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Original Articles
Multistaining Optimization for Epstein-Barr Virus–Encoded RNA In Situ Hybridization and Immunohistochemistry of Formalin-Fixed Paraffin-Embedded Tissues Using an Automated Immunostainer
Jae Nam Ko, Jin Kyoung Jung, Yun Ik Park, Hwa Jeong Shin, Jooryung Huh, Sol Back, Yu Jin Kim, Jae Ho Kim, Heounjeong Go
J Pathol Transl Med. 2019;53(5):317-326.   Published online August 27, 2019
DOI: https://doi.org/10.4132/jptm.2019.08.06
  • 8,916 View
  • 128 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary Material
Background
Single staining is commonly performed for practical pathologic diagnoses. However, this method is limited in its ability to specify cellular morphology and immunophenotype and often requires consumption of limited tissue. This study aimed to describe an optimized protocol for multiple in situ hybridization (ISH) and immunohistochemistry (IHC).
Methods
The quality of multistaining was evaluated by carefully changing each step of ISH and IHC in an angioimmunoblastic T-cell lymphoma (AITL) case on a Ventana BenchMark XT automated immunostainer. The optimized protocols were also performed using another immunostainer and in 15 cases of five Epstein-Barr virus (EBV)–associated malignancies using formalin-fixed paraffin-embedded tissue.
Results
The quality of various ISHIHC staining protocols was semi-quantitatively evaluated. The best EBV-encoded RNA (EBER)-ISH/double IHC staining quality, equivalent to single staining, was obtained using the following considerations: initial EBER-ISH application, use of protease and antigen retrieval reagent (cell conditioning 1 [CC1] treatment time was minimized due to impact on tissue quality), additional baking/ deparaffinization not needed, and reduced dilution ratio and increased reaction time for primary antibody compared with single immunostaining. Furthermore, shorter second CC1 treatment time yielded better results. Multiple staining was the best quality in another immunostainer and for different types of EBV-associated malignancies when it was performed in the same manner as for the Ventana BenchMark XT as determined for AITL.
Conclusions
EBER-ISH and double IHC could be easily used in clinical practice with currently available automated immunostainers and adjustment of reagent treatment time, dilution ratio, and antibody reaction time.

Citations

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  • Clinicopathologic Analysis of 34 Japanese Patients With EBV-Associated Reactive Lymphoid Hyperplasias
    Yuuki Yamamoto, Akira Satou, Taishi Takahara, Daisuke Yamashita, Masafumi Seki, Akari Iwakoshi, Yusuke Ueda, Yasufumi Masaki, Kanae Yoshikawa, Hideki Murakami, Seiichi Kato, Kennosuke Karube, Shigeo Nakamura, Toyonori Tsuzuki
    American Journal of Surgical Pathology.2026;[Epub]     CrossRef
  • Ultra High-plex Spatial Proteogenomic Investigation of Giant Cell Glioblastoma Multiforme Immune Infiltrates Reveals Distinct Protein and RNA Expression Profiles
    Shilah A. Bonnett, Alyssa B. Rosenbloom, Giang T. Ong, Mark Conner, Aric B.E. Rininger, Daniel Newhouse, Felicia New, Chi Q. Phan, Saskia Ilcisin, Hiromi Sato, John S. Lyssand, Gary Geiss, Joseph M. Beechem
    Cancer Research Communications.2023; 3(5): 763.     CrossRef
  • Detection of Epstein–Barr Virus in Periodontitis: A Review of Methodological Approaches
    Lilit Tonoyan, Marlène Chevalier, Séverine Vincent-Bugnas, Robert Marsault, Alain Doglio
    Microorganisms.2020; 9(1): 72.     CrossRef
The Usefulness of Immunocytochemistry of CD56 in Determining Malignancy from Indeterminate Thyroid Fine-Needle Aspiration Cytology
Hyunseo Cha, Ju Yeon Pyo, Soon Won Hong
J Pathol Transl Med. 2018;52(6):404-410.   Published online October 15, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.20
  • 9,491 View
  • 175 Download
  • 6 Web of Science
  • 5 Crossref
AbstractAbstract PDF
Background
Fine-needle aspiration cytology serves as a safe, economical tool in evaluating thyroid nodules. However, about 30% of the samples are categorized as indeterminate. Hence, many immunocytochemistry markers have been studied, but there has not been a single outstanding marker. We studied the efficacy of CD56 with human bone marrow endothelial cell marker-1 (HBME-1) in diagnosis in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III.
Methods
We reviewed ThinPrep liquid-based cytology (LBC) samples with Papanicolaou stain from July 1 to December 31, 2016 (2,195 cases) and selected TBSRTC category III cases (n = 363). Twenty-six cases were histologically confirmed as benign (six cases, 23%) or malignant (20 cases, 77%); we stained 26 LBC slides with HBME-1 and CD56 through the cell transfer method. For evaluation of reactivity of immunocytochemistry, we chose atypical follicular cell clusters.
Results
CD56 was not reactive in 18 of 20 cases (90%) of malignant nodules and showed cytoplasmic positivity in five of six cases (83%) of benign nodules. CD56 showed high sensitivity (90.0%) and relatively low specificity (83.3%) in detecting malignancy (p = .004). HBME-1 was reactive in 17 of 20 cases (85%) of malignant nodules and was not reactive in five of six cases (83%) of benign nodules. HBME-1 showed slightly lower sensitivity (85.0%) than CD56. The specificity in detecting malignancy by HBME-1 was similar to that of CD56 (83.3%, p = .008). CD56 and HBME-1 tests combined showed lower sensitivity (75.0% vs 90%) and higher specificity (93.8% vs 83.3%) in detecting malignancy compared to using CD56 alone.
Conclusions
Using CD56 alone showed relatively low specificity despite high sensitivity for detecting malignancy. Combining CD56 with HBME-1 could increase the specificity. Thus, we suggest that CD56 could be a useful preoperative marker for differential diagnosis of TBSRTC category III samples.

Citations

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  • The Effects of Immunocytochemistry on Diagnostic Accuracy in Thyroid Fine Needle Aspiration Cytology: A Retrospective Study
    Ali Mızrak, Cansu Benli Işık, Esen Gül Uzuner, Saime Gül Barut
    Clinical and Experimental Health Sciences.2025; 15(3): 531.     CrossRef
  • Preoperative evaluation of thyroid nodules – Diagnosis and management strategies
    Tapoi Dana Antonia, Lambrescu Ioana Maria, Gheorghisan-Galateanu Ancuta-Augustina
    Pathology - Research and Practice.2023; 246: 154516.     CrossRef
  • Immunocytochemistry in thyroid cytology and its multiple roles: a systematic review
    Federica Policardo, Pietro Tralongo, Angela Feraco, Federica Vegni, Angela Carlino, Alfredo Pontecorvi, Celestino Pio Lombardi, Marco Raffaelli, Francesco Pierconti, Luigi Maria Larocca, Esther Diana Rossi
    Diagnostic Histopathology.2023; 29(8): 386.     CrossRef
  • Paving the path toward multi-omics approaches in the diagnostic challenges faced in thyroid pathology
    Isabella Piga, Vincenzo L’Imperio, Giulia Capitoli, Vanna Denti, Andrew Smith, Fulvio Magni, Fabio Pagni
    Expert Review of Proteomics.2023; 20(12): 419.     CrossRef
  • CD56 Expression in Papillary Thyroid Carcinoma Is Highly Dependent on the Histologic Subtype: A Potential Diagnostic Pitfall
    Uiju Cho, Yourha Kim, Sora Jeon, Chan Kwon Jung
    Applied Immunohistochemistry & Molecular Morphology.2022; 30(5): 389.     CrossRef
Loss of Nuclear BAP1 Expression Is Associated with High WHO/ISUP Grade in Clear Cell Renal Cell Carcinoma
Young Chan Wi, Ahrim Moon, Min Jung Jung, Yeseul Kim, Seong Sik Bang, Kiseok Jang, Seung Sam Paik, Su-Jin Shin
J Pathol Transl Med. 2018;52(6):378-385.   Published online October 1, 2018
DOI: https://doi.org/10.4132/jptm.2018.09.21
  • 10,797 View
  • 228 Download
  • 14 Web of Science
  • 14 Crossref
AbstractAbstract PDF
Background
BRCA1-associated protein 1 (BAP1) mutations are frequently reported in clear cell renal cell carcinoma (ccRCC); however, very few studies have evaluated the role of these mutations in other renal cell carcinoma (RCC) subtypes. Therefore, we analyzed BAP1 protein expression using immunohistochemistry in several RCC subtypes and assessed its relationship with clinicopathological characteristics of patients.
Methods
BAP1 expression was immunohistochemically evaluated in tissue microarray blocks constructed from 371 samples of RCC collected from two medical institutions. BAP1 expression was evaluated based on the extent of nuclear staining in tumor cells, and no expression or expression in < 10% of tumor cells was defined as negative.
Results
Loss of BAP1 expression was observed in ccRCC (56/300, 18.7%), chromophobe RCC (6/26, 23.1%), and clear cell papillary RCC (1/4, 25%), while we failed to detect BAP1 expression loss in papillary RCC, acquired cystic disease-associated RCC, or collecting duct carcinoma. In ccRCC, loss of BAP1 expression was significantly associated with high World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grade (p = .002); however, no significant correlation was observed between loss of BAP1 expression and survival in ccRCC. Loss of BAP1 expression showed no association with prognostic factors in chromophobe RCC.
Conclusions
Loss of BAP1 nuclear expression was observed in both ccRCC and chromophobe RCC. In addition, BAP1 expression loss was associated with poor prognostic factors such as high WHO/ISUP grade in ccRCC.

