Journal of Pathology and Translational Medicine

Original Article

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas: Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim; J Pathol Transl Med. 2022;56(1):22-31. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.31

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Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

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A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
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Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
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Case Studies

Amoebic Encephalitis Caused by Balamuthia mandrillaris: Su Jung Kum, Hye Won Lee, Hye Ra Jung, Misun Choe, Sang Pyo Kim; J Pathol Transl Med. 2019;53(5):327-331. Published online May 24, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.14

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Abstract PDF

We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.

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Ju Yeon Lee, In Kyu Yu, Seong Min Kim, Joo Heon Kim, Ha Youn Kim
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Lei Wang, Wenjing Cheng, Bing Li, Zhe Jian, Xianlong Qi, Dongjie Sun, Jian Gao, Xuetao Lu, Yi Yang, Kun Lin, Chuanlong Lu, Jiaxi Chen, Chunying Li, Gang Wang, Tianwen Gao
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Methotrexate/nonsteroidal anti-inflammatory drugs/steroids

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Monica M. Kangussu-Marcolino, Gretchen M. Ehrenkaufer, Emily Chen, Anjan Debnath, Upinder Singh
International Journal for Parasitology: Drugs and Drug Resistance.2019; 11: 80. CrossRef

Bile Granuloma Mimicking Peritoneal Seeding: A Case Report: Hasong Jeong, Hye Won Lee, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Yu Na Kang, Sang Pyo Kim, Misun Choe; J Pathol Transl Med. 2018;52(5):339-343. Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.06.02

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Abstract PDF

Laparoscopic cholecystectomy is a widely used treatment method for most cholelithiasis and is a relatively safe procedure. Foreign body granulomatous reaction to bile or gallstone spillage during laparoscopic cholecystectomy has rarely been reported. We report a case of bile granuloma after laparoscopic cholecystectomy, which mimicked peritoneal seeding. A 59-year-old Korean man presented with right upper quadrant pain. He underwent laparoscopic cholecystectomy for acute cholecystitis with cholelithiasis. Pathologic examination revealed an incidental adenocarcinoma invading the lamina propria with acute cholecystitis and cholelithiasis. After 3 months, follow-up abdominal computed tomography revealed a subhepatic nodule, which showed hypermetabolism on positron emission tomography–computed tomography. Suspecting localized peritoneal seeding, wedge resection of the liver, wedge resection of the transverse colon, and omentectomy were performed. Pathologic examination of the resected specimens revealed multiple bile granulomas. Awareness of bile granuloma mimicking malignancy is noteworthy for patient management to reduce unnecessary procedure during postoperative surveillance.

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SN Comprehensive Clinical Medicine.2023;[Epub] CrossRef
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Sajad Ahmad Salati, Mohammed Alfehaid, Saleh Alsuwaydani, Lamees AlSulaim
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Brief Case Report

A Primary Malignant Rhabdoid Tumor in Adult Liver: Yu Na Kang, Sang Pyo Kim, Byoung Kuk Jang; Korean J Pathol. 2013;47(5):486-488. Published online October 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.5.486

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Mesenchymal Tumors of the Liver: An Update Review
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Biomedicines.2025; 13(2): 479. CrossRef
Primary extrarenal rhabdoid tumour of the liver: a case report and literature review
M Meyers, P Demetter, A.K. De Roo, M Pezzullo, C Jungels, B Brichard, C De Magnee, R.R. De Krijger, G Verset
Acta Gastro Enterologica Belgica.2024; 86(4): 555. CrossRef
Malignant rhabdoid tumor of the liver in a middle-aged woman: a case report and literature review
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Embryonic signature distinguishes pediatric and adult rhabdoid tumors from other SMARCB1-deficient cancers
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Case Report

A Soft Tissue Perineurioma and a Hybrid Tumor of Perineurioma and Schwannoma: Ji Young Park, Nam Jo Park, Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee; Korean J Pathol. 2012;46(1):75-78. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.75

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Abstract PDF

Perineuriomas are composed of differentiated perineurial cells. Perineuriomas have been recently recognized by the immunoreactivity for epithelial membrane antigen (EMA). Microscopically, perineuriomas show proliferation of spindle cells with wavy nuclei and delicate elongated bipolar cytoplasmic processes. The tumor cells are usually negative for the S-100 protein. Ultrastructurally, perineurial cells reveal slender, nontapered processes containing pinocytic vesicles and discontinuous basal lamina. Interestingly, hybrid tumors of benign peripheral nerve sheath tumor (PNST) have been recently reported by using immunohistochemical and ultrastructural investigations. Herein, we report a case of soft tissue perineurioma arising in the skin of a 56-year-old female; another case of a hybrid tumor of perineurioma and schwannoma in the posterior mediastinum occurred in a 53-year-old male, which is the first case of the hybrid PNST tumor reported in Korea.

