Journal of Pathology and Translational Medicine

Volume 29(1); February 1995

Original Articles

The Role of Ito Cell in Hepatic Fibrosis after Common Bile Duct Ligation: inhibitory role of vitamin A in Ito cell.: Kyung Hee Park, Sang Han Lee, Jong Min Chae; Korean J Pathol. 1995;29(1):1-9.

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Abstract PDF: The purpose of this study was to investigate the inhibitory role of vitamin A with respect to activation of Ito cells in fibrosis of the rat liver induced by common bile duct ligation(CBDL). The liver was examined by immunohistochemical staining for a-smooth muscle actin,the known marker of activated Ito cells, and light and electron microscopy after CBDL andCBDL with intraperitoneal injection of retinoic acid (Sigma, USA) 1 mg/Kg in 3 times per week. The results were sumrrlerized as follows: After CBDL, the bile ductules were markedly proliferated in the periportal areas extending toterminal hepatic veins. Interstitial fibrosis and inflammatory cell infiltration appeared, however,cholestasis was minimal. Retinoic acid treatment with CBDL decreased bile ductular proliferationand interstitial fibrosis compared to CBDL only. After CBDL, proliferated and activated Ito ceIs showing positive reaction in smooth muscle actin were present in the periductular andperisinusoidal areas, and areas of increased interstitial fibrosis. Activated ito cells weredecreased in number after CBDL with vitamin A treatment. Electron microscopically,intracytoplasmic fat droplets and the cytoplasmic processes of Ito cells were decreased afterCBDL. Myofibroblasts were frequently appeared in the interstitial fibrosis after CBDL. But,intracytoplasmic fat droplets of Ito cells were well preserved, and myofibroblasts were found lessfrequently after CBDL with vitamin A treatment. The results suggest that vitamin A plays an inbitory role in the activation and fibrogenesis ofIto cells after CBDL.

Ultrastructural Study of Amiodarone-Associated Lung Injury.: Eun Yung Kim, Sang Han Lee, Yoon Kyung Sohn, Tae Joong Sohn; Korean J Pathol. 1995;29(1):10-23.

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Abstract PDF: Amiodarone, an antiarrhythmic drug, may exert pulmonary toxicity in some patients but the pathogenesis is not clear. This study was carried out to investigate the pathogenetic mechanism of pulmonary injury induced by amiodarone at dose of 100 mg/kg/day given to rats by intraperitoneal injection for 3 weeks. And the preventive effects of concomitantly injected steroid (10 mg/kg/day) on amiodarone induced pulmonary injury was also studied using bronchoalveolar lavage, light microscopy and transmission electron microscopy. The results obtained were summarized as follows: Mild lymphocytosis of bronchoalveolar lavage fluid was found in all experimental groups. Intracytoplasmic lamellar body formation was found in all types of pulmonary cells and type II pneumocytes revealed the earliest abnormal lamellar body formation. The capillary endothelial cells showed cellular swelling and detachment from underlying basement membrane at early phase of experiment and the edema of alveolar wall and interstitium were noted. Interstitial fibrosis and proliferation of type II pneumocytes were noted at late phase. The lungs of steroid injected groups revealed accumulation of lamellar bodies in all types of pulmonary cells but interstitial fibrosis was not occurred. These findings support the concept that amiodarone is responsible for a drug-induced phospholipidosis and directly toxic to pulmonary endothelial and epithelial cells. And steroid may regress the progression of amiodarone induced pulmonary injury.

The Effect of Dehydroepiandrosterone on Inhibition of Carcinogenesis and Induction of Apoptosis in Murine Hepatoma Model.: Kye Yong Song, Eun Sup Park, Jee young Choi, Sang Chul Park; Korean J Pathol. 1995;29(1):24-32.