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    Ziwei Gui, Juan Du, Nan Wu, Ningning Shen, Zhiqing Yang, Huijun Yang, Xuzhi Wang, Na Zhao, Zixin Zeng, Rong Wei, Wenxia Ma, Chen Wang
    BMC Cancer.2023;[Epub]     CrossRef
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    Derek H Liu, Komal A Dani, Sharath S Reddy, Xiaomeng Lei, Natalie L Demirjian, Darryl H Hwang, Bino A Varghese, Suhn Kyong Rhie, Felix Y. Yap, David I. Quinn, Imran Siddiqi, Manju Aron, Ulka Vaishampayan, Haris Zahoor, Steven Y Cen, Inderbir S Gill, Vinay
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    Mahmut Akgul, Sean R Williamson
    Seminars in Diagnostic Pathology.2022; 39(1): 1.     CrossRef
  • BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review
    Shuchi Gulati, Melissa Previtera, Primo N. Lara
    Kidney Cancer.2022; 6(1): 23.     CrossRef
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    Ziad M. El-Zaatari, Luan D. Truong
    Biomedicines.2022; 10(3): 657.     CrossRef
  • CD117, BAP1, MTAP, and TdT Is a Useful Immunohistochemical Panel to Distinguish Thymoma from Thymic Carcinoma
    Mounika Angirekula, Sindy Y Chang, Sarah M. Jenkins, Patricia T. Greipp, William R. Sukov, Randolph S. Marks, Kenneth R. Olivier, Stephen D. Cassivi, Anja C Roden
    Cancers.2022; 14(9): 2299.     CrossRef
  • BAP1 in cancer: epigenetic stability and genome integrity
    Sabrina Caporali, Alessio Butera, Ivano Amelio
    Discover Oncology.2022;[Epub]     CrossRef
  • Bioinformatic analysis identifying FGF1 gene as a new prognostic indicator in clear cell Renal Cell Carcinoma
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  • Identification of Four Pathological Stage‐Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis
    Dengyong Xu, Yuzi Xu, Yiming Lv, Fei Wu, Yunlong Liu, Ming Zhu, Dake Chen, Bingjun Bai, Rui Liu
    BioMed Research International.2020;[Epub]     CrossRef
  • Functional characterisation guides classification of novel BAP1 germline variants
    Jing Han Hong, Siao Ting Chong, Po-Hsien Lee, Jing Tan, Hong Lee Heng, Nur Diana Binte Ishak, Sock Hoai Chan, Bin Tean Teh, Joanne Ngeow
    npj Genomic Medicine.2020;[Epub]     CrossRef
  • Tissue-Based Immunohistochemical Markers for Diagnosis and Classification of Renal Cell Carcinoma
    Liang G Qu, Vaisnavi Thirugnanasundralingam, Damien Bolton, Antonio Finelli, Nathan Lawrentschuk
    Société Internationale d’Urologie Journal.2020; 1(1): 68.     CrossRef
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    Zuhir Bodalal, Stefano Trebeschi, Thi Dan Linh Nguyen-Kim, Winnie Schats, Regina Beets-Tan
    Abdominal Radiology.2019; 44(6): 1960.     CrossRef
Review
Article image
Immunohistochemistry for Pathologists: Protocols, Pitfalls, and Tips
So-Woon Kim, Jin Roh, Chan-Sik Park
J Pathol Transl Med. 2016;50(6):411-418.   Published online October 13, 2016
DOI: https://doi.org/10.4132/jptm.2016.08.08
  • 65,535 View
  • 2,435 Download
  • 330 Web of Science
  • 321 Crossref
AbstractAbstract PDF
Immunohistochemistry (IHC) is an important auxiliary method for pathologists in routine diagnostic work as well as in basic and clinical research including exploration of biomarkers, as IHC allows confirmation of target molecule expressions in the context of microenvironment. Although there has been a considerable progress in automation and standardization of IHC, there are still many things to be considered in proper optimization and appropriate interpretation. In this review, we aim to provide possible pitfalls and useful tips for practicing pathologists and residents in pathology training. First, general procedure of IHC is summarized, followed by pitfalls and tips in each step and a summary of troubleshooting. Second, ways to an accurate interpretation of IHC are discussed, with introduction to general quantification and analysis methods. This review is not intended to provide complete information on IHC, but to be used as a basic reference for practice and publication.

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Original Articles
Expression of CD99 in Multiple Myeloma: A Clinicopathologic and Immunohistochemical Study of 170 Cases
Su-Jin Shin, Hyangsin Lee, Geunyoung Jung, Minchan Gil, Hosub Park, Young Soo Park, Dok Hyun Yoon, Cheolwon Suh, Chan-Jeoung Park, Jooryung Huh, Chan-Sik Park
Korean J Pathol. 2014;48(3):209-216.   Published online June 26, 2014
DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.3.209
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AbstractAbstract PDF
Background

Multiple myeloma (MM) is a heterogeneous and ultimately fatal disease. Risk stratification using prognostic biomarkers is crucial to individualize treatments. We sought to investigate the role of CD99, a transmembrane protein highly expressed in many hematopoietic cells including subpopulations of normal and neoplastic plasma cells, for MM risk stratification.

Methods

CD99 expression was measured in paraffin samples of bone marrow and extramedullary biopsies of 170 patients with MM. Patients were divided into those with high score (moderately and strongly positive) and low score (negative and weakly positive), with all staining being cytoplasmic and/or membranous.

Results

High anti-CD99 immunostaining was observed in 72 of 136 (52.9%) bone marrow biopsies and 24 of 87 (27.6%) extramedullary biopsies in MM. High CD99 expression of extramedullary specimens was associated with significantly longer overall survival (OS; p=.016). High CD99 expression of extramedullary specimens was also associated with better prognosis in the nonautologous stem cell transplantation group of MM patients (p=.044). In multivariate analysis, International Staging System stage was an independent prognostic factor, whereas CD99 expression was no longer statistically significant.

Conclusions

Expression of CD99 in extramedullary specimens was correlated with longer OS, suggesting that CD99 may be a helpful immunohistochemical marker for risk stratification.

Citations

Citations to this article as recorded by  
  • Cell Adhesion Molecule CD99 in Cancer Immunotherapy
    Feng Yu, Guodong Liu, Hailing Zhang, Xiaoyan Wang, Zhi Wu, Qinggang Xu, Yan Wu, Dongfeng Chen
    Current Molecular Medicine.2023; 23(10): 1028.     CrossRef
  • Detection of Circulating Tumor Plasma Cells in Monoclonal Gammopathies: Methods, Pathogenic Role, and Clinical Implications
    Luzalba Sanoja-Flores, Juan Flores-Montero, Martín Pérez-Andrés, Noemí Puig, Alberto Orfao
    Cancers.2020; 12(6): 1499.     CrossRef
  • Tumor suppressor CD99 is downregulated in plasma cell neoplasms lacking CCND1 translocation and distinguishes neoplastic from normal plasma cells and B-cell lymphomas with plasmacytic differentiation from primary plasma cell neoplasms
    Qi Gao, Venkata Yellapantula, Maly Fenelus, Janine Pichardo, Lu Wang, Ola Landgren, Ahmet Dogan, Mikhail Roshal
    Modern Pathology.2018; 31(6): 881.     CrossRef
  • EWSR1 fusion proteins mediate PAX7 expression in Ewing sarcoma
    Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
    Modern Pathology.2017; 30(9): 1312.     CrossRef
  • Activation of the polycomb repressive complex pathway in the bone marrow resident cells of diffuse large B-cell lymphoma patients
    Eun Ji Oh, Eun Kyung Kim, Woo Ick Yang, Sun Och Yoon
    Leukemia & Lymphoma.2016; 57(8): 1921.     CrossRef
  • CD99 Is Strongly Expressed in Basal Cells of the Normal Adult Epidermis and Some Subpopulations of Appendages: Comparison with Developing Fetal Skin
    Gawon Choi, Jin Roh, Chan-Sik Park
    Journal of Pathology and Translational Medicine.2016; 50(5): 361.     CrossRef
  • Towards Stratified Medicine in Plasma Cell Myeloma
    Philip Egan, Stephen Drain, Caroline Conway, Anthony Bjourson, H. Alexander
    International Journal of Molecular Sciences.2016; 17(10): 1760.     CrossRef
  • Human Myeloma Cell Lines Induce Osteoblast Downregulation of CD99 Which Is Involved in Osteoblast Formation and Activity
    Angela Oranger, Giacomina Brunetti, Claudia Carbone, Graziana Colaianni, Teresa Mongelli, Isabella Gigante, Roberto Tamma, Giorgio Mori, Adriana Di Benedetto, Marika Sciandra, Selena Ventura, Katia Scotlandi, Silvia Colucci, Maria Grano
    Journal of Immunology Research.2015; 2015: 1.     CrossRef
  • CD99 regulates CXCL12-induced chemotaxis of human plasma cells
    Minchan Gil, Hyo-Kyung Pak, A-Neum Lee, Seo-Jung Park, Yoonkyung Lee, Jin Roh, Hyunji Lee, Yoo-Sam Chung, Chan-Sik Park
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Evaluation of Bronchiolar and Alveolar Cell Injuries Induced by Short- and Long-term Exposure to Sidestream Smoke
Kun-Young Kwon, Hye-Ra Jung, Ilseon Hwang, Won-Il Choi
Korean J Pathol. 2012;46(2):151-161.   Published online April 25, 2012
DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.2.151
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AbstractAbstract PDF
Background

We investigated effects of short- and long-term exposure to sidestream smoke on the bronchiolar and alveolar cells in Sprague-Dawley rats.

