Journal of Pathology and Translational Medicine

Review

Guideline Recommendations for Testing of ALK Gene Rearrangement in Lung Cancer: A Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyojin Kim, Hyo Sup Shim, Lucia Kim, Tae-Jung Kim, Kun Young Kwon, Geon Kook Lee, Jin-Haeng Chung; Korean J Pathol. 2014;48(1):1-9. Published online February 25, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.1.1

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Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Citations

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Gabriele Gamerith, Marcel Kloppenburg, Finn Mildner, Arno Amann, Sabine Merkelbach-Bruse, Carina Heydt, Janna Siemanowski, Reinhard Buettner, Michael Fiegl, Claudia Manzl, Georg Pall
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ALK Translocation in ALK-Positive Mesenchymal Tumors: Diagnostic and Therapeutic Insights
Minsun Jung, Kyung Chul Moon, Jeongmo Bae, Tae Min Kim, Miso Kim, Yoon Kyung Jeon, Cheol Lee
Archives of Pathology & Laboratory Medicine.2022; 146(12): 1460. CrossRef
Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
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Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets
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Lung Cancer.2019; 136: 65. CrossRef
Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric H. Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benj
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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors
Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric H. Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benj
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Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the
Neal I. Lindeman, Philip T. Cagle, Dara L. Aisner, Maria E. Arcila, Mary Beth Beasley, Eric H Bernicker, Carol Colasacco, Sanja Dacic, Fred R. Hirsch, Keith Kerr, David J. Kwiatkowski, Marc Ladanyi, Jan A. Nowak, Lynette Sholl, Robyn Temple-Smolkin, Benja
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5′/ 3′ imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer
Yongqing Tong, Zhijun Zhao, Bei Liu, Anyu Bao, Hongyun Zheng, Jian Gu, Mary McGrath, Ying Xia, Bihua Tan, Chunhua Song, Yan Li
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Molecular testing and treatment patterns for patients with advanced non-small cell lung cancer: PIvOTAL observational study
Dae Ho Lee, Ming-Sound Tsao, Karl-Otto Kambartel, Hiroshi Isobe, Ming-Shyan Huang, Carlos H. Barrios, Adnan Khattak, Filippo de Marinis, Smita Kothari, Ashwini Arunachalam, Xiting Cao, Thomas Burke, Amparo Valladares, Javier de Castro, Aamir Ahmad
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Microfluidics-based immunofluorescence for fast staining of ALK in lung adenocarcinoma
Saška Brajkovic, Benjamin Pelz, Maria-Giuseppina Procopio, Anne-Laure Leblond, Grégoire Repond, Ariane Schaub-Clerigué, Diego G Dupouy, Alex Soltermann
Diagnostic Pathology.2018;[Epub] CrossRef
Expanded Circulating Tumor Cells from a Patient with ALK- Positive Lung Cancer Present with EML4-ALK Rearrangement Along with Resistance Mutation and Enable Drug Sensitivity Testing: A Case Study
Zhuo Zhang, Hiroe Shiratsuchi, Nallasivam Palanisamy, Sunitha Nagrath, Nithya Ramnath
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Molecular Testing of Lung Cancers
Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee
Journal of Pathology and Translational Medicine.2017; 51(3): 242. CrossRef
Novel ALK fusion partners in lung cancer
Aglaya G. Iyevleva, Grigory A. Raskin, Vladislav I. Tiurin, Anna P. Sokolenko, Natalia V. Mitiushkina, Svetlana N. Aleksakhina, Aigul R. Garifullina, Tatiana N. Strelkova, Valery O. Merkulov, Alexandr O. Ivantsov, Ekatherina Sh. Kuligina, Kazimir M. Pozha
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Strategic management of transthoracic needle aspirates for histological subtyping and EGFR testing in patients with peripheral lung cancer: An institutional experience
Choonhee Son, Eun‐Ju Kang, Mee Sook Roh
Diagnostic Cytopathology.2015; 43(7): 532. CrossRef
Current and future molecular diagnostics in non-small-cell lung cancer
Chun Man Li, Wing Ying Chu, Di Lun Wong, Hin Fung Tsang, Nancy Bo Yin Tsui, Charles Ming Lok Chan, Vivian Wei Wen Xue, Parco Ming Fai Siu, Benjamin Yat Ming Yung, Lawrence Wing Chi Chan, Sze Chuen Cesar Wong
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Role of biopsy sampling for diagnosis of early and progressed hepatocellular carcinoma
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Molecular Pathology of Lung Cancer: Current Status and Future Directions
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Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements in lung cancer with nodular ground-glass opacity
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BMC Cancer.2014;[Epub] CrossRef