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Erika F. Rodriguez, Robert Jones, Daniel Miller, Fausto J. Rodriguez
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A Rare Perineurioma/Granular Cell Tumor Hybrid Peripheral Nerve Sheath Tumor
Koorosh Haghayeghi, Gladys Telang, Sonja Chen, Jack Bevivino, Shamlal Mangray, Yiang Hui, Leslie Robinson-Bostom
The American Journal of Dermatopathology.2020; 42(10): 762. CrossRef
Hybrid peripheral nerve sheath tumors
Emine KILIÇ BAĞIR, Arbil AÇIKALIN, Gülfiliz GÖNLÜŞEN, Suzan ZORLUDEMİR, Mehmet Ali DEVECİ
Cukurova Medical Journal.2019; 44(3): 804. CrossRef
Primary intraosseous hybrid epithelioid schwannoma/perineurioma in the proximal tibia: a case report of benign hybrid neoplasm with local hypercellularity
Yuejiao Lang, Dawei Liu, Pei Xiang, Jilin Wang, Yang Li
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Nasir Ud Din, Zubair Ahmad, Jamshid Abdul-Ghafar, Rashida Ahmed
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Louis Tsun Cheung Chow
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Michael A. den Bakker, Alexander Marx, Kiyoshi Mukai, Philipp Ströbel
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Original Articles

Prognostic Significance and Nature of Rhabdoid Features in Renal Cell Carcinoma.: Misun Choe, Ji Young Park, Ilseon Hwang, Sang Pyo Kim; Korean J Pathol. 2011;45(4):371-378.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.371

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Abstract PDF: BACKGROUND
Recent reports have indicated that renal cell carcinoma (RCC) with rhabdoid features follows an aggressive clinical course. We investigated the prognostic significance and nature of the rhabdoid component.
METHODS
We retrospectively analyzed the incidence and clinicopathologic characteristics of RCC with rhabdoid features in 174 radical nephrectomy cases. The specimens were examined histologically and immunohistochemically.
RESULTS
Twelve of the 174 RCC cases (6.9%) showed rhabdoid features. Histologically, all the tumors with rhabdoid features were of the clear cell type. The presence of rhabdoid features was significantly associated with higher Fuhrman's nuclear grade and higher pathologic tumor stage at presentation. Among the 12 patients who showed the rhabdoid component, nine (75%) developed metastasis and seven (58.3%) died of disease-related causes. The presence of rhabdoid features was independently associated with metastasis and disease-related mortality. The rhabdoid cells were positive for vimentin; variably positive for pan-cytokeratin, epithelial membrane antigen, and CD10; and negative for cytokeratin 7, smooth muscle actin, desmin, E-cadherin, and c-Kit. No case showed loss of integrase interactor-1; one was p53 positive, and five were insulin-like growth factor mRNA binding protein 3 positive. The Ki-67 labeling index was 1-25% (mean, 5.5%).
CONCLUSIONS
The rhabdoid component is an independent prognostic factor for metastasis of RCC; therefore, identification of this component is critical.

Comparative Study of Relative Value for Diagnostic Procedure of Surgical Pathology in Korea and United States.: Ilseon Hwang, Yu Na Kang, Kun Young Kwon, Sun Young Kwon, Sang Pyo Kim, Sang Sook Lee, Hye Ra Jung, Mi Sun Choe; Korean J Pathol. 2011;45(1):9-14.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.9

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Abstract PDF

BACKGROUND
Pathologic examination is a very important diagnostic procedure. It is the most important method to decide the therapeutic plan and to predict the prognosis of cancer patients. The Resource-Based Relative Value Scale (RBRVS) is a schema used to determine how much money medical providers should be paid. In Korea, a modified RBRVS has been used since the year 2000.
METHODS
We researched the July 2010 RBRVS for Korea and the US medicare. The individual Relative Evaluation Index (REI) is defined as the ratio of an individual RBRVS to the mean RBRVS. The REIs of pathologic examination in Korea and America were compared.
RESULTS
For an endoscopic biopsy specimen, the pathologic examination REI in Korea was 55.4% of the American REI. The Korean REI of a prostate biopsy (8 sites) was only 5.7% of the American REI. The Korean REI was 28.1% of the American REI for the hysterectomy for uterine myoma, and the Korean REI was 67.6% of the American REI for resection of stomach or colon cancer.
CONCLUSIONS
The RBRVS of pathologic examination in Korea remains undervalued. Considering the importance of pathologic examination in medicine, the RBRVS in Korea should be increased.

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Diminutive and Small Colorectal Polyps: The Pathologist's Perspective
Yun Kyung Kang
Clinical Endoscopy.2014; 47(5): 404. CrossRef
Early Colorectal Epithelial Neoplasm in Korea: A Multicenter Survey of Pathologic Diagnosis
Yun Kyung Kang, So-Young Jin, Mee Soo Chang, Jung Yeon Kim, Gyeong Hoon Kang, Hye Seung Lee, Jin Hee Sohn, Ho Sung Park, Kye Won Kwon, Mi Jin Gu, Young Hee Maeng, Jong Eun Joo, Haeng Ji Kang, Hee Kyung Kim, Kee-Taek Jang, Mi Ja Lee, Hee Kyung Chang, Joon
Korean Journal of Pathology.2013; 47(3): 245. CrossRef

Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.: Ji Min Jeon, Hye Won Lee, Ji Young Park, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Mi Sun Choe, Yu Na Kang, Sang Pyo Kim, Sang Sook Lee, Won Il Choi, Kun Young Kwon; Korean J Pathol. 2010;44(4):397-403.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.397

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Abstract PDF

BACKGROUND
Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance.
METHODS
We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray.
RESULTS
We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128).
CONCLUSIONS
MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.

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Case Report

Secretory Meningioma: Report of 2 cases.: Dong Sug Kim, Eun Hi Lee, Young Ran Shim, Sang Pyo Kim, Oh Ryong Kim; Korean J Pathol. 1995;29(3):361-367.