Methods

Rats were divided into five experimental groups: groups 1, 2, and 3 (1-month exposure to 3, 5, and 7 cigarettes a day, respectively), groups 4 and 5 (3- and 6 month exposure to five cigarettes a day, respectively). We examined the morphologic changes, the expressions of tumor necrosis factor α (TNF-α), tumor growth factor β1 (TGF-β1), interlekin (IL)-1α, IL-1β, Ki-67, and cytokeratin 14 and in situ apoptosis in the bronchiolar and alveolar cells on light microscopy (LM) and electron microscopic (EM) terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.

Results

LM showed the respiratory bronchiolar dilatation and alveolar wall collapse. In groups 3, 4, and 5, EM showed loss of the cilia and Clara cells with irregular size, more prominent alveolar wall collapse and dilation of alveolar duct than those of groups 1 and 2. Bronchiolar and alveolar cells showed increased expressions of TNF-α and TGF-β in groups 4 and 5. LM and EM TUNEL stains showed increased apoptosis in groups 3, 4, and 5.

Conclusions

Sidestream smoke causes a bronchiolar and alveolar cell injury and the severity correlates strongly the volume and duration of exposure to sidestream smoke.

Citations

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  • Cigarette smoke extract alters the cell cycle via the phospholipid transfer protein/transforming growth factor-β1/CyclinD1/CDK4 pathway
    Xue-Min Chai, You-Lun Li, Hong Chen, Shu-Liang Guo, Li-Li Shui, Ya-Juan Chen
    European Journal of Pharmacology.2016; 786: 85.     CrossRef
  • Keratin-14 Expression in Pneumocytes as a Marker of Lung Regeneration/Repair during Diffuse Alveolar Damage
    Miriam Ficial, Caterina Antonaglia, Marco Chilosi, Mario Santagiuliana, Al-Omoush Tahseen, Davide Confalonieri, Lorenzo Zandonà, Rossana Bussani, Marco Confalonieri
    American Journal of Respiratory and Critical Care Medicine.2014; 189(9): 1142.     CrossRef
Case Report
Cytologic Findings of Alveolar Soft Part Sarcoma Presenting with Multiple Pulmonary Masses: A Case Report with Review of Literature.
Na Rae Kim, Jae Y Ro, Eun Kyung Cho, Mi Jin Kim, Jungsuk An, Seung Yeon Ha
Korean J Pathol. 2011;45(1):119-124.
DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.1.119
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AbstractAbstract PDF
Alveolar soft part sarcoma (ASPS) is a rare malignant soft tissue tumor of uncertain origin, and it has a strong propensity for metastasis to the lungs, bones and brain. We report upon an unusual case of ASPS, presenting as multiple lung nodules with no other detectable primary site, in a 44-year-old man. A fine needle aspiration of the nodules yielded scattered, discohesive cells, each containing an eccentrically displaced nucleus and prominent nucleolus, on a granular background. Tumor cells with numerous bared nuclei, and occasional sheets of epithelioid cells were also found. Under the cytological diagnosis of an unclassified epithelioid malignant tumor, resection of the lung nodules was performed. The histologic findings were consistent with ASPS, showing positive TFE3-nuclear immunoreactivity. There is limited literature concerning cytological findings associated with pulmonary ASPS: especially in cases where the primary site is unknown. Here, we present a cytological review of pulmonary ASPS, investigating the significance of TFE3 staining in the diagnosis of ASPS.

Citations

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  • Alveolar soft part sarcoma: A case report with emphasis on some unusual cytological features
    Neelam Sood, Minakshi Gulia
    Diagnostic Cytopathology.2018; 46(2): 170.     CrossRef
Original Articles
Comparison of Various Detection Methods of Mycobacterium Species in Formalin-Fixed Paraffin-Embedded Tissue with Chronic Granulomatous Inflammation.
Hyun Seung Lee, Hyoungnam Lee, Soyoung Im, Yun Su Lee, Kyo Young Lee, Yeong Jin Choi
Korean J Pathol. 2010;44(3):259-266.
DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.3.259
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AbstractAbstract PDF
BACKGROUND
To determine the most effective method for detecting mycobacteria in formalin- fixed paraffin-embedded (FFPE) tissue, we compared the results of Ziehl-Neelsen stain (ZNS) and mycobacterial culture with those of polymerase chain reaction (PCR) and real-time quantitative PCR (RQ-PCR).
METHODS
We analyzed 54 cases diagnosed as chronic granulomatous inflammation. In all cases, ZNS and nested PCR using three different primers, IS6110, Mpb64 and IS6110/Rpobeta were done. RQ-PCR with the IS6110/Rpobeta primer was done in 51 cases.
RESULTS
Mycobacteria were identified by ZNS in 15/54 (27.8%) cases. RQ-PCR had the highest sensitivity (80.0%) compared to PCR with IS6110 (73.3%), Mpb64 (60.0%) and IS6110/Rpobeta (73.3%). Specificity was higher in all PCR experiments (79.5-82.1%) than in RQ-PCR (69.4%) experiments. The false negative rate was lowest for RQ-PCR (20.0%) than for PCR with IS6110 (26.7%), Mpb64 (40.0%) and IS6110/Rpobeta (26.7%). The false positive rate was highest for RQ-PCR (30.6%) compared to PCR with IS6110 (20.5%), Mpb64 (17.9%) and IS6110/Rpobeta (20.5%).
CONCLUSIONS
RQ-PCR had the highest sensitivity, and the lowest false negative rate, but it also had a higher false positive rate than PCR for detection of mycobacteria in FFPE tissues.

