report of A Case.
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Yang Soon Park, Soon Ae Oak, Gyung Yub Gong, Ghee Young Choe, Joor Yung Huh, Eun Sil Yu, In Chul Lee
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Korean J Cytopathol. 1995;6(1):62-66.
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- Peripheral neuroepithelioma (PNE) of soft tissue is a malignant neuroectodermal tumor arising from peripheral(nonautonomic) nerve. It may occur in both children and adults, and are highly aggressive neoplasms that rapidly give rise to metastatic disease and death. We exprienced a case of peripheral neuroepithelioma of soft tissue in the upper arm in a 18-year-old female. Cytologic features revealed small round cells with scanty cytoplasm occurring both singly and in clusters. The clusters frequently tended to form Homer-Wright rosettes. The cells had a round to oval nucleus with fine chromatin and inconspicuous nucleoli in a hemorrhagic background.
- Hairy Cell Leukemia: A case report.
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Jae Gul Chung, Gyung Yub Gong, Ghee Young Choe, Eun Sil Yu, In Chul Lee, Kun Choon Park, Sang Hee Kim
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Korean J Pathol. 1994;28(6):675-677.
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- Hairy cell leukemia is an uncommon lymphoreticular disorder which primarily involves bone marrow, spleen, and peripheral blood. Patients, mostly men, present with splenomegaly and pancytopenia usually. A 62-year-old man was admitted with an abdominnal mass which had grown slowly for 20 years. On physical examination, an enlarged spleen was palpated without tenderness. An abdominal CT scan showed a diffusely enlarged spleen, which measured 20 cm in greatest dimension.
In the peripheral blood, many atypical lymphocytes with abundant, delicate, surface projections were noted. They had tartrate-resistant acid phosphatase(TRAP) activity.
Thrombocytopenia (60,000/mm3) was observed in the complete blood counts, Other laboratory data were within normal limits. He underwent splenectomy. The submitted spleen measured 26x15x5 cm and weighed 2150 gm. It was well encapsulated and the outer surface was smooth. Cut surfaces were diffusely dark-red. White and red pulps were indistinct. There was no mass-like lesion. Microscopically, the spleen consisted of monotonous mononulcear cells which involved red pulp. The white pulp was diminished, and could be barely recognized. Cells had small round nuclei and abundant cytoplasm. Ultrastructurally, cells with numerous slender surface projections were noted. In Korea, hairy cell leukemia is exceedingly rare. We report a case of hairy cell leukemia with characteristic pathologic features of spleen as well as those of peripheral blood.
- Serous Cystadenoma of the Pancreas.
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Young Mee Cho, Gyung Yub Gong, Ghee Young Choe, Eun Sil Yu, In Chul Lee
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Korean J Pathol. 1994;28(5):522-527.
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- Pathologists and others have been calling the serous cystadenoma of the pancreas "microcystic cystadenoma", following Compagno and Oertel's proposal in l978 because it usually consists of innumerable small cysts (less than 2cm).
However, unilocular or predominantly macrocystic types of serous cystadenoma have been occasionally reported.
Therefore, they present a difficulty in precise preoperative and intraoperative diagnosis for their simi1ar gross appearance to other cystic lesions of the pancreas. We discovered two cases of macrocystic and unilocular serous cystadenomas of the pancreas which were lined by cuboidal to flattened epithelial cells. They contained PAS positive and D-PAS negative intracytoplasmic glycogen granules. The unilocular, macrocystic and microcystic patterns may represent a morphologic spectrum of a pancreatic neoplasm.
So we propose to use the term "serous cystadenoma" rather than microcystic cystadenoma.
- Distribution of Smooth Muscles in Hemorrhoids.
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Jae Gul Chung, Ghee Young Choe, Gyung Yub Gong, Eun Sil Yu, Jin Cheon Kim, In Chul Lee
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Korean J Pathol. 1994;28(2):154-159.
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- Hemorrhoids are one of the commonest disorders specific to the human. However, the pathogenesis is not well understood so far. Anal submucosa is largely composed of blood vessels, loose connective tissue and smooth muscles, forming muscular network around the venous plexuses. We analyzed the distribution of smooth muscles in the hemorrhoidal tissues.