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Abstract PDF: The secretary meningioma is a distinct variant of meningioma that revealed characteristic light microscopic, immunohistochemical and ultrastructural features of epithelial and secretary differentiation, which was named as a distinct subtype of meningioma by Alguacil-Garcia et al in 1986. We experienced 2 cases of secretary meningioma. One was a 53-year-old female who had suffered from sudden onset of dizziness for I day. The computerized tomography revealed a sharply marginated well enhanced mass in temporal lobe. The other was a 59-year-old female who had suffered from dizziness for 8 years. The computerized tomography revealed a well demarcated lobulated mass in petrosal ridge. In both cases, multiple hyaline inclusions were scattered in the background of meningothelial meningioma. They were PAS positive, diastase resistant, stained yellow with van Gieson, and did not stain with reticulin in contrast to Psammoma bodies. The immunohistochemistry revealed positive reaction for EMA, CEA, a-FP and cytokeratin. T'he electron microscopic study revealed interdigitation with desmosomes and abundant intracellular lumina. They were lined by numerous microvilli and filled with granular material which was composed of electron dense homogenous material, me branous material, and small membrane-bound vesicles. Microvilli were filled with electron dense material identical to the material in the lumina, and some of them were interconnected with electron dense material in the lumina. It was concluded that secretary activity of the meningothelial cells and degenerated microvilli were involved in the pathogenesis of hyaline inclusions.

Original Article

Capillary Plexus and Vasa of the Rat Lung as Revealed by Scanning Electron Microscope of Corrosion Casts.: Kun Young Kwon, Kam Rae Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; Korean J Pathol. 1993;27(1):11-18.

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Abstract PDF: The pulmonary microvasculatures of rats were studied by injection replicas prepared from Mercox. This medium enabled us to easily obtain consistent, stable, and complete injected replicas of the pulmonary vasculature. In order to investigate the three dimensional structures of the tributaries of the bronchial artery, such as the capillary plexus and vasa vasorum, we performed a scanning electron microscopic(SEM) study of the vascular casts, using Mercox CL-2B as a media. The alveolar capillaries revealed hexagonal or pentagonal rings of vascular networks. In some areas, the vascular rings composed a square network, The bronchial tree was supplied by the bronchial arteries which form a coarse capillary extending as far as the terminal bronchioles. Occasionally the capillary plexus was connected with adjacent capillary networks in and around the alveolar walls. The walls of the pulmonary artery revealed only a single layer of the vasa vasorum, but those of the pulmonary vein were surrounded by more complicated and well developed vasa vasorum than the pulmonary arterial side. The mean diameters of the venous vasa vasorum are greater than the arterial vasa vasorum.

Case Reports

A Case of Pseudoinvasion in Peutz-Jeghers Polyposis.: Sang Pyo Kim, Sang Sook Lee, Eun Sook Chang; Korean J Pathol. 1993;27(1):72-74.

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Abstract PDF: Peutz-Jeghers polyp with pseudoinvasion is characterized by the presence of mucosal islands within muscle layer often associated with mucinous cysts. It occurs when mucosal components completely penetrate the muscularis propria, and shows no cytologic signs of malignancy. In most instances, the lesion may be the result of forces exerted during intussusception in the involved small intestine. We describe a case of Peutz-Jeghers polyposis with pseudoinvasion in a 24-year-old female patient. This patient presented with intussusception and a segmental resection of the ileum was performed. Microscopically, it disclosed a hamartomatous polyp with pseudoinvasion. There were glandular islands and mucinous cysts embedded within the bundle of muscle, layer, extending, to the subserosa. There was o evidence of cellular dysplasia or desmoplasia.

Metastatic Alveolar Soft Part Sarcoma Presented with a Dura Mass: A Case Report.: Sun Young Kwon, Hyun Chang Joo, Kun Young Kwon, Sang Sook Lee, Chul Ho Sohn, Man Bin Yim, Sang Pyo Kim; Korean J Pathol. 2001;35(2):180-183.

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Abstract PDF: Alveolar soft part sarcoma, accounting for less than 1% of all soft tissue sarcomas, is known for late metastases to the lung, bone and brain. We have examined a case of metastatic alveolar soft part sarcoma to the brain in a 34-year-old woman. Computed tomography of the brain revealed a well enhancing dura based mass of the left temporal area. The patient had a previous history of surgery for alveolar soft part sarcoma from the right thigh at the age of 24 years. She underwent total removal of the dural mass under the clinical impression of the meningioma. Grossly, a well-circumscribed, pale tan and solid mass was 3.4 x 3.2 x 2.4 cm and easily detached from the attached dura. Histologically, the tumor showed typical features of alveolar soft part sarcoma. Immunohistochemically, tumor cells were positive for muscle related antibodies. Ultrastructural examination showed rod-shaped membrane bound crystals and electron-dense granules in the cytoplasm of tumor cells.

Original Articles

Morphologic Changes of Pulmonary Tissue Secondary to Sidestream Cigarette Smoke.: Kun Young Kwon, Ji Min Jeon, Sang Pyo Kim, Kwan Kyu Park, Dae Hyun Kim; Korean J Pathol. 1999;33(6):395-403.