Citations

Citations to this article as recorded by  
  • Clinical Usefulness of PCR for Differential Diagnosis of Tuberculosis and Nontuberculous Mycobacterial Infection in Paraffin-Embedded Lung Tissues
    Yo Na Kim, Kyoung Min Kim, Ha Na Choi, Ju Hyung Lee, Ho Sung Park, Kyu Yun Jang, Woo Sung Moon, Myoung Jae Kang, Dong Geun Lee, Myoung Ja Chung
    The Journal of Molecular Diagnostics.2015; 17(5): 597.     CrossRef
  • Usefulness of PCR to Mycobacterium Tuberculous and Nontuberculous Mycobacteria from Paraffin-embedded Tissues
    Yeon-Il Choi, Hye-Young Kim
    Korean Journal of Clinical Laboratory Science.2014; 46(2): 47.     CrossRef
The Cytology for Leukemic Cells in Cerebrospinal Fluid; Comparison of Conventional Cytology with Liquid-Based Cytology.
Changyoung Yoo, Youn Soo Lee, Chang Suk Kang, Sang In Shim, Kyo Young Lee
Korean J Pathol. 2009;43(2):164-170.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.164
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AbstractAbstract PDF
BACKGROUND
The cytological examination of cerebrospinal fluid (CSF) using conventional cytology with a cytocentrifuge (cytospin) is an important method for evaluating the involvement of leukemia in the CNS. Liquid-based cytology (LBC) is now a widely used cytological method not only for gynecological and non-gynecological specimens, but its application to CSF for the identification of leukemic cell has not yet been reported. In this study, we tried to compare conventional cytology with using a cytospin with LBC and Papanicolaou (Pap) staining. We also examined the modified LBC with Wright staining to assess whether this modified method can be useful for diagnosing Leukemia.
METHODS
We studied 30 cases of CSF that were obtained from 16 patients, including 17 cases of acute myeloid leukemia, 12 cases of acute lymphoblastic leukemia and 1 case of diffuse large B cell lymphoma. We applied conventional cytology with a cytocentrifuge (cytospin), LBC with Pap staining and modified LBC with Wright staining.
RESULTS
The morphological features of the LBC with Pap staining showed difficulty for interpretation when compared with conventional cytology with a cytospin, and mainly because of cellular shrinkage. The modified LBC with Wright staining showed good morphological features.
CONCLUSIONS
We suggest that modified LBC with Wright staining may be useful for examining CSF.
Nucleolar Organizer Regions in Normal Tissue and Hyperplastic and Neoplastic Lesions.
Joon Mee Kim, In Sun Kim, Seung Yong Paik
Korean J Pathol. 1989;23(2):208-222.
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AbstractAbstract PDF
For the identification of proliferating cells in tissue, the argyrophilic method for the demonstration of nucleolar organizer regions (Ag-NORs) have been described. To evaluate the applicability of Ag-NORs in surgical pathology, the authors have done Ag-NORs staining on 144 cases of routinely processed, formalin-fixed paraffin sections of various tissues; 15 normal tissues, 12 reactive and hyperplastic lesions, 30 benign neoplasms, 4 borderline lesions, and 83 malignant tumors. The results were summerized as follows; 1) In normal tissues, the mean numbers of Ag-NORs were highter in labile cells, especially in actively proliferating cells such as germ cells of testis, crypt epithelial cells in gastrointestinal mucosa, and lymphocytes from germinal center of tonsil and lymph node, than those of stable cells. 2) The mean numbers of Ag-NORs in reactive and hyperplastic lesions, benign neoplasms, and borderline lesions were similar to those of normal labile cells. 3) The mean numbers of Ag-NORs in carcinomas and sarcomas, (usually more than 2) significantly exceeded those of normal and non-malignant conditions. However, certain cases of carcinomas such as papillary carcinomas of thyroid, mucinous carcinoma of stomach, bronchioloalveolar carcinoma of lung, and adenoid cystic carcinoma of lung, and some of the leiomyosarcoma, malignant fibrous histiocytoma, and malignant schwannoma showed relatively lower numbers of Ag-NORs. 4) In non-Hodgkin's lymphomas, the high grade lymphomas showed more Ag-NORs than the low grade ones. From above results, it is suggested that the Ag-NORs technique is helpful in differentiation between malignant and non-malignant lesions. However, further evaluation on the significance of Ag-NORs upon the behavior of the cancer is to be made.
Availability of Toluidine Blue Stain in Body Fluid.
Hye Kyung Lee, Myung Jin Joo, Kwang Min Lee, Eun Hee Lee, Sang In Sim
J Pathol Transl Med. 1999;10(1):7-11.
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AbstractAbstract PDF
We evaluated the availability of toluidine blue stain in body fluids, such as peritoneal and pleural fluid and urine. Nine hundreds specimens, i.e., 400 pleural and 400 peritoneal fluids and 100 urine samples, respectively, from Jan. 1995 to May 1996 were included. We obtained the result of high sensitivity and high specificity in toluidine blue stained body fluid in comparison with Papanicolaou stained result. Additionally, we found the diagnostically important crystals in chylothorax and some urine samples, which can not be seen in routine Papanicolaou stain. We thought the toluidine blue stain in body fluid is one of very useful diagnostic methods.
Histopathologic Re-evaluation of Thymoma with Immunonhistochemical Study for bcl-2 and MIC-2 Protein.
Kyung Moo Yang, Mee Yon Cho, Soon Won Hong, Tae Seung Kim, Chan Il Park, Woo Ick Yang
Korean J Pathol. 1997;31(5):446-461.
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AbstractAbstract PDF
We reviewed 86 thymic epithelial tumors and reclassified them according to the Kirchner and Muller- Hermelink classification. They were subtyped as medullary, mixed, predominantly cortical (organoid), cortical, well differentiated thymic carcinoma, and poorly differentiated thymic carcinoma. The frequency of each subtype was determined and histologic findings were related to stage and myasthenia gravis. Immunohistochemical stains for bcl-2 protein as a marker for medullary thymocytes and MIC-2 protein as a marker for cortical thymocytes were performed in each case. The stages and association of myasthenia gravis was significantly different in each subtypes. The results of this study demonstrate that this histogenetic classification is clinically applicable. The bcl-2 protein was specifically demonstrated in lymphocytes within areas of medullary differentiation and MIC-2 protein in cortical differentiation. The expression of bcl-2 and MIC-2 proteins lend histogenetic support for this new classification of thymoma. Bcl-2 protein is strongly expressed in tumor epithelial cells of every case of poorly differentiated thymic carcinoma whereas the other types of thymic epithelial tumors do not show epithelial expression of this protein. The strong expression of bcl-2 protein in tumor epithelium may be considered as a predictor of aggressive behavior in thymic epithelial tumors.
Nature of Stromal Cells in Cerebellar Capillary Hemangioblastoma: Immunohistochemical analysis.
Soon Won Hong, Tai Seung Kim, Ji Young Han
Korean J Pathol. 1995;29(5):584-589.
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AbstractAbstract
The origin of the stromal cell of cerebellar hemangioblastoma has long been studied electron microscopically and immunohistochemically. The results and theories about the stromal cell origin are variable and plentiful. However, the exact origin of the stromal cell remains controversial. The present study is aimed to elucidate the nature of the stromal cell of cerebellar hemangioblastoma. Ten cases of hemangioblastoma in Severance Hospital were used for immunohistochemical analysis of the stromal cell. The immunohistochemical staining of GFAP, S-100 protein, NSE, alpha-l-antichymottypsin, cytokeratin, CD 68, factor VIII related antigen, and synaptophysin were performed. The results were as follows; GFAP and S-100 protein were stained mainly but weakly in bellar capillary spindle cell and cellular process. NSE was stained mainly in foam cells, and 6 cases among them revealed strong reaction. ct-l-antichymotrypsin was stained in a few foam cells of 5 cases. Cytokeratin, CD 68, factor VIII related antigen, and synaptophysin showed negative reaction. Based on these results, it is considered that the origin of the stromal cell is histiocytic or neurogenic rather than glial. The weak positivity of GFAP and S-100 protein may support the neurogeriic origin but ct-l-antichymotrypsin positivity does not support the possibility. The positivity of GAP and S-100 protein supports the phagocytic action of histiocytic cell and suggests histiocytic origin rather than neurogenic.
Expression of p53 Protein and c-erbB-2 Oncoprotein in Breast Carcinoma.
Eun Hee Lee, Dong Sug Kim, Tae Sook Lee, Soo Jung Lee
Korean J Pathol. 1995;29(5):596-606.
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AbstractAbstract
This study was conducted to evaluate the expression of p53 and c-erbB-2 using immuno-histochemical methods in 145 primary breast carcinomas and to correlate it with other histo-pathological prognostic factors. Invasive ductal carcinoma represented 129 of the cases. Expression of p53 protein and c-erbB-2 oncoprotein was present in 48% (62/129) and 30% (39/129) of invasive ductal carcinomas, respectively. The expression of p53 protein was stongly associated with a high score of degree of differentiation (p<0.05), nuclear pleomorphism (p<0.05), mitotic index (p<0.05), SBR grade (p<0.05) and MSBR grade (p<0.05), but it was not associated with patient's age, size of tumor or axillary node metastasis. The overexpression of c-erbB-2 C-erbB-2 oncoprotein was strongly associated with a high score of nuclear pleomorphism and a high SBR grade (p<0.05), but not associated with patient's age, size of tumor, axillary node metastasis, degree of differentiation, mitotic index or MSBR grade. An inverse relationship between the expression of p53 protein and estrogen receptor status was found, but the expression of c-erbB-2 was not associated with estrogen receptor status. It is concluded that p53 protein and c-erbB-2 oncoprotein are important prognostic factors in breast cancers, and that the aberrant expression of p53 protein is the most useful prognostic factor becausd of strong association of known histopathological prognostic factors and negative estrogen receptor status.
Comparative Assessment of Immunohistochemical and Zieh1-Neelsen Stains for Demonstration of Mycobacterium Tuberculosis.