Original Article

No Detection of Simian Virus 40 in Malignant Mesothelioma in Korea: Minseob Eom, Jamshid Abdul-Ghafar, Sun-Mi Park, Joung Ho Han, Soon Won Hong, Kun Young Kwon, Eun Suk Ko, Lucia Kim, Wan Seop Kim, Seung Yeon Ha, Kyo Young Lee, Chang Hun Lee, Hye Kyoung Yoon, Yoo Duk Choi, Myoung Ja Chung, Soon-Hee Jung; Korean J Pathol. 2013;47(2):124-129. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.124

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Abstract PDF

Background

Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA.

Methods

We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA.

Results

Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls.

Conclusions

SV40 is not associated with the development of MM in Korea.

Citations

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Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China
Ru-ai Liu, Bo-yong Wang, Xin Chen, Yuan-qian Pu, Jia-ji Zi, Wen Mei, Ye-pin Zhang, Lu Qiu, Wei Xiong
Genetic Testing and Molecular Biomarkers.2024;[Epub] CrossRef
Binding of SV40’s Viral Capsid Protein VP1 to Its Glycosphingolipid Receptor GM1 Induces Negative Membrane Curvature: A Molecular Dynamics Study
Raisa Kociurzynski, Sophie D. Beck, Jean-Baptiste Bouhon, Winfried Römer, Volker Knecht
Langmuir.2019; 35(9): 3534. CrossRef
Estimated future incidence of malignant mesothelioma in South Korea: Projection from 2014 to 2033
Kyeong Min Kwak, Domyung Paek, Seung-sik Hwang, Young-Su Ju, Mark Allen Pershouse
PLOS ONE.2017; 12(8): e0183404. CrossRef
The function, mechanisms, and role of the genes PTEN and TP53 and the effects of asbestos in the development of malignant mesothelioma: a review focused on the genes' molecular mechanisms
Leonardo Vinícius Monteiro de Assis, Mauro César Isoldi
Tumor Biology.2014; 35(2): 889. CrossRef
The role of key genes and pathways involved in the tumorigenesis of Malignant Mesothelioma
Leonardo Vinícius Monteiro de Assis, Jamille Locatelli, Mauro César Isoldi
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2014; 1845(2): 232. CrossRef
Pleural Mesothelioma: An Institutional Experience of 66 Cases
Soomin Ahn, In Ho Choi, Joungho Han, Jhingook Kim, Myung-Ju Ahn
Korean Journal of Pathology.2014; 48(2): 91. CrossRef

Case Reports

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.

Citations

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Neurogenic tumours of the posterior mediastinum and differential diagnosis considerations
Michael A den Bakker, Annikka Weissferdt
Histopathology.2024; 84(1): 238. CrossRef
Hybrid tumors with perineurioma components: a systematic review of the literature and illustrative case
Karina A. Lenartowicz, Dileep D. Monie, Kimberly K. Amrami, Christopher J. Klein, Caterina Giannini, Robert J. Spinner
Acta Neurochirurgica.2022; 165(4): 935. CrossRef
Hybrid Schwannoma/Perineurioma: Morphologic Variations and Genetic Profiles
Takanori Hirose, Anna Kobayashi, Sumihito Nobusawa, Naoe Jimbo
Applied Immunohistochemistry & Molecular Morphology.2021; 29(6): 433. CrossRef
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Neurogenic Tumors of the Mediastinum
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Seminars in Diagnostic Pathology.2020; 37(4): 179. CrossRef
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
Diagnostic Pathology.2019;[Epub] CrossRef
Hybrid peripheral nerve sheath tumors: report of five cases and detailed review of literature
Nasir Ud Din, Zubair Ahmad, Jamshid Abdul-Ghafar, Rashida Ahmed
BMC Cancer.2017;[Epub] CrossRef
Primary intraosseous hybrid nerve sheath tumor of femur: A hitherto undescribed occurrence in bone with secondary aneurysmal bone cyst formation resulting in pathological fracture
Louis Tsun Cheung Chow
Pathology - Research and Practice.2015; 211(5): 409. CrossRef
Mesenchymal tumours of the mediastinum—part II
Michael A. den Bakker, Alexander Marx, Kiyoshi Mukai, Philipp Ströbel
Virchows Archiv.2015; 467(5): 501. CrossRef
Primary pleural hybrid cellular schwannoma/perineurioma: A case report
Danny Soria-Céspedes, Carlos Robles-Vidal, Arturo Gómez-González, Rosalinda Peñaloza-Ramírez, Carlos Ortiz-Hidalgo
Respiratory Investigation.2014; 52(4): 269. CrossRef
Hybrid peripheral nerve sheath tumour with intermingled perineuriomatous and schwannomatous areas reflected in skin ultrasonography image
H. Saeki, K. Ito, Y. Nobeyama, T. Ishiji, M. Fukunaga, H. Nakagawa
Clinical and Experimental Dermatology.2014; 39(6): 747. CrossRef
Périneuriome extraneural des tissus mous localisé au nez
A. Zaouak, R. Benmously, M. Belhadj Salah, W. Koubaa, A. Debbiche, I. Mokhtar
Annales de Dermatologie et de Vénéréologie.2013; 140(8-9): 540. CrossRef