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Abstract PDF: Tumor suppressive effect of dehydroepiandrosterone (DHEA) on the experimentally induced hepatocellular carcinoma was investigated, especially focusing on glutatione transferase and transglutaminase with aptosis in the carcinogenesis. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into AA group treated by the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-acetamidofluorene (AAF) and AD group treated with DHEA simultaneously with AAF and the AAD group treated by DHEA after treatment with AAF. Each group was divided by time sequence further into four subgroups, GI (8wk), G2 (16wk), G3 (28wk), and G4 (36wk). For neoplastic lesion, the immuno histochemical study with anti GSTP antibody was carried out, while the activity and expression of TGase was compared at the same time. The results were summarized as follows; GST-P positive foci detected in AD groups were significantly more suppressed by DHEA treatment than AA groups (P<0.05). AD groups. AD group showed higher activities of TGase than AA groups (P<0.05), which was confirmed by Western and Northern blot analysis. But the number of apoptotic bodies was not correlated with activity and expression of TGase in the nodule. These results suggest that the suppressive effect of DHEA on the murine hepatocellular carcinogenesis might be operating on the promotion process of carcinogenesis rather than regression process of transformed hyperplastic nodules.

Histological and Immunohistochemical Findings of the Endometrium in Ectopic and Intrauterine Pregnancy.: Yee Jeong Kim, Soon Won Hong, Kyu Rae Kim, Chanil Park; Korean J Pathol. 1995;29(1):33-39.

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Abstract PDF: We reviewed histological and immunohistochemical findings of the endometrium in 28 cases of ectopic pregnancy and 11 cases of intrauterine pregnancy without chorionic villi or syncytiotrophoblast. 1) Twenty cases(71.41/o) of ectopic pregnancy revealed gestational patterns and 8 cases(28.6%) showed non-gestational patterns, which were menstrual phase in 3 cases, proliferative phase in I case, early secretary phase in 3 cases and mid secretary phase in 3 cases, respectively. Implantation sites were present in 36.40/o of intrauterine pregnancy. 2) Endometrial spiral arterioles tend to be more prominent with frequent intimal proliferation and thickening of the wall in intrauterine pregnancy than in ectopic pregnancy although it was not statistically significant(p=0.271). 3) Deposition of fibrinoid material in the endometrium was present in 72.7% of intrauterine pregnancy and 25% of ectopic pregnancy. Thrombosis was present in 72.7% of intrauterine pregnancy and 5% of ectopic pregnancy. Hyalinized vessels were also present in 90.9% of intrauterine pregnancy and 200/o of ectopic pregnancy. These were statistically significant(p=0.0002, 0.0209 and 0.0004), but not diagnostic. 4) On immunohistochemical study for intrauterine pregnancy, the rates of positive reaction to human placental lactogen, cytokeratin and human chorionic gonadotropin were 45.5%, 45.5% and 9%, respectively. We concluded that HFIL and cytokeratin are reliable and sensitive markers for implantation site.

Clinico-Pathological Characteristics of Congenital Megacolon.: Soon Young Kim, Jeong Kee Seo, Kwi Won Park, Woo Ki Kim, Je G Chi; Korean J Pathol. 1995;29(1):40-51.

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Abstract PDF: This study is based on 155 patients of congenital me colon. For the diagnosis, 93 cases were histologically proven and the remaining 63 cases were diagnosed on clinical basis including barium enema or surgical gross findings. On histologic examination, 80 cases(86%) showed typical features of absence of ganglion cell in the myenteric plexus and the 13 cases(14%) had atypical features which were segmental absence Of ganglion cell in one case. There we 127 males(82%) and 28 females(18%). The age at diagnosis was younger than 30 days in 87 cases(56%), I month to 1 year in 39 cases(25%) and older than I year in 29 cases(18%). The levels of aganglionosis were variable: short segment (rectosigmoid) in 134 cases(86%), intermediate segment (more proximal colon) in 14 cases(100%). and 6 cases(4%) had total aganglionosis. Common clinical presentations were abdominal distention, delayed meconium passage or bilious vomiting in neonate, and chronic constipation in infancy or childhood. Following initial colostomy or ileostomy, a definitive procedure was performed in 151 cases(Duhamel type in 150 cases; Soave type in 2 cases; Swenson type in 3 cases). Frequently associated problems after definitive procedure were persistent constipation(ll%) due to septum formation, fecaloma, remnant aganglionic segment and rectal stenosis. Overall mortality rate was 4%, and increased mortality was associated with enterocolitis(14%) which was the most frequent cause of death. The follow-up study longer than 3 months was available in 138 patients who underwent a definitive procedure(mean 2 year 11 months). Seventy-three cases(53%) had normal bowel function, 38cases(27.5%) had occasionally used enema or stool softners, and 27 cases(19.5%) had severe constipation or soiling. The bowel habit improved with time, and were considered normal in 60% of patients after follow-up more than 3 years. The results of definitive procedures for congenital megacolon including Duhamel operation was satisfactory, and long-term follow-up appeared an important and critical component of patients'care.