Mee Yon Cho, Soon Hee Jung, Woo Ick Yang
Korean J Pathol. 1993;27(3):243-248.
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AbstractAbstract PDF
To obtain a useful method for the identification of mycobacteria in tissue section, we evaluated 118 cases of tuberculosis: 48 pulm onary, 14 lymph nodal and 56 synovial tuberculosis. Seventy nine of these cases underwent the culture study. Sections stained with anti-Mycobacterium bovis were compared with the results of the Zieh1-Neelsen stain and culture. The immunohistochemical stain for Mycobacterium bovis in al examined cases was not any more sensitive than the Zieh1-Neelsen stain(p>0.05). Neverthless, the immunohistochemical stain was a useful method for the localization of mycobacteria because of the striking contrast between its background and the wider dimension of a positive area. Immunoreactive areas demonstrated a few intact mycobacteria showing a positive reaction in the Zieh1-Neelsen stain. In conclusion, double staining method using the immunohischemical stain for Mycobacterium bovis and the Zieh1-Neelsen stain is an efficient technique in oder to confirm the diagnosis of tuberculosis.
Case Report
Toxoplasmic Lymphadenitis with Toxoplasma Bradyzoites: A Case Report.
Hwa Eun Oh, Insun Kim
Korean J Pathol. 2004;38(5):330-332.
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AbstractAbstract PDF
Toxoplasmic lymphadenitis is the most frequently observed clinical form of acquired toxoplasmosis. It is diagnosed by observing the characteristic histopathology, performing serologic tests and demonstrating the organisms. However, detection of the organisms in lymph node section is rarely accomplished. We demonstrate a case of a toxoplasmic lymphadenitis of a 40-year-old man with bradyzoites. The histopathologic findings of the lymph nodes showed reactive follicular hyperplasia associated with the presence of irregular clusters of epithelioid histiocytes, usually located in the cortical and paracortical zones, and monocytoid B cell proliferation. We demonstrated the bradyzoites of Toxoplasma gondii with periodic acid-Schiff (PAS)-stain, and serologic testing showed positive Ig-G and Ig-M toxoplasma antibodies.
Original Articles
The Effect of Common Bile Duct Ligation on Liver Morphology and Coper Metabolism in Rat.
Kyoung Sook Kim, Chanil Park, Jang Whan Cho, In Joon Choi, Yoo Bock Lee
Korean J Pathol. 1990;24(4):402-411.
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AbstractAbstract PDF
To clarity the effect of biliary obliteration on copper metabolism of rat liver and on the hepatic morphology, 0.5% cuppuric sulfate was administered intraperitoneally for 42 days following ligation of the common bile duct (CBD) of Sprague-Dawley rats. The blood copper concentration, the hepatic copper content and the accumulation patterns of copper and copper binding protein in the liver were examined and compared with those of the simple CBD ligation group and the simple copper over loaded group. CBD ligation induced marked proliferation of bile ductular structures which, after expanding the portal tracts, invaded and divided the hepatic lobules. There was, however, no excess fibosis beyond what needed to support the new ductules. The blood copper concentration and the hepatic copper content were increased by copper overload with or without CBD ligation, particularly incases with CBD ligation. Liver cell necrosis did not occur by the overloaded copper alone in rats. The hepatic copper and copper binding protein were accumulated at periportal liver cells in the group of coppe overload after CBD ligatio, whereas they began to appear at perivenular hepatocytes in the simple copper overloaded group. In conclusion, it is suggested that CBD ligation does not induce excess fibrosis or liver cirrhosis in rat as far as during our experimental period, but affect significantly on copper metabolism by intrahepatic redistribution of the copper and the copper binding proteins.
Histopathologic and Immunohistochemical observation on Malignant Schwannoma.
Tae Sook Hwang, Seong Hoe Park, Eui Keun Ham
Korean J Pathol. 1990;24(4):446-455.
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AbstractAbstract PDF
Histopathologic and immunohistochemical analysis using antibodies for S-100 protein and keratin has been conducted on 21 cases of malignant schwannomas. The 21 cases were divided into the following three groups Group A: tumors originating from the nerve trunk or neurofibroma; Group B: tumors related to von Recklinghausen's disease; and Group C: other tumors not belonging to the above groups but histologically diagnosed as malignant schwannoma. The commonest histological pattern consisted of either closely packed or loosely arranged interlacing fascicles of slender spindle cells with wavy fibrillar cytoplasm, followed by myxoid change, perithelial pattern, hyaline change of the blood vessels, and hyalinlzed cords or nodules. Nine out of 12 cases of malignant schwannomas in group A and B, and 7 out of 9 cases of group C were positive for S-100 protein. None of the above cases showed positive staining reaction for keratin. Since 7 of 9 malignant schwannomas in Group C stained with S-100 protein, we can conclude that careful histological analysis supplemented by immunohistichemical study can make a conclusive diagnosis in most of the cases of malignant schwannomas even in cases that do not fulfil the traditional strict criteria.
Immunohistochemical Study of the Expression of the p53 Protein in Primary Lung Cancer.
Sang Yong Lee, Jin Sook Jeong, Sook Hee Hong
Korean J Pathol. 1996;30(3):218-227.
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AbstractAbstract PDF
An immunohistochemical stain for p53 tumor suppressor gene product was performed in 59 primary lung cancers to study the relation between its expression and type of the tumor, degree of tumor differentiation,clinical stage and smoking. The results were as follows: 1. The expression of mutant p53 protein was noted in 28 of 59 cases(47.5%) of primary lung cancers. The p53 protein was expressed in 21 of 35(60%) squamous cell carcinomas, in 6 of 21(28.6%) adenocarcinomas, and 1 of 1(100%) small cell carcinoma. There was a significant difference in expression of p53 among the different histologic types of lung cancer(p<0.05). 2. The incidence of p53 protein expression did not correlate with the degree of tumor cell differentiation or the clinical stage of lung carcinoma(p>0.05). 3. The incidence of p53 protein expression was higher in smokers(current: 75%, former: 46.2%) than in non-smokers(5.6%) and was increased in direct proportion to the pack years. There was a statistically significant correlation between p53 expression and smoking(p<0.05). The mutation of p53 gene may often be an early event in the development of lung cancer and it is suggested that the smoking known as a risk factor for the development of the lung cancer may be associated with the transformation of p53 tumor suppressor gene into mutant p53 gene or oncogene.
Case Report
Primary Cerebral B Cell Lymphoma: A "ghost tumor" case report.
Hye Jae Cho, Jung Won Shim, Sang Keun Park, Joon Suk Song, Gham Hur, Hyun Sook Seo
Korean J Pathol. 1991;25(1):68-75.
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AbstractAbstract PDF
Primary non-Hodgkin's lymphoma of the brain is a rare malignancy and there are known to occur almost exclusively in brain parenchyme. Recent immunological advances and immunohistochemical techniques have provided new insights into the pathogenesis and diagnosis of the malignant lymphoma even in the small biopsied tissue and the majority of these CNS tumors is thought to be derived from B lymphocytes. A 22-year old man was admitted due to headack, dizziness and walking difficulty for 2 months. On the initial CT scan, there were two enhancing lesion in the suprasellar area and pineal gland which were completely disappeared with steroid therapy and three new lesions appeared on the follow-up CT and MRI studies in corpus callosum, third ventricle and left cerebral peduncle. The serial cytologic smears of cerebrospinal fluid and a stereotaxic biopsy tissue from the corpus callosum mass showed diffusely homogenous infiltration of neoplastic large noncleaved lymphocytes with focal perivascular arrangement. On the immunocytochemical stains, the reaction was negative for GFAP, positive for LCA and MB2, and negative for MT1. After radiation therapy, the masses completely disappeared on the follow-up CT scan and the patient was discharged free of all the clinical symptoms.
Original Articles
Application of Immunohistochemical Stain for Granulocytic Sarcoma.
Yeong Ju Woo, Chan Hwan Kim, Jong Eun Joo
Korean J Pathol. 1994;28(1):30-37.
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AbstractAbstract PDF
Granulocytic sarcoma is a rare localized tumor composed of granulocytic precusor cells. Granu-locytic sarcoma occurs in a variety of clinical conditions and it is often misdiagnosed histologically. Differential diagnosis frorh lymphoma or nonhematopoietic malignancies such as undifferentiated carcinoma or sarcoma is difficult in the routing histologic examination. An evaluation of clinical and histopathologic features was done on 4 cases of granulocytic sarcoma which were diagnosed at Pusan Paik Hospital from 1988 to 1992. During the period, 282 cases of myelogenous leukemia were diagnosed. Immunohistochemical reaction for lysozyme, myelopero-xidase, leukocyte common antigen, epthelial membrane antigen and cytokeratin was assessed comparing to lymphoma and undifferentiated carcinoma. The histologic features of the granulocytic sarcoma revealed thin nuclear membrane, fine chromatin pattern and one or two small nucleoli. It also often involved the vascular wall and infiltrated the native structures without destruction. Immunohistochemical stain revealed that all(4 cases) of granulocytic sarcoma showed diffuse and strong positivity for myeloperoxidase, and partial but strong positivity for lysozyme. One case of granulocytic sarcoma was negative and 3 cases revealed focal positive reaction for LCA, and all 4 cases was negative for cytokeratin and EMA. In summary, careful observation under light microscopy with immunohistochemical stain for myeloperoxidase, lysozyme, and LCA is helpful in the differential diagnosis of granulocytic sarcoma from malignant lymphoma and cytokeratin and EMA is useful for differential diagnosis from undifferentiated carcinoma.
Immunohistochemical Analysis of HLA-DR and Secretory Component Expression in Gastric Adenocarcinoma.