A Case of Intimal Sarcoma Arising in the Left Common Iliac Artery.: Ji Young Park, Kun Young Kwon, Hyoung Tae Kim, Sang Sook Lee; Korean J Pathol. 2011;45(3):311-314.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.311

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Abstract PDF: Primary tumors of the great vessels are rare. Most encountered cases are sarcomas which most commonly develop in the aorta, pulmonary artery, and inferior vena cava. We experienced an intimal sarcoma arising in the left common iliac artery in a 68-year-old male, who suffered from claudication in his left lower extremity for a year and was diagnosed as arteriosclerosis obliterans, clinically. Bypass surgery was performed on the obstructive lesion. Grossly, the vascular lumen was filled with dark hemorrhagic materials. Microscopically, the lesion showed proliferation of anaplastic spindle cells with a marked nuclear atypia, arranged haphazardly. There were numerous mitotic figures. Foci of cholesterol clefts were also found in the intima. Immunohistochemically, the tumor cells were positive for vimentin, smooth muscle actin, and cytokeratin in certain areas. Stains for CD34, desmin, myosin heavy chain, caldesmon, and S-100 protein were negative. A pathologic diagnosis was made as intimal sarcoma with myofibroblastic differentiation.

Original Articles

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.

Citations

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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.

Citations

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Inhibition of MUC1-C Increases ROS and Cell Death in Mouse Embryonic Stem Cells
Jeong-A Park, Sangkyu Park, Jun-Kyu Choi, Myung-Kwan Han, Younghee Lee
International Journal of Stem Cells.2020;[Epub] CrossRef
Assessing the prognostic significance of MUC4β in mucoepidermoid carcinoma of the salivary glands: An immunohistochemical study
Poonam R. Sawant, Anita Spadigam, Anita Dhupar, Shaheen Syed, Karla Carvalho
Heliyon.2019; 5(11): e02753. CrossRef
Ultrasensitive cytosensing based on an aptamer modified nanobiosensor with a bioconjugate: Detection of human non-small-cell lung cancer cells
Tanveer A. Mir, Jang-Hee Yoon, N.G. Gurudatt, Mi-Sook Won, Yoon-Bo Shim
Biosensors and Bioelectronics.2015; 74: 594. CrossRef
Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma
Su-Mi Kim, Sun-Ju Oh, Bang Hur
Korean Journal of Pathology.2012; 46(5): 429. CrossRef
MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer
Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa, Fazlul H. Sarkar
PLoS ONE.2012; 7(11): e49251. CrossRef
Prognostic significance of membrane-associated mucins 1 and 4 in gastric adenocarcinoma
ILSEON HWANG, YU NA KANG, JIN YOUNG KIM, YOUNG ROK DO, HONG SUK SONG, KEON UK PARK
Experimental and Therapeutic Medicine.2012; 4(2): 311. CrossRef

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.

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.

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.

Flush Perfusion, Preservation and Reperfusion Effects in Lung Transplantation: Light Microscopic and Ultrastructural Study.: Kun Young Kwon, Young Keun Lim, Jae Hoon Bae, Chang Kwon Park; Korean J Pathol. 1998;32(11):967-977.