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Abstract PDF: Chronic bronchiolitis is a condition associated with cigarette smoking, and later associated with pulmonary parenchymal alteration and progressive deterioration of lung function. Early respiratory bronchiolitis was produced in Sprague-Dawley rats by indirect inhalation of cigarette smoke daily in a smoke exposure chamber designed by authors for 1 month. Experimental group A (n=5) was sacrificed after having smoked 30 cigarettes, group B (n=5) after 80 cigarette, and group C (n=7) after 140 cigarettes, respectively. Examination of morphologic changes in the lungs was done on light microscope, transmission and scanning electron microscopes. Light microscopically, increase in number of goblet cells in the bronchial mucosa, brown-pigmented macrophages in the alveoli, multifocal alveolar collapse adjacent to the bronchioles, dilatation of alveolar ducts and alveolar spaces were observed. Transmission electron microscopically, irregularly shaped Clara cells, alveolar wall collapse, and focally type I epithelial cell injury were seen. Scanning electron microscopically, scattered alveolar collapse, irregular dilatation of alveolar ducts, alveolar spaces and interalveolar pores (pores of Kohn) were seen. The terminal and respiratory bronchioles showed morphological alteration of Clara cells, but no evidence of cellular bronchiolitis or bronchiolar obstruction. We conclude that sidestream smoke induces an early respiratory bronchiolitis including aggregates of brown pigmented macrophages and varying degrees of structural alteration of adjacent pulmonary parenchyma.

Fine needle aspiration cytology of endodermal sinus tumor of the mediastinum.: Kam Rae Cho, Sang Pyo Kim, Kwan Kyu Park, Kun Young Kwon, Eun Sook Chang; J Pathol Transl Med. 1993;4(1):57-61.

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Abstract PDF: No abstract available.

Apoptosis of Alveolar Cells in Pneumocystis Carinii Pneumonia: Application of Electron Microscopic Terminal Deoxynucleotidyl Transferase-Mediated dUTP-Biotin Nick End Labeling Method.: Kyu Hun Kang, Sang Pyo Kim, Kun Young Kwon; Korean J Pathol. 2001;35(6):496-505.

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Abstract: BACKGROUND
Pneumocystis carinii (P. carinii) attaches to alveolar cells and causes injury to the epithelial cells by direct toxic effects or inhibition of epithelial growth and replication. Although respiratory cell damage or death is a common feature in P. carinii pneumonia, there has been little reports about expression of apoptosis of the lung tissue in the literatures.
METHODS
We examined expression of fibronectin and vitronectin in the interaction between P. carinii and alveolar cells, and in situ terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) expression of apoptosis in the respiratory cells by immunohistochemistry and pre-embedding immunoelectron microscopy.
RESULTS
Light microscopic (LM) and electron microscopic (EM) immunohistochemical stains for the fibronectin and vitronectin showed strong expressions on the pellicles and tubular extensions of P. carinii and weak expression along the surfaces of type I alveolar cells. LM and EM TUNEL stains showed positive expression in the nuclei of alveolar cells, apoptotic bodies in the cytoplasm of alveolar macrophages and cellular debris in alveolar spaces.
CONCLUSIONS
P. carinii induces injury and apoptosis of alveolar cells after attachment of the organisms to host cells, and alveolar macrophages enhance the clearance of apoptotic bodies of alveolar cells as well as phagocytosis and degradation of P. carinii.

Pathologic Analysis of 71 Cases of Cerebral Cortical Dysplasia.: Sang Pyo Kim, Seung Che Cho; Korean J Pathol. 1997;31(9):815-822.

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Abstract PDF: Cortical dysplasia (CD) is considered to be a malformative lesion of the neocortex which exhibits a spectrum of pathologic changes reflecting a disturbance in the process of its development. CD is recently recognized as a major cause of intractable epilepsy with non-neoplastic lesions. Mischel et al. proposed that CD can be graded mild, moderate and severe with regard to nine specific microscopic abnormalities: mild CD consists of 1) cortical laminar disorganization, 2) single heterotopic white matter neurons, 3) neurons in the cortical molecular layer, 4) persistent remnants of the subpial granular cell layer, and 5) marginal glioneuronal heterotopia; moderate CD displays 6) polymicrogyria and 7) white matter neuronal heterotopia; severe CD phows 8) neuronal cytomegaly with associated cytoskeletal abnormalities and 9) balloon cell change. We reassessed 71 cases of cortical dysplasia to elucidate the proportion and histologic features of each group, using Mischel's grading system. CD was most frequently found in the temporal lobe with 50 cases (70%). Mild CD was predominently seen and was noted in 61 cases (86%) Cortical laminar disorganization and single heterotopic white matter neurons were identified in all mild CD cases. Neurons in the cortical molecular layer, persistent subpial granular cell layer, and marginal glioneuronal heterotopia were also noted in case numbers 40, 3, and 1 of mild CD, respectively. Moderate CD was composed of 2 cases with polymicrogyria, and the remaining 8 cases had severe CD. All moderate and severe CD were associated with the various histological features of mild CD. Thirty eight cases (51%) of CD showed dual pathology, composed of both CD and hippocampal sclerosis, and 5 cases of dysembryoplastic neuroepithelial tumor also had CD. Neurofilament immunostain revealed disarray of abnormally beaded axons in CD. We believe that the grading system of CD is very important to the evaluation and classification of CD.

Bronchoalveolar Lavage of Pneumocystis carinii Pneumonia: Cytological and Ultrastructural Features.: Kun Young Kwon, Cheol Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; J Pathol Transl Med. 1994;5(1):1-9.