Ji Youn Bae, Soo Sang Sohn, Eun Sook Chang
Korean J Pathol. 1996;30(4):293-300.
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AbstractAbstract PDF
Sixty one cases of gastric adenocarcinoma were studied immunohistochemically for expression of HLA-DR and secretory component(SC) in order to analyze the relationship between expression of these in gastric cancer cells and the adjacent mucosa. Immunostaining was detected within the cytoplasm and on the cell memgrane. The rate of HLA-DR and SC expressions in cancer cells were 59.0% and 49.2%, respectively, and 52.5%/52.5% and 31.2%/50.8% the mucosa in adjacent/remote from the site of to cancer. The SC expression in the adjacent mucosa was lower than that of the remote mucosa(p=0.027). The HLA-DR expression in the cancer cells in the intestinal type of gastric adenocarcinoma(73.9%) was higher than that of the diffuse type(14.3%) and it was statistically significant(p=0.02). The presence of an increased amount of lymphoid infiltration in the gastric mucosa was closely related to the expression of HLA-DR and SC. Decreased or absent expression of SC at the transitional mucosal cells was possibly a result of exposure to genotoxic agents due to the lack of protective function of SC-IgA. From these results, one can postulate that the expression of HLA-DR and SC may play an important role in atleration in microenvironment with lymphoid infiltration.
Immunohistochemical Study of Primary Large Cell Undifferentiated Carcinoma of the Lung.
Hye Seung Han, Jeong Wook Seo, Eui Keun Ham
Korean J Pathol. 1996;30(5):417-426.
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AbstractAbstract PDF
We performed a histopathologic and immunohistochemical study of 23 cases of surgically resected large cell undifferentiated carcinoma(LCUC) of the lung. The relative incidence of LCUC was 7.6% among the total resected cases of primary lung cancer over 7 years(1987-1993). The mean age of the patients was 56 years and 21 cases were male. The mean size of the mass was 5 cm and 11 cases were located peripherally. According to the histologic features, LCUC could be divided into three groups: squamous cell carcinoma-like(6 cases), adenocarcinoma-like(13 cases), and small cell carcinoma-like(4 cases) groups. The histologic differences were related to the variations of the immunohistochemical properties, but there were no differences in prognosis among these groups. Immunoreactivity to cytokeratin(CAM 5.2) was demonstrated in 22/23(96%). Carcinoembryonic antigen was positive in 13/23(57%). Neuron specific enolase and chromogranin were positive in 11/23(48%) and 5/23(22%), respectively. Vimentin was seen in 11/23(48%). From these observations, we could subclassify them by their immunologic phenotypes; exocrine features in 6/23(26%), neuroendocrine(NE) features in 4/23(17%), both exocrine and NE phenotypes in 7/23(30%), and 6 cases(26%) showed neither phenotype. The group with NE features showed a worse prognosis(P<0.05) and immunoreactivity for vimentin was also related to a worse prognosis(P<0.05). These findings imply that the immunohistochemical properties of LCUC are closely related to the histopathologic features. The groups, subdivided by histology and immunoreactivity, showed no prognostic difference except for the NE differentiation and reaction for vimentin.
Immunocytochemical Characteristics of the Short-term cultured Mesothelial Cells.
Ho Jong Jeon, Mi Ja Lee, Mi Sook Lee, Yu Kyung Jeong, Young Mi Lee, Hyung Ho Choi
J Pathol Transl Med. 1995;6(2):106-115.
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AbstractAbstract PDF
Reactive human mesothelial cells were examined by immunocytochemical stain with intermediate filaments(cytokeratin [CK1, CK7, CK8, CK18, CD19/, vimentin, desmin, actin), epithelial membrane antigen, carcinoembryonic antigen(CEA), MHC class II antigen(HLA-DR), LeuM-1(CD15), alpha1-antitrypsin(ACT), alpha1-antichymotrypsin (ACHT), CD68(KP-1) and FcgammaRIII(CD16). The mesothelial cells were isolated from patients with liver cirrhosis and pleural effusion, and short-term cultured in RPMI 1640 media containing 10% heat inactivated fetal calf serum and 1% identical supernatant fluid of the patients' transudates. The results obtained are as follows. 1. The cultured-reactive mesothelial cells were positive for the protein of cytoskeleton such as cytokeratin and vimentin, but negative for desmin and actin. The resting mesothelial cells showed positive reactions for cytokeratin, but negative for vimentin, desmin and actin. 2. The primary antibodies to the cytokeratin were strongly reactive for CK1, CK8 and CK18 but negative for CK7 and CK19 in both reactive and resting mesothelial cells. 3. Resting mesothelial cells showed negative reactions for CEA, but strong positive reactions in cultured-reactive mesothelial cells. 4. The markers for the monocytes\histiocytes (CD11b, CD14, CD16, CD68, lysozyme and alpha1-antitrypsin and alpha1-antichymotrypsin) were nonreactive in resting mesothelial cells, but lysozyme and alpha1-antitrypsin were weakly reactive in reactive and proliferative mesothelial cells. 5. MHC Class II molecule(HLA-DR antigen) was negative in both resting and reactive mesothelial cells. These results suggest that the short-term cultured, reactive mesothelial cells show a newly aberrant expression of the vimentin and carcino-embryonic antigen. The reason of the aberrant expression of the intermediate filament and oncofetal antigen in reactive and proliferative mesothelial cells should be further evaluated.
Detection of HBV DNA in Needle Biopsied Paraffin Embedded Liver Tissues of Chronic Hepatitis B Patients by PCR: Comparison with Serological and Immunohistochemical Studies.
Hye Soo Lee, Kahng Yeul Oh, Joo Heon Kim, Yoon Jeong Kim, Sam Im Choi, Dong Geun Lee, Sang Ho Kim
Korean J Pathol. 1996;30(6):495-504.
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AbstractAbstract PDF
In this study, the prevalence of Hepatitis B virus(HBV) DNA in the needle biopsied paraffin embedded liver tissues of chronic hepatitis B patients by rapid nested PCR was examined. DNA was extracted by NaOH with boiling, and amplified by rapid air thermocycler with glass capillary tubes and nested PCR with two primer sets specific for the surface and the core genes of HBV. The PCR results were compared to that of serum HBeAg, serum HBV DNA by dot blot hybridization with a radioactive DNA probe, and tissue immunohistochemical (HBsAg/ HBcAg) studies. Among 44 patients with chronic hepatitis with serum HBsAg positivity, HBV DNA could be detected by PCR in 43 liver tissues (98%). This results were comparable to the positive rates of 94%(31/33) for serum HBV DNA, 80%(35/44) for serum HBeAg, and 59%(26/44) and 75%(33/44) for tissue HBsAg and HBcAg, respectively. The accordance rate between tissue PCR and serum DNA probe testing was 91%. The results indicate that HBV DNA detection by rapid nested PCR of paraffin embedded liver tissues by needle biopsy is a more sensitive method to detect the HBV DNA carrier than the serum HBeAg or tissue HBsAg/HBcAg status, and is well correlated with the result of serum HBV DNA probe testing. Therefore this method is a practical indicator for the diagnosis and replication status in retrospective analysis.
Pathologic Findings of Mitochondrial Myopathy.
Lucia Kim, Tai Seung Kim
Korean J Pathol. 2000;34(1):77-84.
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AbstractAbstract PDF
Mitochondrial myopathy (MM) has been applied to muscle disease in which mitochondria have abnormal structure, function or both. To characterize the pathologic findings of MM, we examined the ultrastructural and histochemical findings of 24 cases of MM. The ultrastructures of the MM were characterized by abnormal mitochondria in number (pleoconia) and size (megaconia), and showed predominant accumulation of mitochondria in the subsarcolemmal space of myofibers in all cases. Mitochondria contained abnormally shaped cristae (concentric form and gyriform) in 79% of cases. Paracrystalline inclusion which was known to be a characteristics of MM were seen only in 7 cases (29%). Electron dense deposits were more frequently found (77%) in abnormal mitochondria of chronic progressive external opthalmoplegia and Kearn-Sayre syndrome. But, other findings were not specific for the specific clinical entities. On succinate dehydrogenase (SDH) stain, ragged red fibers (RRF) showed more intense positivity than modified Gomori-trichrome stain and definite strong reactive products were present along the periphery of myofibers which showed normal findings on modified Gomori-trichrome stain. In conclusion, ultrastructural findings such as mitochondria showing pleoconia with megaconia, and bizarre shaped cristae may be helpful for the diagnosis of MM and SDH stain is more useful for identification of RRF than modified Gomori-trichrome stains.
An Immunohistochemical Study on the Distribution of Endotoxin.
Tae In Park, Jung Ja Park, Jyung Sik Kwak, In Soo Suh
Korean J Pathol. 1994;28(3):260-271.
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AbstractAbstract
This study was performed to investigate the distribution of endotoxin in various organs after intraperitoneal injection of E. coli homogenator(0111:B4, 3X10(9)cells/200g of body weight). Sprague-Dawley rats were intraperitoneally injected with E. coli homogenator and sacrificed 1 and 3 hours after injection. The lung, liver, and kidney were immunohistochemically stained with avidin-biotin complex method and observed by light and electron microscopy. On the light microscopy, granular deposits of reaction products of immunohistochemical stain were found on the cytoplasmic membrane of endothelial cells and some of parenchymal cells of all organs observed. Electron microscopic study revealed finely granular reaction products on the surface of endothelial cells and some of parenchymal cells. The pinocytotic vesicles of endothelial cells demonstrated reaction products in the early phase of experiment. The distribution of reaction products were prominent in the liver among three organs. The Kupffer cells showed the most sensitive and strongest positive reaction. The hepatocytes and endothelial cells revealed weak positive reaction 3 hours later. The alveolar macrophages of the lung were also positive from the early phase of endotoxemia, while the pneumocytes and alveolar septa demonstrated weakly positive reaction in the later phase. The capillary endothelium of the kidney revealed positive reaction from the early phase. According to above results, it is concluded that the endotoxin entered into the systemic circulation was captured in the liver and lung. And both mononuclear phagocytic system and endothelial cells could be activated or damaged by endotoxin.