Immunohistochemical stainings for desmin, vimentin, and Factor VIII related antigen were performed using six freshly frozen hemorrhoidal tissues. All of them were diagnosed as external hemorrhoids. Four anal tissues from Miles' operation specimen without hemorrhoids were used as normal controls. In all six cases, venous plexuses were variably dilated and smooth muscle cells were unevenly distributed.
In minimally involved areas, there were relatively sufficient amount of perivascular smooth muscles which were arranged in their bundles. In contrast, only single scattered cells or very small amount of smooth muscle bundles were noted around the dilated vascular plexuses in severely affected areas. In two severe hemorrhoidal tissue samples, vascular plexuses were markedly dilated and only single scattered smooth muscle cells were seen. In conclusion, the total amount of smooth muscles in the submucosa of hemorrhoid tissue was reduced than those of the normal controls. The degree of hemorrhoidal dilation was inversely related to the amount of smooth muscles. However, causal relation between diminution of submucosal smooth muscles and venous dilation remains to be clarified.
- Estrogen Receptor Analysis in Fine Needle Aspirates and Frozen Sections from Human Breast Carcinomas.
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Gyung Yub Gong, Se Hyun Ahn, Kun Choon Park, Ghee Young Choe, Eun Sil Yu, In Chul Lee
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Korean J Cytopathol. 1994;5(1):10-14.
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- The expression of sex steroid hormone receptors by neoplastic cells is an important predictor of response to hormone therapy. Thus, the selection of treatment modality is often based on the identification of receptors in tumor tissue. Various monoclonal antibodies of high specificity are now available for analyzing the estrogen receptor(ER).
With these antibodies, biochemical enzyme immunoassay and immunohistochemistry using histologic sections have been used for ER analysis. We used fine needle aspirates from 15 human primary breast carinomas for the analysis of ERs. The semiquantitative receptor values obtained in cytologic specimens were correlated well with those from histologic specimens. The results of ER in fine needle aspirates were concordant with ER in histologic specimens(r=0.94). Only three cases showed a little difference in staining intensity and proportion of positive cells. Our results showed a good correlation between the receptor values determined in cytologic smears and those determined in tissue sections. It is suggested that measurement of the ER in cytologic smears may be a reliable technique which can be performed on aspiration cytologic samples.
- Combined Hepatocellular-Cholangiocarcinoma: Analysis of 8 cases with special reference to their growth patterns.
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Yong Il Kim, Geun Kook Lee, Woo Ho Kim, Eun Sil Yu, Ghee Young Choe
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Korean J Pathol. 1992;26(3):229-241.
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- Eight cases of combine hepatocellular-cholangiocarcinoma(HCC-CC) of the liver were analysed along with their growth patterns and histologic subtypes to draw a possible implication in understanding of their histogenesis. The relative incidence of combined HCC-CC among the surgically resected primary carcinomas of the liver(485 cases) was 1.6%. The combination patterns varied and were classified as follows; the multinodular tumor, each consisting of HCC or CC element(type 1) was found in 1 case, the single tumor mass with two distinct compartments of HCC and CC(type 2) in 3, and the single tumor with random mixture of two elements(type 3) comprised the remaining 4 cases. Of the 7 cases of single tumor mass(type 2 and 3) HCC and CC comprised the major component in 5 and 2 cases, respectively. The histologic features of both HCC and CC elements were not different from those of isolated HCC and CC, except for two of CC element in type 3 which disclosed the intermediated differentiation or socalled cholangiolocellular carcinoma in part. We conclude that there is no significant difference in the relative incidence of combined HCC-CC among primary carcinomas of the liver and their subtypes compared to that in other countries, regardless of high incidence of both HCC and CC in Korea. Also, we discussed a possible histogenisis along a hypothesis that some of the combined HCC-CC be the consequence of interposition of different cell type from a new subclone into the growth of an initial single cell type of primary carcinoma of the liver.
- Primary Appendiceal Papillary Adenocarcinoma of Colonic Type: Report of a case.
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Yun Kyung Kang, Ghee Young Choe, Yong Il Kim, Kuk Jin Choe
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Korean J Pathol. 1992;26(3):306-309.
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- We report a case of colonic type-papillary adenocarcinoma of appendiceal origin in a 73-year-old male patient. The patient presented with right lower quadrant mass and was operated for a preoperative diagnosis of inflammatory small bowel mass. The mid one-third of the appendix showed a 3.5x3.3 cm sized, broad-based, intraluminal papillary mass.