Immunohistochemical Characteristics According to Histologic Differentiation and Flow Cytometric Analysis of DNA Ploidy in Neuroblastic Tumors.: Jai Hyang Go, Woo Hee Jung, Soon Hee Jung, Tai Seung Kim, Chanil Park; Korean J Pathol. 1995;29(1):52-60.

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Abstract PDF: Neuroblastoma, ganglioneuroblastoma and ganglioneuroma are derived from primordial neural crest cells and can be conceptualized as three different maturational manifestations of a common neoplasm. To assess the validity of immunohistochemistry and DNA Ploidy in the diagnosis of neuroblastic tumor in terms of prognostication, histologic and immunohistochemical evaluation with NB-84, neuron specific enolase(NSE) and S-100 protein and flow Cytometric DNA analysis were done on 21 neuroblastomas and 19 ganglioneuromas. Thirteen of 21 neuroblastomas were undifferentiated and 8 differentiating in type. Eleven of the 19 ganglioneuromas were mature in type and 8 had immature foci. Eighty one percent of neuroblastomas were positive for NB-84, 100% for NSE and 67% for S-100 protein, respectively. All ganglioneuromas were positive for NSE and S-100 protein, in contrast, only immature foci in ganglioneuroma were positive for NB-84. B-84 reacted positively with undifferentiated and differentiating neuroblasts including neuropil but not with mature ganglion cells. In contrast, NSE reacted positively with all components of neuroblastic tumor and S-100 protein mainly with cells of Schwannian differentiation. Three of eight(37.5%) differentiating neuroblastomas were strongly positive for NB-84 in contrast with seven of thirteen(53.8%) undifferentiated tumors, reflecting that undifferentiated cells tended to be positive for NB-84 in neuroblastoma. Twenty two percent of neuroblastoma showed diploidy and 78% aneuploidy including 11% of near-diploidy. Seven of eight(87.5%) differentiating neuroblastomas in contrast with seven of ten(70%) undifferentiated tumors showed aneuploidy. By contrast, 53% of ganglioneuroma showed diploidy and 47% aneuploidy with DNA index ranged from 1.12 to 1.19. Three of nine(33.3%) mature ganglioneuromas in contrast with five of eight(62.5%) ganglioneuromas with immature foci showed aneupolidy. Differentiating neuroblastoma tended to be aneuploid and ganglioneuroma with immature foci tended to be near-diploid. In conclusion, immunohistochemistry for NB-84, NSE and S-100 protein is useful for confirming neuronal, both neuronal and Schwannian, and Schwannian differentiation, respectively. Immunohistochemistry together with flow cytometric DNA analysis would be helpful to confirm the immature foci in ganglioneuroma.

Diagnostic Significance of the CEA, AgNORs and PCNA in the Gastric Dysplasia and Adenocarcinoma.: Weon Cheol Han, Hyung Bae Moon; Korean J Pathol. 1995;29(1):61-67.

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Abstract PDF: This study aimed to differentiate gastric mucosal lesions such as the inflammatory gastric mucosa, gastric dysplasia and adenocarcinoma, using the CEA(carcinoembryonic antigen), AgNORS(Nucleolar organizer regions) and PCNA(proliferating cell nuclear antigen) stains. The tissue samples were taken from 30 cases of inflammatory gastric mucosa (19 gastritis and 11 regenerative hyperplasia), 28 cases of gastric dysplasia (9 mild dysplasia, 10 moderate dysplasia and 9 severe dysplasia) and 21 cases of gastric adenocarcinoma. The CEA was expressed in 16 of 21 adenocarcinomas(76%), but in neither inflammatory nor dysplastic gastric mucosae. The mean number of AgNORs per nucleus was 1.54 in inflammatory gastric mucosa, 1.80 in gastric dysplasia, and 1.88 in adenocarcinoma. The number of AgNORs was increased in dysplasia and adenocarcinoma compared to the inflammatory gastric mucosa without statistical significance. The percentage of the PCN A positive cells was 35.2% in inflammatory gastric mucosa, 44.1 % in gastric dysplasia, and 69.0% in gastric adenocarcinoma. The positivity of the PCNA was significantly increased in adenocarcinoma compared to the inflammatory gastric mucosa and dysplasia. In conclusion, the frequency of the CEA positive staining was increased in the gastric adenocarcinoma, and so CEA stain will be able to provide an additive method for the differential diagnosis between severe dysplasia and adenocarcinoma of the stomach.