A Study of beta 2-Microglobulin Expression in Uterine Cervical Epithelial Lesion.
Na Hye Myong, Eui Keun Ham
Korean J Pathol. 1991;25(5):436-445.
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AbstractAbstract
Beta-2-microglubulin(beta 2m), the invariable light chain of the histocompatibility antigen is present on the surfaces of most human nucleated cells. It has proved to be reduced or disappeared on the cell surfaces of variable skin cancers. Patterns of beta 2m stainability in normal uterus and of the loss in several cervical epithelial lesions were examined by immunohistochemical staining using rat monoclonal and rabbit polyclonal anti-beta 2m, repectively on fresh tissues of 13 cases and formalin-fixed paraffin-embedded tissues of 23 cases. To know patterns of loss of beta 2m stainability and measure its extent and degree, only fixed tissues were examined. Fresh uterine tissue showed beta 2m stainability present on the cell membranes of squamous epithelium, endocervical gland, and capillary endothelium. Of these, squamous epithelium of uterine cervix revealed most characteristic lace-like staining along the cell outlines. Paraffin-embedded 23 cases were classified as group I (6 normal conrol and metaplasia), II (5 mild and moderate dysplasia), III (6 severe dysplasia and carcinome in situ), and IV ( 6 microinvasive and invasive squamous cell carcinoma). Group 2-4 showed reduced beta 2m stainability when compared to group 1 that exhibited the similar stainability as fresh normal cervical epithelium. The reduction or less proved to be statistically significant(p-value<0.001) in group 3 and 4 except for group 2. In spite of being invasive cases, a few disclosed beta 2m positive cells mainly in well-differentiated areas. In sum, ABC immunohistochemical staining of beta 2m showed the tendency tend to decrease or disappear in uterine cervical epithelial lesions with premalignant or malignant change and rather to appear in some well-differentiated areas of malignant lesions.
Case Reports
Adenoid Basal Carcinoma Associated with Invasive Squamous Cell Carcinoma of Uterine Cervix: A case report.
Hyun Jung Kim, Dong Won Kim, So Young Jin, Dong Wha Lee
Korean J Pathol. 1996;30(8):739-741.
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AbstractAbstract PDF
Adenoid basal carcinoma of the uterine cervix is a rare neoplasm that accounts for less than 1% of cervical adenocarcinomas. Though it has been confused with adenoid cystic carcinoma, it is now distinctly recognized by better prognosis and different histologic and immunohistochemical findings. We have experienced a case of adenoid basal carcinoma associated with invasive squamous cell carcinoma of the uterine cervix in a 52-year-old woman. The tumor was composed of small, round to oval nests of basaloid cells with peripheral palisading. Some of the nests showed central cystic spaces, or cribriform pattern, and central squamous differentiation with cytological atypia. Invasive squamous cell carcinoma was located adjacent to the adenoid basal carcinoma without any transition between these two lesions. Immunohistochemically, the tumor cells disclosed positive staining for cytokeratin, but negative reaction for CEA, EMA, and S-100 protein.
Creutzfeldt-Jakob Disease: Histopathologic, Electron Microscopic and Immunohistochemical Studies of 2 Cases.
Duck Hwan Kim, Yeon Lim Suh, Duck Ryul Na, Won Kyu Joo, Yong Sun Kim
Korean J Pathol. 1996;30(9):830-838.
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AbstractAbstract PDF
Creutzfeldt-Jakob disease(CJD) is characterized clinically by rapidly progressive dementia with pyramidal, extrapyramidal, and cerebellar symptoms and signs, and histologically by spongiform change, neuronal loss and reactive gliosis. We have experienced 2 cases of CJD. Case 1 was a 36-year-old male who had suffered from myoclonus and cerebellar symptoms including sluggish speech, gait and balance disturbance. Case 2 was a 70-year-old female who had showed cognitive dysfunction, ataxic gait and disturbance of extraocular movement. Both patients, underwent brain biopsy.
Case
1 revealed marked cortical atrophy, 2mm in thickness, with neuronal loss and astrocytic proliferation extending into white matter. The spongiform change, made up of many small, usually rounded or oval, vacuoles was noted mainly in the neuropil. Case 2 revealed remarkable spongiform change throughout the cortex and cytoplasmic vacuoles compressing the nuclei of neuronal cells were numerous. Neuronal loss and gliosis were also found without considerable change in the white matter. On double immunostaining against GFAP and PrP(Prion Protein), there was a weak positive reaction for PrP in the perinuclear cytoplasm in case 1, and a strongly positive reaction in case 2. The electron microscopic examination showed numerous membrane-bound vacuoles in neuropil and perikarya of neurons. The majority of the vacuoles were multiseptated by thin membranous structures. They demonstrated curled, or disrupted membrane, that had foldings and protrusions into the vacuolar clear spaces. There were neither identifiable virus-like particles nor amyloid deposition.
Original Articles
Detection of Helicobacter pylori in Gastric and Duodenal Biopsy Specimens by Immunohistochemical Stain.
Jong Im Lee, Jung Ran Kim, Jung Ho Lee, Gyoung Yim Ha
Korean J Pathol. 1996;30(10):873-885.
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AbstractAbstract PDF
A large body of evidence indicates that Helicobacter pylori is involved in the pathogenesis of chronic gastritis and peptic ulcers. Several techniques are currently used for detecting H. pylori. Recently the immunohistochemical method was introduced for rapid detection of H. pylori. To compare the result of the immunohistochemical method with those obtained by microbiologic methods, we glean formalin fixed, paraffin embbeded gastric and duodenal biopsy specimens from 85 patients with upper gastrointestinal symptoms. We set fifty cases which H. pylori was cultivated and identified by Gram stain as Group I, and thirty-five cases without H. pylori in Gram stain and culture as Group II. The results were as follows. 1) The sensitivity and the specificity of immunohistochemical method were 94% and 80% compared with the microbiologic method. Positive and negative predictive value of the immunohistochemical method were respectively 87% and 90%. However, in seven cases of Group II, H. pylori were identified by immunohistichemical method. 2) Immunohistochemical staining exhibited bacteria that were present in the mucus layer, the surface of the gastric mucosa and metaplastic gastric epithelium in duodenum. With reference to the distribution and density of H. pylori in Group I and II, a significant correlation existed between microbiologic results and bacterial load of the biopsy specimen (p<0.01). 3) Chronic inflammation of gastric biopsies were seen in all 45 H. pylori-positive cases(100%) and 16 out of 19 H. pylori-negative cases(84%). The degree of chronic inflammation was more severe in positive cases than negative cases. Activity of inflammation was seen 98% of H. pylori-positive cases and 16% of H. pylori-negative cases. Intestinal metaplasia was seen 40% of H. pylori-positive cases and 58% of H. pylori-negative cases. Lymphoid follicles and aggregates were seen in 47%(27 cases) of H. pylori-positive cases. Among 47%, cases with lymphoid follicles were 9%(4 cases) and cases with lymphoid aggregates were 38%(17 cases). In H. pylori-negative cases, lymphoid follicles and aggregates were seen in 16%(3 cases). It is possible to obtain samples from most of the individuals who underwent the endoscopy in Korea. And this method is simple, rapid and sensitive. We conclude that the immunohistochemical method is another useful diagnostic tool for detection of Helicobacter pylori.
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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AbstractAbstract 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.
Expression of BrdU and C-Ha-ras in Experimentally Induced Enzyme Altered Foci of the Liver and Hepatocellular Carcinoma.
Myung Sook Kim, Woo Ho Kim, Yong Il Kim
Korean J Pathol. 1994;28(6):584-595.
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AbstractAbstract PDF
For sequential phenotypic changes including enzyme altered hepatocytic foci, hyperplastic nodules, hepatocellular adenomas and carcinomas were produced in Sprague-Dawley rats by Solt-Farber method (administration of diethylnitrosamine and acetylaminofluorene (AAF), and partial hepatectomy). The immunohistochemical expressions of glutathione S transferase P (GST-P) and bromodeoxyuridine (BrdU) were assessed for selective proliferative activity in the enzyme altered foci and the subsequently developed lesions by double immunohistochemical staining technique. Immunoreactive areas against GSTP gradually increase from early period of carciogenesis. BrdU labeling in such areas remained high during the first week. but decreased thereafter. BrdU labeling index remained low in the GSTP negative area throughout the experimental period. This suggests that cells in the enzyme altered foci keep away from the suppressor effect of AAF in contrast to the normal cells in which their growth are inhibited by AAF. BrdU labeling index remained very low in both hyperplastic nodule and adenoma which were prevalent during the mid-experimental period, but increase markedly in carcinoma. The long period of low BrdU labeling index seems to correspond to the "slowly growing step of persistent nodule" during hepatocarcinogenesis. The differentiation index, a ratio of S phase fraction between GSTP positive and negative areas, was low in adenoma-developing period and high in carcinoma-developing period. C-Ha-ras p21 was not expressed in foci of enzyme altered hepatocyte and hyperplasia, but highly positive in carcinoma. This indicates that the c-Ha-ras may involve the late step of hepatocarcinogenesis.
Detection of Mycobacterium tuberculosis DNA in Ethanol-Fixed and Papanicolaou Stained Archival Materials.
Tae Sook Hwang, In Seo Park, Hye Seung Han, Jee Young Han, Young Bae Kim
Korean J Pathol. 1998;32(8):603-607.
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AbstractAbstract