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Abstract: This study was undertaken to investigate the morphologic changes following flushing, preservation and reperfusion procedures in a canine lung allotransplantation model. Donor lungs were flushed with modified Euro-Collins (MEC) solution, low potassium dextran glucose (LPDG) solution or University of Wisconsin (UW) solution, then stored at 10oC for 20 hours. Light microscopic and electron microscopic features of the lungs were examined after flushing, preservation and 2 hours after reperfusion. After flushing light microscopy showed focal mild alveolar collapse and interstitial edema. After preservation the lung tissue showed multiple foci of alveolar collapse, consolidation, and alveolar epithelial cell damage. After reperfusion the lung tissue showed diffuse alveolar collapse, consolidation and many destroyed cellular debris in the alveolar lumina. After flushing electron microscopy showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. Some type I epithelial cells were detached from the basal lamina. The endothelial cells showed luminal protrusion of tactile-like structure and vacuoles of the cytoplasm. After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. After preservation scanning electron microscopic examination of the pulmonary arteries showed multiple patchy areas of swelling or conglomerated lesions in the inner surface of the pulmonary arteries. In conclusion, the ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage occurred during the reperfusion.

bcl-2 and p53 Protein Expression in Multiple Myeloma and Non-tumorous Plasma Cells A study related to survival.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Eun Sook Chang, Young Jae Lee; Korean J Pathol. 1999;33(3):179-186.

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Abstract PDF: The gene product of bcl-2 (B-cell leukemia/lymphoma-2) was suggested to suppress programmed cell death (apoptosis) of tumor cells and be involved in the development of multiple myeloma. However, the normal plasma cells also express the protein. It is unclear whether the expression of bcl-2 in multiple myeloma is of normal character or of regulatory adaptation in association with neoplastic transformation. p53 was also suggested to be involved in tumor progression since mutations on p53 were found in multiple myeloma. In order to find the relationship between the expression patterns of bcl-2 and p53 in tumor cells of multiple myeloma and non-neoplastic plasma cells, we examined 38 cases of multiple myeloma and 10 cases of nasal polyp immunohistochemically. Furthermore, expression of bcl-2 and p53, mitosis, clinical stage and infiltrative pattern of tumor cells in bone marrow were also evaluated in association with the survival of patients. By immunostaining with anti-bcl-2 and p53 monoclonal antibody, 37 out of 38 cases of multiple myeloma and all of 10 cases of nasal polyp were positive for bcl-2 but only 7 cases of multiple myeloma were positive for p53. Marked dysplasia, low percentage of bcl-2 expression, and increased mitoses were correlated with poor prognosis. Based on these observations, we suggest that bcl-2 and p53 are involved in tumorigenesis of multiple myeloma and the survival of patients would be influenced by dysplastic change, mitosis and degree of bcl-2 expression.

Case Report

Undescended Testis in the Complete Testicular Feminization Syndrome A report of three cases.: Yu Na Kang, Kwan Kyu Park, Kun Young Kwon, Sang Sook Lee, Jung Ho Lee, Jong In Kim; Korean J Pathol. 1999;33(5):371-375.

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Abstract PDF: The testicular feminization is the most common type of male pseudohermaphroditism. Mutation of androgen receptor gene impairs normal sexual differentiation in genetic male (46, XY) and subsequently develops secondary female characteristics. We report three cases of complete testicular feminization syndrome with normal development of female external genitalia, but with blindly ended vagina and inguinal or pelvic masses. Microscopic examination of the testes and their adnexa had three components: 1) A testis composed of immature tubules, prominent Leydig cells and a spindle cell stroma resembling ovarian stroma with hamartomatous nodule or Sertoli cell adenoma, 2) a white, whorled, firm, smooth muscle body in the medial pole of the testis, and 3) a lateral adnexal cysts of varying sizes.

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.

An Analysis of Histopathologic Evaluation of Lung Carcinomas in Last Ten Years.: Ji Min Jeon, Sun Young Kwon, Eun Sook Chang, Young Jun Jeon, Kun Young Kwon; Korean J Pathol. 1999;33(7):483-489.