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Abstract PDF: The cytological and ultrastructural findings of Pneumocystis carinii(PC) obtained from rats by bronchoalveolar lavage(BAL) are described. All developmental forms of the PC organisms were obtained in the lavage fluid. Ultrastructurally, the cysts were almost circular in shape, and were nearly devoid of surface tubular extensions. The wall of the cyst was composed of an unit membrane, and intermediate electron lucent layer and an external electron dense layer. The cysts frequently contained intracystic bodies, so called sporozoites. Occasionally empty or collapsed cysts with no intracystic bodies, and precysts were found. Trophozoites were variable in size and shape with abundant tubular extensions along the single electron dense pellicle. BAL is a useful method for concentrating the various morphologic forms of PC organisms, and is a rapid diagnostic method for PC pneumonia.

Sertoli-Leydig Cell Tumor with a Coexisting Brenner Tumor of the Ovary.: Ji Youn Bae, Sang Pyo Kim, Kwan Kyu Park, Soon Do Cha; Korean J Pathol. 1996;30(3):266-268.

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Abstract PDF: Sertoli-Leydig cell tumor or Brenner tumor is a relatively rare ovarian tumor. Other associated elements in the form of epithelial, mesenchymal, and tumor components of each tumor have been reported. The Sertoli-Leydig cell tumor with a Brenner tumor element has not been documented in the literature, so we are reporting on a case of Sertoli-Leydig cell tumor coexisting with a Brenner tumor. This 62-year-old woman presented with a 4 year history of lower abdominal mass and vaginal bleeding. Exploratory laparotomy was done. The left ovary showed a multiseptated, cystic, yellow-white solid mass, measuring 17.0x13.0x5.0 cm and weighing 985.0 gm. Microscopic examination revealed a tubular or trabecular arrangement of the Sertoli cells and variable numbers of Leydig cells. There were several tumor nests with cystic spaces composed of ovoid cells showing longitudinal nuclear grooving. Sarcomatoid or heterologous elements were not found.

Non-neoplastic Lesions in Temporal Lobe Epilepsy: A Pathologic Review of 64 cases.: Sang Pyo Kim, Kun Young Kwon, Eun Sook Chang, Kwan Kyu Park, Sang Do Yi, Eun Ik Son; Korean J Pathol. 1996;30(4):281-292.

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Abstract PDF: Temporal lobe epilepsy is characterized by complex partial seizures with either primary intracranial neoplasms or other non-neoplastic lesions. We reviewed 64 cases of surgically resected temporal lobes and amygdalo-hippocampal regions for temporal lobe epilepsy ansed by non-neoplastic lesions to elucidate the incidence and histologic features of each histologic group for a period of 2 years. The patient's age ranged from 12 to 49 years and the ratio of male to female was 42:22. There were 37 cases(57.8%) with single pathology and an additional 20 cases(31.3%) with dual pathology. The emaining 7 cases(10.9%) had no structural alternations. The most common temporal lobe pathology was hippocampal sclerosis in 41 cases(64.1%), diagnosed alone in 21 cases and as dual lesions in 20 cases. The hippocampal neuron loss was most pro,omemt in CA1, followed by CA4, CA3, and CA2. Amygdaloid sclerosis was present in 28 cases(43.8%), lases had 13 dual lesions, 25 cases also had hippocampal sclerosis. The 20 dual lesions showed that 6 cortical dysplasia, 10 microdysgenesis, 1 chronic non-specific inflammatory lesion, and 3 cysticercosis were associated with the various degree of mesial temporal sclerosis. Neuronoglial malformative lesions were identified in 21 cases(32.8%) including 16 dual lesion cases, which composed of 15 microdysgenesis and 6 cortical dysplasia. Neurofilament immunostain for cortical dysplasia revealed abnormally beaded disarray of axons in dysplastic pyramidal cells. The remaining pathologic lesions observed were 1 cysticercosis, 1 chronic non-specific inflammatory lesion, 3 arteriovenous malformation, 2 fibrous nodule, and 1 fibrous adhesions of the arachnoid.

Cytologic Findings of Giant Cell Carcinoma of the Lung.: Cheol Hee Yun, Ji Yeon Bae, Sang Pyo Kim, Kun Young Kwon, Chung Sook Kim, Eun Sook Chang; J Pathol Transl Med. 1994;5(2):154-159.

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Abstract PDF: Pulmonary giant cell carcinoma is one of the most highly malignant neoplasms of the lung. Although mixed malignant glandular or squamous components may be associated with a giant cell carcinoma, it is a distinct clinical and morphologic entity. We reviewed cytologic presentations of 6 cases of pulmonary giant cell carcinoma. Cytologically, the single most characteristic feature of giant cell carcinoma was an extremely large, bizarre cancer cell engulfing numerous leukocytes. The nuclei of these cells showed occasional prominent nucleoli, and the cytoplasm was abundant. Giant cells were also seen in other types of pulmonary carcinoma, but the giant cells of this neoplasm could be differentiated from those encountered in undifferentiated large cell carcinoma and squamous cell carcinoma by the abundant cytoplasm, the presence of markedly enlarged nuclei, prominent nucleoli, and an significant degree of phagocytosis, In conclusion, precise diagnosis and classification of lung cancer is imperative because of proved correlation between cell type and prognosis.

Multiple Primary Malignant Tumors: 39 cases.: Sun Young Kim, Sang Pyo Kim, Jong Min Chae, Sang Sook Lee, Eun Sook Chang, Chai Hong Chung; Korean J Pathol. 1987;21(2):67-74.