Correlation of Histologic Findings of Ovarian Epithelial Tumors with Expression of Proliferating Cell Nuclear Antigen and Flow Cytometric DNA Analysis.: Sang Yeop Yi, Soon Hee Jung, Kwang Gil Lee; Korean J Pathol. 1995;29(1):68-76.

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Abstract PDF: The prognosis of malignant ovarian tumor is poorer than that of borderline malignant ovarian tumor, Therefore an accurate diagnosis and estimation of the biologic behavior of the tumor are necessary for proper management of the patient. The histologic investigation of the tumor may provide information on the estimation of the malignant potential of tumor cells, but it may be a questionable method because of the subjective determination of tumor grade. Quantification of proliferative activity of tumor cells may play a role as an objective method to provide an estimation of the malignant potential of tumor cells. An evaluation of histologic findings was done on 84 cases of ovarian mucinous and serous tumors that were surgically resected and diagnosed during the period from January 1981 through July 1992. The proliferating cell nuclear antigen (PCN A) labelling index estimated from the immunohistochemical stain for PCN A and the Sphase fraction and porliferative index obtained from flow cytometric DN A analysis were assessed each other with histologic findings. The results are as follows: The presence of aneuploidy in malignant tumors was statistically significant as compared with benign tumors. The borderline malignant tumors showed no significant difference between the number of diploidy and aneuploidy. The PCNA labelling index, S-phase fraction and proliferative index tended to increase as the histologic grade of tumors went up. They were higher in malignant tumors than in others. The PCN A labelling index, S-phase fraction and proliferative index were higher in tumors with aneuploidy than in those with diploidy. In contrast to borderline malignant tumors, the PCNA labelling index in malignant tumors revealed a significant relation with the mitotic index. The S-phase fraction and proliferative index showed, in malignant tumors, a close correlation with the architectural grade and nucleolar grade, but not in borderline malignant tumors. Considering these results, the presence of aneuploidy, PCNA label.

Immunohistochemical Study on the Proliferative Activity of Human Thyroid Tumors.: Myoung Jae Kang, Young Jin Jeong, Woo Sung Moon, Myoung Ja Jeong, Joo Heon Kim, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim; Korean J Pathol. 1995;29(1):77-84.

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Abstract PDF: For the estimation of the proliferative activity, related to the biologic behaviour, malignant potential, and prognosis, of human thyroid tumors, PCNA(proliferating cell nuclear antigen) immunohistochemical staining was performed on paraffin-embedded sections of 9 normal thyroid tissues, 9 adenomatous goiters, 9 follicular adenomas, 4 Hurthle cell tumors, 12 papillary carcinomas, 4 follicular carcinomas, and 3 anaplastic carcinomas. The results were as follows: 1) The PCNA labeling indices in adenomatous goiter, follicular adenoma, and Hurthle cell tumor were 1.1, 1.5, and 2.4, respectively. They were significantly higher than the labeling index in normal thyroid. 2) The PCNA labeling indices in papillary carcinoma and follicular carcinoma were 3.5 and 4.4, respectively. They were significantly higher than the labeling indices in adenomatous goiter and follicular adenoma, but there was no significant difference between papillary and follicular carcinoma. 3) The PCNA labeling index in anaplastic carcinoma, 14.1, was significantly higher than those in benign and other malignant tumors. According to the results, the PCNA labeling index was well correlated with the malignant potential of a tumor. So the PCNA immunohistochemical staining is thought to be a useful method for the evaluation of the malignant potential and prognosis of a tumor.