Granuloma is a chronic inflammatory process associated with non-infectious agents or infectious diseases such as tuberculosis. It is well known that AFB staining, which has been used to determine the etiology of the granulomatous inflammation, lacks both sensitivity and specificity. Due to the slow growth rate of most pathogenic mycobacteria, culturing of organisms can take up to eight weeks. It is not uncommon for specific therapy to be delayed, or for an inappropriate treatment be given to patients without mycobacterial infections or with infections caused by atypical mycobacteria. Determination of the causative agent in Papanicolaou stained cytology specimens gives pathologists even more difficulties when only necrotic material has been aspirated from the center of the granuloma. In recent years, the use of a polymerase chain reaction for the amplification of DNA has appeared promising in terms of speed, efficiency, sensitivity, and specificity. Since a polymerase chain reaction permits the sensitive genetic analysis of small amounts of tissue, it is ideally suited to the genetic analysis of cytologic specimens. A polymerase chain reaction is easily performed on unfixed and unstained cells, however, an analysis of ethanol fixed and Papanicolaou-stained archival smears has also been described. We have recently established a method to detect Mycobacterium tuberculosis organism by a nested polymerase chain reaction with primers in the insertion sequence IS 6110, using cellular digests of ethanol-fixed and Papanicolaou-stained archival specimens aspirated from the lymph nodes, lungs, thyroid, etc. Inhibitors present in Papanicolaou stained material was removed by destaining the slides with 0.5% HCl solution for 10-30 minutes. Eight out of ten cases which have shown the epithelioid granulomas revealed a positive reaction and four out of ten cases which have shown lymphohistiocytic cells in a necrotic background without any evidence of granuloma revealed a positive reaction. This study showed that it was possible to employ a polymerase chain reaction to detect Mycobacterium tuberculosis in Papanicolaou stained archival cytology specimens.
Case Report
Scleroma of the Larynx: A Case Report.
Hun Soo Kim, Seok Won Park, Jin Man Kim
Korean J Pathol. 2003;37(4):287-290.
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Scleroma of the larynx is a rare specific granulomatous disease and is usually presented as alaryngeal extension of a primary rhinoscleroma. We report an unusual case of laryngeal scleromain a 64-year-old female patient whose presented with progressive upper respiratory obstructivesymptoms lasted for 2 years. Symptoms were acutely exaggerated during the course of one month.On physical examination, the nasal mucosa was atrophic and crusted, and septal perforationwas noted. The fiberoptic laryngoscopy revealed a yellowish granulated epiglottic mass with adirty surface mimicking laryngeal cancer. Histological sectioning showed the characteristic featuresof scleroma including Mikulicz cells with scattered plasma cells and some neutrophils.Warthin-starry stains and electron microscopy examination showed numerous short rods insidethe cytoplasm of the Mikulicz cells. After the diagnosis, the patient underwent an emergency tracheostomyfollowed by long-term antibiotic treatment, and her symptoms have slowly improved.
Original Articles
PLC-gamma1 for Differentiating Adenocarcinoma from Reactive Mesothelial Cells in Effusions.
Woo Yeong Ju, Sung Sook Kim
J Pathol Transl Med. 1997;8(2):115-119.
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AbstractAbstract PDF
Cytologic diagnosis of reactive or malignant effusion is sometimes difficult. Espe- cially, differentiation of benign reactive mesothelial cells from malignant cells in body effusion is more difficult. Recently, immunohistochemistry has been used to diagnose difficult cases. Phospholipase C(PLC)-gamma 1 is one of the isoenzyme of the PLC which plays central role in signal transduction involving cellular growth, differentiation and transformation by phosphorylating many protein component. Increased expression of PLC-gamma 1 in human breast carcinoma, colorectal carcinoma and stomach cancers are reported. To evaluate the efficacy of positive PLC-gamma 1 immunostaining in the diagnosis of malignancy in effusions, paraffin-embedded cell blocks of pleural fluid and ascites from 10 patients(5 metastatic adenocarcinomas, and 5 reactive mesothelial cells) were immunostained with a monoclonal antibody to PLC-gamma 1. PLC-gamma 1 immuostained all the adenocarcinomas in cell block(5/5) with intense membrane pattern, however, none of the reactive mesothelial proliferations stained with the diagnostic membrane pattern. Thus, our study strongly supports the conclusion that PLC-gamma 1 immunopositivity is likely to become a useful adjunct for the diagnosis of malignancy in effusions.
Comparison of Ziehl-Neelsen Stain and TB-PCR on Detection of Mycobacterium tuberculosisin Formalin-fixed, Paraffin-embedded Tissues of Chronic Granulomatous Inflammation.
Min Sun Cho, Shi Nae Lee, Sun Hee Sung, Woon Sup Han
Korean J Pathol. 2003;37(6):379-383.
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AbstractAbstract PDF
BACKGROUND
TB-PCR is a faster and more sensitive method to detect mycobacterium than acid-fast bacilli (AFB) stain, which is laborious and time consuming. We compared the sensitivity and specificity of AFB stain and TB-PCR and examined the possibility of TB-PCR as a confirmative test without AFB stain in the diagnosis of tuberculosis.
METHODS
We performed Ziehl-Neelsen stain and nested PCR using a commercially available TB-PCR kit amplifying IS6110 sequence in 81 cases of paraffin-embedded tissues diagnosed as chronic granulomatous inflammation. In addition, we evaluated the morphology of granuloma and the presence of caseation necrosis.
RESULTS
Of the 81 cases studied, 22 (27.2%) and 40 (49.4%) were positive for AFB stain and TB-PCR, respectively. Of 49 cases accompanying caseation necrosis, 19 (38.8%) were AFB stain positive and 37 (75.5%) were TB-PCR positive; a result that is comparable with that of other reports. Of the 22 AFB-positive cases, 2 were TB-PCR negative.
CONCLUSION
TB-PCR is very helpful for the diagnosis of tuberculosis in routinely processed, formalin-fixed, paraffin-embedded tissue samples. Nevertheless, AFB stain should continue to be performed at the same time.
Effect of Lysodren(R) on the Ultrastructural Changes in the Rat Adrenal Corex: Immunohistochemical staining for anti-ACTH antibody on the adenohypophysis.
Ho Jong Chun, Hae Chang Cho, Hae Sook Song, Kyu Ho Park
Korean J Pathol. 1989;23(1):94-110.
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The toxicity and adrenostatic effect of o,p'-DDD, a derivative of the insecticidal DDT, on the adrenal cortex were well known. It known that the toxicity was based on the blocking of steroid biopsynthesis when cholesterol was converted to pregnenolone. Lysodren(R) was also known to be capable of producing a regression of adrenocortical carcinoma and its metastases, and this drug became one of useful choice for the treatment of unoperable adrenocortical carcinomas. Recently, fine structural effect of o,p'-DDD on the adrenocortical carcinoma show that the mitochondria is the primary target organelle. o,p'-DDD was dissolved in corn oil and it was orally administered for 28 days to investigate the ultrastructural effects of zona fasciculata of rat adrenal cortex. The results obtained were as follow: 1) The body weight was decreased after feeding o,p'-DDD. 2) Light microscopic examination showed no remarkable change except increased fine lipid droplets of zona fasciculata in group I (o,p'-DDD 75 mg/kg feeding). Moderately increased intracytoplasmic lipid droplets and pyknotic nuclei bearing membrane indentations were seen in group II (o,p'-DDD 150 mg/kg feeding). Large sized lipid droplet aggregates, pyknotic nuclei with severe nuclear membrane indentations and karyorrhexis in focal area were evident in group III. 3) Immunohistochemical staining for ACTH in pituitary gland showed increasing number of ACTH secretory cell and increasing intensity of staining property according to the dosage of o,p'-DDD. 4) Ultrastructural examination showed increased intracytoplasmic lipid droplets and mild increased peroxisome. There was no remarkable ultrastructural changes in mitochondria in group I. Moderately increased lipid droplets and clusters formation, compressed mitochondria, partial disappearance of mitochondrial cristae, increased peroxisome and nuclear membrane indentations were seen in group II. In group III, nuclear membrane showed prominent indentation. Numberous cytoplasmic vacuolation, double membrane ring in mitochondria, disappearance of mitochondrial cristae, myelin figure formation in mitochondrial matrix, and fatty changes in mitochondrial matrix were seen. These findings showed that the primary target organelle of attack by o,p'-DDD on zona fasciculata of adrenal gland in rat is mitochondria and it was developed from double ring formation in mitochondrial matrix.
A Study on Immunohistochemical Stain for S-100 Protein, HMB 45 and Proliferating Cell Nuclear Antigen(PCNA) of Spitz Nevus Compared with Benign Nevus and Malignant Melanoma.
Mee Yon Cho, Kwang Gil Lee, Myung Wook Kim
Korean J Pathol. 1992;26(6):552-560.
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The differential diagnosis between Spitz nevus and malignant melanoma is difficult due to similar histologic findings. To obtain the useful aids for the differential diagnosis between two diseases, we studied 13 cases of Spitz nevus, 8 benign nevi of compound and intradermal, and 9 melanomas of primary and metastatic, using the immunohistochemical stain for S-100 protein, HMB.45 and proliferating cell nuclear antigen(PCNA). The staining pattern and intensity of S-100 protein showed homogenously strong positive reactivity in all cases. The frequency of HMB.45 positive cell in Spitz nevus was significantly lower than that in melanoma. When compared with the usual compound and intradermal nevi, Spitz nevi showed more significantly positive reaction in the dermal component of nevus cells. The expression of PCNA was higher in melanoma than in Spitz nevus. The immunohistochemical stains for HMB.45 and PCNA are considered as a useful methods for differentiation between Spitz nevus and melanoma, while stain for S-100 protein is not helpful.

J Pathol Transl Med : Journal of Pathology and Translational Medicine
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