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Abstract PDF: Thirty nine cases of multiple primary malignant tumors examined at the Department of Pathology, Keimyung University School of Medicine during the period from November 1974 through March 1986 were analysed clinicopathologically. The findings are as follows: 1) Thirty nine cases had synchronous lesion and six cases metachronous lesion. The second primary malignancy occurred mean 4.7 years after the first malignancy in patients with metachronous lesion. 2) The age at diagnosis of the first malignancy ranged from 26 to 76 years, the average being 51.8 years. The male-female ratio was slightly less than 1:1.2. 3) The most commonly involved site in multicentric origin was gastrointestinal tract (44.4%) with all adenocarcinoma and the second urogenital system (29.6%). In cases of different tissues or organs (11 cases), ovary was the most frequent site (5 cases), followed by cervix (4 cases). 4) Multiple primary malignant tumors of urogenital system were all eight cases and six cases among them (75%) had smoking and drinking habits. 5) The detailed informations about possible environmental, familial and host factors necessary for the investigation of multiple primary tumors were lacking in most cases. Therefore, the history taking with special attention to these factors must be carefully recorded. And also, we suggest that in the high-risk individuals, careful follow-up and thorough search for early cancer detection or prevention should be taken.

Case Report

Fine Needle Aspiration Cytology of Invasive Micropapillary Carcinoma of the Breast: Report of four Cases.: Sun Young Kwon, Hae Ra Jung, Yu Na Kang, Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee; J Pathol Transl Med. 2004;15(2):106-111.

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Abstract PDF: Invasive micropapillary carcinoma (IMPCa) is a rare variant of invasive ductal carcinoma of the breast. This variant is associated with a set of peculiar cytological findings and aggressive biological behaviors. In most reported cases, IMPCa has involved massive axillary lymph node metastases at the time of diagnosis. We experienced four cases of cytological features of IMPCa, all of which were verified by histological examination. Fine needle aspiration cytology (FNAC) revealed malignant epithelial cells, which formed small, oval to angulated papillary clusters, which lacked central fibrovascular cores. The histological findings of the four cases revealed both pure and mixed forms of IMPCa, composed of cohesive malignant epithelial cells, surrounded by distinctive clear spaces and separated by thin fibrous septa. All patients evidenced axillary lymph node metastases at the time of diagnosis. It is important to identify the peculiar cytological findings which would differentiate IMPCa from other diseases.

Original Articles

Cytokine Expression on Microglial Proliferation and Apoptosis in Rat Lumbar Spinal Cord Following Unilateral Sciatic Nerve Transection.: Sang Pyo Kim, Seung Il Suh, Young Rok Cho, Seung Che Cho, Seung Pil Kim, Jong Wook Park, Jyung Sik Kwak; Korean J Pathol. 1998;32(2):94-103.

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Abstract PDF: This study was carried out to elucidate the cytokine mRNAs expression and morphological features according to a microglial proliferation and apoptosis in a rat lumbar spinal cord, after a right sciatic nerve transection. The control group was composed of 5 rats (Spraque-Dawley) and the experimental group was composed of 70 rats. On post operation day (pod) 1, 2, 3, 5, and 7 eight rats were sacrificed on those days. On pod 10 five rats were sacrificed as well as five rats sacrificed on post operation weeks 2, 3, 4, 5, and 6. On light microscopy, activated microglia were often found in a perineuronal position around motoneurons in the ventral gray matter and more randomly distributed throughout the neuropil in the dorsal gray matter of lumbar spinal cord. GSA I-B4-positive microglia began to increase from 1 day after transection, and reached peak at 2~3 days and it persisted at 5~7 days and decreased thereafter. TUNEL-positive microglia was not observed in control group and began to increase from 5 days after transection and increased gradually until 3 weeks and decreased thereafter. On in situ RT-PCR, the positive signal for IL-1alpha and IL-6 mRNA was found mainly in the cytoplasm of the activated microglia and astrocytes at 1 day after transection and showed stronger signal at 3 days and decreased gradually until 10 days. TNF-alpha mRNA was detected 1 day after transection and remained for 7 days and localized to activated microglia as well as probably some astrocytes. The signal intensity of IL-1alpha and IL-6 mRNA was generally stronger than TNF-alpha mRNA. On transmission electron microscopy, there were chromatin condensation with margination toward nuclear membrane and condensation of cytoplasm at 3 days after transection. Apoptotic bodies were found after 5 days and increased gradually until 3 weeks. According to the above findings, it is concluded that apoptosis appears to be one mechanism by which activated microglia are gradually eliminated and cytokine expression seems to played an active role in the microglial turnover.

Cytologic Analysis of Malignant Effusion.: Sang Pyo Kim, Ji Yeon Bae, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Chung Sook Kim; J Pathol Transl Med. 1995;6(2):116-124.

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Abstract PDF: Eighty cases of malignant effusion were cytologically studied to elucidate the incidence of primary tumor site and cytologic characteristics of each tumor types. Eighty fluid specimens were composed of 43 ascitic, 35 pleural, and 2 pericardial effusion and primary tumor site had been confirmed by histology. The frequent primary sites were stomach (22 cases, 28%), lung (21 cases, 26%), ovary (11 cases, 14%), liver (7 cases, 9%), and breast (4 cases, 5%). The principal malignant tumors were adenocarcinoma (56 cases, 70%), squamous cell carcinoma (7 cases, 9%), liver cell carcinoma (7 cases, 9%), small cell carcinoma (4 cases, 5%), and non-Hodgkin}s lymphoma (4 cases, 5%). The distinctive cytologic findings according to primary tumor types were as follows ; the gastric adenocarcinomas were mainly characterized by isolated cells and irregular clusters sometimes with signet ring cells. Papillary serous cystadenocarcinoma of ovary showed frequently papillary clusters and occasional psammoma bodies. Breast carcinoma of ductal type showed cell balls with smooth margins. Colonic adenocarcinoma showed rather irregular clusters or palisading pattern of cylindrical cells. Metastatic squamous cell carcinoma, liver cell carcinoma, small cell carcinoma, and non-Hodgkin}s lymphoma showed also characteristic features. These findings indicate that the cytological features observed in the great majority of malignant effusion are similar to those of primary tumor types, which are very helpful to indentify the primary tumor site.