Case Reports

Malignant Mixed Germ Cell Tumor and Contralateral Gonadoblastoma in Turner's Syndrome, 45, X0/46, XY Karyotype: A case report.: Dong Wook Kang, Jin Man Kim, Kwang Sun Suh, Kyu Sang Song, Dae Yung Kang; Korean J Pathol. 1995;29(1):85-90.

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Abstract PDF: Turner's syndrome results from complete or partial monosomy of the X chromosome and is characterized by hypogonadism or related other congenital anomalies in phenotypic females. In these patients, there are failure to develop normal secondary sex characteristics, amenorrhea, or short stature at puberty and the ovaries are reduced to atrophic fibrous strands devoid of ova and follicles(streak gonads). Individuals with this condition are particularly prone to the development of gonadoblastoma. For this reason, the gonads should be early removed and supplemental estrogen therapy given. We experienced a case of Turner's syndrome, 45, XO/46, XY karyotype in a 20-year-old phenotypic female complained an amenorrhea. On the exploratory laparotomy, the right gonadal mass is sevearly adhered to the adjacent organs and measures 8 x 5 x 5 cm in dimension and 75gm in weight and shows multiple foci of hemorrhage with necrosis. The left streak gonad measures 3.5 x 2 x 1.5 cm in dimension and shows multiple foci of calcification. Microscopically, the right gonadal mass reveals malignant mixed germ cell tumor, composed of endodermal sinus tumor, composed of endodermal sinus tumor with dysgerminoma and gonadoblastoma. The left streak gonad consists of mainly dense fibrous connective tissue and shows some foci of calcification associated with gonadoblastoma. On immunohistochemical and special stainings, the cytoplasm and hyalin droplets of the endodermal sinus tumor component reveal strong positivity to the a-fetoprotein and PAS. After removal of both gonads, the serum level of the a-fetoprotein is markedly down from 1742ng/ml to 2.6 ng/ml.

Ileal anisakiasis: A report of two cases.: Young Ran Shim, Dong Sug Kim, Tae Sook Lee; Korean J Pathol. 1995;29(1):91-95.

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Abstract PDF: Anisakiasis is a parasitic disease of the gastrointestinal tract caused by ingestion Of raw or undercooked fish containing the marine nematode larvae belong to the subfamily Anisakinae. The adult worms are intestinal parasites of marine mammals. Eggs are passed in the feces of these mammals and develop to the second stage larvae in the sea water. They are eaten by crustaceans in which the larvae develop to the third stage. When fish or squid eat the infected crustaceans the larvae migrate to the body cavity or the muscle. The infected fish or squid is eaten by marine mammals the larvae attach to the wall of the stomach and then undergo adult worm. In Korea, human anisakiasis is not rare. The clinical manifestations are variable and depend on the involving site of gastrointestinal tract. The frequent sites are stomach and small intestine, and large intestine is rarely involved. Recently we experienced two cases of ileal anisakiasis occurred in 54-year-old female and 46-year-old female patients. The symptoms were upper and lower abdominal pain, nausea, and vomiting. The resected ileums in case I and 2 measured 12.5 x 2.5 cm and 15.0 x 2.0 cm, respectively. The mucosa and submucosa were thickened. In case 1, submucosal penetration of a white thread-like parasite was seen. The ileum showed submucosal edema, and extensive infiltration of eosinophils, neutrophils, lymphocytes, histiocytes, and plasma cells from mucosa to mesentery with or without mucosal ulceration. The Anisakis larvae are found in the submucosa and propria muscle. They have thick multilayered smooth cuticle, many somatic muscle cells, triradiated esophagus with numerous tall columnar cells, renette cell, and Y-shaped lateral chords. Reproductive organ is absent. In Korea, the previously reported 14 cases and present 2 cases of the intestinal anisakiasis mainly involved ileum, but the cause was not mentioned.

Fetal Rhabdomyomatous Nephroblastoma: A case report.: Nam Hoon Kim, Chan Pil Park, Eun Kyung Hong, Poong Man Jung, Moon Hyang Park; Korean J Pathol. 1995;29(1):96-102.