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Abstract PDF: Lung cancer is one of the most common types of malignancy in western nations with serious health problem, and it has become the leading cause of cancer death of males, second only to stomach cancer, in Korea. A review of the histopathology of 1363 cases (1231 patients) of lung carcinoma, diagnosed at the Keimyung University Medical center from 1987 to 1996, was performed to reclassify the type of carcinomas and to investigate the change in the distribution of histologic types of lung carcinoma according to age, sex and year. Among the 1363 cases, 132 patients underwent a surgical operation after biopsy. The diagnosis of each case was proven by histopathologic analysis of surgical specimens (13.2%) and biopsy materials (86.8%). The histologic types in our study were basically based on modified WHO classification (1982) and on new WHO classification (1999). The classification of small cell carcinoma was based on International Association for the Small Cell Lung Cancer (IASLC, 1988). Of the 1231 patients with lung carcinoma, 1012 were male and 219 were female (male to female ratio was 3.6:1). According to the analysis of age distribution, the most prevalent age group was 60~69 years in both sex as (n=516, 42.0%). Changing trends in sex distribution of lung carcinoma patients showed that the proportion of men had decreased throughout the years, whereas the proportion of women had significantly increased. Histologically, squamous cell carcinoma was the most common (n=624, 50.7%), followed by small cell carcinoma (21.1%), adenocarcinoma (18.1%), large cell undifferentiated carcinoma (2.1%), adenosquamous carcinoma (0.4%), and large cell neuroendocrine carcinoma (0.4%), in order of frequency. In men, squamous cell carcinoma was the most frequent type (55.1%). In women, adenocarcinoma was the most frequent type (39.7%). In both sexes, adenocarcinoma was the most common type in patients under the age of 40 (n=12, 41.4%), while squamous cell carcinoma proved the most frequent type in patients over the age of 40 (n=617, 51.3%). Changing trends of histologic types of lung cancer showed that the incidences of squamous cell carcinoma had significantly decreased throughout the years, whereas those of adenocarcinoma and small cell carcinoma had increased. In conclusion, the results showing increases in the percentage of female patients and in the number of cases of adenocarcinoma were noteworthy, and well correlated with other related reports.

Morphologic Change of Proximal Convoluted Tubules in Radiation-Induced Renal Injury in Rats.: Eun Sook Chang, Kun Young Kwon, Ok Bae Kim; Korean J Pathol. 1999;33(8):555-569.

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Abstract PDF: Experimental studies suggest that captopril plays an important preventive role in radiation induced renal injury (RRI). To elucidate the pathogenesis of RRI and effect of captopril, one subgroup was irradiated with a single dose of 9 gray (Gy) total body irradiation and another subgroup with 17 Gy local irradiation in the right kidney. Twenty-four healthy looking Sprague-Dawley rats, weighing 200~250 g, were divided into one control and three experimental group (EG)s for this study. The control group, composed of 2 rats, was maintained on stock diet and drinking tap water. EG was divided into three. EG 1 composed of two subgroups, the first subgroup, 3 rats each, was sacrificed within 12 hours after 9 Gy and 17 Gy single dose irradiation only and the second subgroup, 2 and 1 rats each, was sacrificed 8 weeks after the same doses irradiation. EG 2 composed of subgroups of 2 and 3 rats was given 500 mg/L of captopril in the drinking water after irradiating them with 9 Gy and 17 Gy and sacrificed in the 8th week. EG 3 was subdivided into four subgroups by captopril doses given, 62.5 mg/L, 125 mg/L and 250 mg/L and sacrificed 20 weeks after 9 Gy and 17 Gy irradiation. On light microscopy proximal convoluted tubules showed cytoplasmic vacuolization and focal necrosis in the subcapsular region in EG 1 sacrificed within 12 hours after 9 Gy and 17 Gy irradiation only (sham) and very mild fibrosis in juxtamedullary regions in rats sacrificed 8 weeks after irradiation. In EG 3 these changes were severely increased with additional increased fibrosis in the juxtamedullary region in the group given captopril 62.5 mg/L. On transmission electron microscopy, there were various degenerative changes of organelle. Among the captopril administered EG 2 and EG 3, rats given a high dosage revealed milder degree of damage compared to that of rats given a low dosage, and thickening of basement membrane was remarkable in rats given a low dosage. There was a reduction in tubular damage related to the captopril dosage. According to the above findings, administration of a high dose of captopril might preserve the ultrastructure in RRI and the possible mechanism of captopril was discussed.

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