Alterations of 9p21-22 Region Encoding Genes in Primary Glioblastomas.: Hong Jik Doh, Seong Il Suh, Dong Won Kim, Il Man Kim, Man Bin Yim, Eun Ik Son, Kun Young Kwon, Sang Sook Lee, Sang Pyo Kim; Korean J Pathol. 2002;36(6):394-399.

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Abstract PDF: BACKGROUND
Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis.
METHODS
We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR.
RESULTS
Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas. The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found.
CONCLUSIONS
These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.

Overexpression of Mutant p53 in Human Anaplastic Astrocytoma and Glioblastoma Multiforme.: Sang Sook Lee, Kam Rae Cho, Cheoul Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Eun Ik Sohn; Korean J Pathol. 1994;28(4):376-380.

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Abstract PDF: A total of 30 cases of cerebral gliomas, including 6 cases of low grade astrocytomas, 6 anaplasticastrocytoomas and l8 glioblastomas multiforme, was examined immunohistochemically to demonstrate the overexpression of mutant forms of p53 protein and to evaluate their relationships with histological subtypes. A p53 monoclonal antibody was applied to the routine formalin fixed, paraffin-embedded tissues for this study using microwave-assisted avidin-biotin method. Overexpression of p53 protein was identified in 4 out of 6 anaplastic astrocytomas (66.7%) and in l3 out of l8 glioblastomas multiforme (72.2%). No immunohistochemical positivity of p53 was found in adjacent normal brain tissue, gliosis and 6 cases of astrocytoma. These results suggest that overexpression of mutant p53 may be an important step in the development and progression of malignant astrocytoma, especially of the aggressive subtypes of glioma, including glioblastoma multiforme.

Synaptic Reorganization of Dentate Mossy Fibers and Expression of Calcium Binding Proteins in Hippocampal Sclerosis of Temporal Lobe Epilepsy.: Sang Pyo Kim, Seung Pil Kim, Seung Che Cho, Young Rok Cho, Ji Min Jeon, Yu Na Kang, Kun Young Kwon, Eun Sook Chang; Korean J Pathol. 1998;32(5):328-336.

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Abstract: This study was designed to identify expression of calcium-binding proteins and synaptic reorganizations of dentate mossy fibers in hippocampal sclerosis of human temporal lobe epilepsy. Hippocampal neuronal density was quantitively analyzed in temporal lobe epilepsy group (n=50) to investigate the degree of hippocampal sclerosis and it was compared with that of autopsy control (n=3). To verify the distribution of calcium-binding proteins in neurons of epileptic hippocampi, the parvalbumin (PV)-immunoreactive and calbindin-D28K (CB)-immunoreactive neurons were quantitively analyzed in each area of Ammon's horn by immunohistochemical stain. Also, to clarify synaptic reorganizations of the dentate mossy fibers, a part of each hippocampus was examined under light microscopy and transmission electron microscopy using Timm sulphide silver method. In epileptic hippocampi, severity of hippocampal sclerosis (HS) was graded four, which consisted of 3 cases with no HS, 6 mild HS, 12 moderate HS, and 29 severe HS. The hippocampal neuronal loss was most prominent in CA1, followed by CA4 and CA2. Expression of calcium-binding proteins was more prevalent in CA2 of all groups. The proportion of PV-immunoreactive neurons in CA1 and CA4 significantly increased in the moderate and severe HS group, whereas the proportion of CB-immunoreactive neurons did not correlated with the severity of HS. Timm granules were noted in inner molecular supragranular layer of dentate gyrus of epileptic hippocampi and they tended to increase in proportion along with the severity of hippocampal sclerosis. Transmission electron microscopy showed that supragranular Timm granules corresponded to synaptic terminals of mossy fibers. These results suggest that parvalbumin appears to have more protective effect against neuronal loss and that mossy fiber synaptic reorganization seems to play a major role in pathogenesis of hippocampal sclerosis of human temporal lobe epilepsy.

Case Report

Congenital Cytomegalic Inclusion Disease combined with Hydrocephalus: A case report.: Kam Rae Cho, Cheol Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Taek Hoon Kim; Korean J Pathol. 1994;28(4):439-441.

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Abstract PDF: This is an autopsy-verifed case of the generalized cytomegalic inclusion disease occuring in a male fetus of a weeks gestation. The fetus revealed hydrocephalus and focal necrosis of brain, focal subcapsular necrosis of liver, and the typical cytomegalic inclusion cells having large acidophilic intranuclear inclusions in the liver, brain, kidney, lung, adrenal gland, pancreas and chorionic villi. Prominent extramedullary hematopoiesis was noted in the liver and kidney. Immuohistochemical staining using anti-cytomegalovirus antibody revealed intranuclear or occasionally intracytoplasmic immunoreactivity in brain, liver, pancreas, lung, kidney, and intestine.