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Abstract PDF: A fetal rhabdomyomatous nephroblastoma is considered to be a predominantly monophasic mesenchymal variant of Wilms' tumor, which acts less aggressively than a conventional Wilms' tumor despite its much larger size. Bilaterality of this tumor in a nine month-old girl, however, may negatively affect the overall prognosis. A radical nephrectomy for bulky masses in the left kidney and a partial nephrectomy for right kidney with five small tumor masses was performed at the same time. Two small tumor masses in the upper part of right kidney were left behind because of preserving minimal renal functional capacity. Pathological study revealed a mixed type of nephroblastoma which was composed predominantly of mesenchymal components with fetal rhabdomyomatous differentiation. After post-operative chemotherapy with vincristine, actinomycin D and adriamycin, and radiotherapy(2,130 rad), residual tumor masses became a single tumor 5 cm in diameter and well demarcated, which was resected at 15 months after first operation when the size and renal function of remained right kidney was appropriate to resect out the residual tumor. The tumor resected out at second operation was entirely composed of scattered differentiated fetal skeletal muscle cells in the fibrovascular tissue. Only a few entrapped epithelial components were seen but no blastemal cornponents were present. Follow up abdominal CT and ultrasonographic examinations revealed no evidence of tumor recurrence. The girl has developed normally without disease.

Elastofibromatous Lesion of the Stomach: A case report.: Mee Sook Roh, Sook Hee Hong; Korean J Pathol. 1995;29(1):103-105.

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Abstract PDF: Elastofibroma is a peculiar tumor-like lesion which manifests as a slowly growing, solid, ill-defined mass of fibroelastic tissue occurring almost exclusively in elderly persons. It has been found in the ,,ubscapular region but rare examples have also been found in other locations. We experienced a case of elastofibromatous lesion of the stomach. The lesion was incidentally found in a 71 -year-old woman during an operation of cholecystectomy due to chronic cholecystitis and choledocholithiasis. The lesion was a relatively well-defined but not encapsulated small nodule, 0.7 cm in diameter, at submucosal layer of gastric pylorus. Histologically the nodular mass consisted of abundant acellular collagen fibers containing numerous elastofibroma fibers.

Holoprosencephaly Associated with 63, XXY Karyotype: An autopsy report.: Ji Hwa Kim, Ik Su Kim, Je Geun Chi; Korean J Pathol. 1995;29(1):106-109.

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Abstract PDF: Holoprosencephaly, a grave malformation during cleavage phase of brain development, occurs in association with a variety of clinical syndrome including chromosomal aberration. Among chromosomal anomalies trisomy syndromes, particularly trisomy 18, are often associated with holoprosencephaly. Triploidy with holoprosencephaly had also been described. We report an autopsy case of incomplete triploidy with abnormal sex chromosome, i.e., 63, XXY. Our case showed a marked intrauterine growth retardation, and postmortem examination revealed alobar holoprosencephaly, hypotelorism, bilateral cleft palates and lips, flat nose, microstomia, lowset ears, congenital heart disease and cystic kidney. The brain was microcephalic 5 x 6 cm and was of pancake shape. there was a large dorsal cyst. Olfactory tracts and bulbs were absent. The brain surface was smooth, and only suggestive hippocampal fissure was noted. The basal ganglia and thalami were fused in midline and the aqueductal origin was exposed. The brain stem and cerebellum were unremarkable. Repeated karyotypings revealed 63,XXY consistently. All 21 chromosomes showed trisomy except for D group. The sex chromosome was XXY, and the genital tract and gonad were those of female.

Glomus Tumor of the Stomach.: Anhi Lee; Korean J Pathol. 1995;29(1):110-112.

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Abstract PDF: The glomus tumor or glomangioma is an uncommon benign tumor that arises from the modified smooth muscle cells of the glomus body, a neuromyoarterial receptor sensitive to temperature, that regulates arterial flow. It is most commonly found in the skin particularly in the nailbeds or fingertips, but approximately 70 cases described in the stomach. The author experienced a glomus tumor of the stomach was found in a 43 year old female patient who had discomfort in upper abdomen for 40 days. Clinically, this uncommon gastric tumor mimics most of the benign and malignant lesions of the stomach and the most important aspect of this tumor is its histologic identification and differentiation from the more common gastric lesion. Microscopically the tumor was composed of cellular lobules of various sizes separately by irregular fibrous and muscular trabeculae. Ultrastructural study showed basal lamina, pinocytotic vesicles and numerous subplaomalemmal plaque.

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