Microscopically, it was a well differentiated papillary adenocarcinoma and revealed a strong immunoreactivity to carcinoembryonic antigen. Tumor desmoplasia and acute inflammatory change were prominent.
- Pseudolipomatosis of the Gastrointestinal Mucosa: Report of 6 cases with analysis of possible factors involved during endoscopic procedure.
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Ghee Young Choe, Yong Il Kim, Kyoo Wan Choi, Kee Suk Hong
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Korean J Pathol. 1992;26(1):10-16.
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- Pseudolipomatosis of the colonic mucosa has been recognized as a lesion featured with aggregations of gaseous spaces in the lamina propria, but its pathogenesis remains still unclear. This paper describes 6 cases of pseudolipomatosis occurring in the mucosa of stomach and large intestine, and the possible factors involved in gastrointestinal endoscopic procedure to produce gaseous entrapment in the lamina propria were analysed. All cases received either gastroscopy or colonoscpy before endoscopic biopsy. Mucosal tissues from both stomach and recto-sigmoid colon revealed multiple aggregations of small air-spaces resembling fatty infiltration in the lamina propria. Rarely were similar infiltrations within the muscularis mucosae and adjacent lymphoid follicles. Evidence for pneumatosis cystoides intestinalis or ulcerative colonic lesion was not associated, although one showed a small gastric ulcer nearby. Repeated inflations and deflations of the stomach or colon during the endoscopic procedure with miner mechanical trauma by instrument to the mucosa seem to contribute to its pathogenesis.
- Immunohistochemical Expression of Neuron Specific Enolase-Positive Cells in Gastric Adenocarcinomas.
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Ghee Young Choe, Yong Il Kim
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Korean J Pathol. 1991;25(4):291-304.
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- In order to correlate the frequency of neuroendocrine cells with pathologic parameters in gastric adenocarcinomas, immunoperoxidase staining for neuron specific enolase was performed on 250 consecutive cases of surgically resected gastric adenocarcinomas(201 advanced gastric carcinomas[AGCs], 49 early gastric carcinomas[EGCs] and 2 cases of gastric carcinoid tumors. Of the 252 cases of gastric carcinomas, pure exocrine carcinomas were 174 cases(69%), pure neuroendocrine(NE) carcinomas 2 cases(0.8%), mixed exocrine and NE carcinomas 32 cases(12.7%), and exocrine carcinomas with occasional NE cells 44 cases(17.5%). The frequency of gastric carcinomas with NSE-positive cells increased with age proportionally.
NSE positivity was higher in polypoid or fungating tumors(AGC Borrmann type I, II, EGC I and IIa) than ulcerative or scirrhous tumors. There was no significant difference in frequency of NSE-positive cells by histologic type and differentiation of gastric adenocarcinomas. The above findings reflect that most gastric carcinomas are heterogeneous in their constituents and suggest that both exocrine and neuroendocrine carcinomas are the expression of the extreme ends of the exocrine-endocrine differentiation spectrum based on the assumption that they develop from the pluripotent stem cells differentiating into both exocrine endocrine carcinomas.
- Computerization of 100,000 cases of Surgical Pathology Data at SNUH by Automatic Coding System using Personal Computer.
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Woo Ho Kim, Ghee Young Choe, Jeong Wook Seo, Yong Il Kim
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Korean J Pathol. 1990;24(4):509-512.
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- A computer program using automatic coding of the diagnosis has been used for report printing as well as data storage and retrieval system at the Department of Pathology, Seoul National University Hospital. Previous surgical pathology files were also computerized by the automatic coding system using personal computer, and 100,000 cases of surgical pathology data during 7 years were computerized at present.
The cpmputerized surgical files were counted and listed according to topograph and morphologic diagnosis. It is available to print out the list of a specific diagnosis or to copy the records to a floppy diskette. Collection of cases in surgical pathology files using cpmputerized automatic coding system becomes much convenient and accurate than using stored file cards or log books. In addition, previous biopsy records of the patient are automatically searched during the routine work so that understanding of a patient as a whole is possible through the informations about previous pathologic diagnosis. We confirm that automatic coding methods is the most practical and economic method for computerization of the surgical pathology records.
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