Original Articles

Expression of Antigenic Surface Molecules of Pneumocystis Carinii by Immunoelectron Microscopic Examination.: Kun Young Kwon, Seung Che Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang; Korean J Pathol. 1998;32(6):393-403.

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Abstract: This study was carried out to investigate the morphologic characteristics and localization of antigenic molecules of Pneumocystis carinii in experimentally induced P. carinii pneumonia in rats. After six weeks of administration of low protein diet and dexamethasone, Sprague-Dawley rats were sacrificed to submit lungs or bronchoalveolar lavage for the study. Monoclonal (092, 900, 902, and 904) and polyclonal (SP-D) antibodies were used for immunohistochemistry and immunoelectron microscopy (ITEM and ISEM). Immunohistochemically P. carinii organisms were well identified as clusters or separated forms in the alveolar spaces being frequently attached to the alveolar walls. Immunoelectron microscopically the adherences of gold particles were observed on the surface of all stages of the P. carinii. Occasionally positive immunogold labeling was observed in the cytoplasm of the trophozoites and on the pellicle of the intracystic bodies within the cysts. The monoclonal antibodies 092, 900, 902, and 904 reacted mainly with pellicles of P. carinii, whereas SP-D labeled on the pellicles, intracystic bodies, cytoplasms of the alveolar macrophages, and free floated surfactant material in the alveolar spaces. The immunogold particles were observed more diffusely and intensely in the cysts than in the trophozoites. These results indicate that antigen is mainly localized on the pellicles, and accumulated during development from the trophozoite to the cyst stages.

Immunocytochemical Detection of Pneumocystis Carinii in Bronchoalveolar Lavage .: Kun Young Kwon, Seung Che Cho, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Chung Sook Kim; J Pathol Transl Med. 1997;8(1):27-34.

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Abstract PDF: Pneumocystis carinii is an established cause of pulmonary infections in immuno- compromised hosts. Several cytological stains, such as Papanicolaou, Gomori methenamine silver(GMS) and Diff-Quik have been used for detection of the organism, but occasionally can be laborious and, due to a degree of nonspecificity, may be misleading. We evaluated the diagnostic utility of immunocytochemical stains that recognize P. carinii in bronchoalveolar lavage from experimentally induced P. carinii pneumonia rats(n=15). In addition to routine stains for diagnosis by morphologic recognition of P. carinii on Papanicolaou, GMS and Diff-Quik stains, bronchoalveolar lavage samples were reacted with immunocytochemical stains using monoclonal antibodies(MAB) 092 and 902. In bronchoalveolar lavage P. carinii organisms were detected in 9 of 10 cases (90%) using each MAB 092 and 902, whereas GMS and Diff-Quik stains demonstrated P. carinii in 13(86%) and 11(73%) of 15 cases respectively. In lung tissue specimens(n=15) P. carinii organisms were well identified on GMS stain and immunohistochemical stains using MAB 092 and 902 in all cases. We believe that the immunocytochemical staining using MAB 092 and/or 902 is a very useful and diagnostic tool in addition to GMS and Diff-Quik stain to detect P. carinii organisms in bronchoalveolar lavage.

Mechanisms of Acinar Cell Deletion in Rat Pancreas Following Experimental Duct Ligation.: Sang Pyo Kim, Kun Young Kwon, Sang Sook Lee, Chai Hong Chung; Korean J Pathol. 1989;23(1):51-64.

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Abstract PDF: This study was carried out to investigate the mechanisms of acinar cell deletion, leading to the pancreatic atrophy of rat pancreas after experimental duct ligation. Fifty-seven male Sprague-Dawley rats, maintained on a stock diet, weighing 200 gm, in average, were divided into 2 experimental groups. Group 1. Control group. Six rats. Abdominal cavity was opened and closed without further treatment. Group 2. Fifty-one rats. Animals were treated with partial ligation of the pancratic ducts according to the procedure developed by Hultquist followed by sequential sacrifices at: 1 hour (3 rats), 3 hours (3 rats), 6 hours (6 rast), 12 hours (3 rats) and 24 hours (8 rats); 2 days (8 rats), 3 days (3 rats), 4 days (3 rats) and 5 days (5 rats); 1 week (3 rats), 2 weeks (3 rats) and 8 weeks (3 rats); after partial ligation was extirpated and examined by both light and electron microscopy. The results obtained were as follows: Light microscopically, noted were an interstitial edema and focal necrosis of the pancreatic tissue along with fine vacuolization and depletion of the zymogen granules in the acinar cell cytoplasms and condensation of the acinar cell nucleus. These changes were observed by 2 days after ligation. At about the same time, one can observe the dense body, identified to be apoptotic body, in the acinar cell which were found to be decreased in quantity. By 5 days after ligation, no recognizable acinar cells left in the collagenous stroma except intercalated ducts. Conspicuous stroma except intercalated ducts. Conspicuous stromal hyalinization, thereafter. Electron microscopically (TEM and SEM), nuclear condensation and margination toward the nuclear membrane was noted by 6 hours after duct ligation. By 24 hors sporadic membrane-bounded apoptotic bodies appeared in the acinar cells, the number of which reaching to the peak by 3 days after ligation. These apoptotic bodies were found to be phagocytosed by either intraepithelial mononuclear phagocytes or adjoining acinar cells. It can be concluded, therefore: That orderly remodeling of pancreatic exocrine tissue during atrophy is effected by rapid deletion of acinar cells by apoptosis.

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