Journal of Pathology and Translational Medicine

Original Article

A scoring system for the diagnosis of non-alcoholic steatohepatitis from liver biopsy: Kyoungbun Lee, Eun Sun Jung, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2020;54(3):228-236. Published online April 15, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.07

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Background
Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis.
Methods
Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system.
Results
Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH.
Conclusions
A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.

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Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología.2022; 45(8): 579. CrossRef
Changes in indications for outpatient percutaneous liver biopsy over 5 years: from hepatitis C to fatty liver disease
Marlone Cunha-Silva, Luíza D. Torres, Mariana F. Fernandes, Tirzah de M. Lopes Secundo, Marina C.G. Moreira, Ademar Yamanaka, Leonardo T. Monici, Larissa B. Eloy da Costa, Daniel F. Mazo, Tiago Sevá-Pereira
Gastroenterología y Hepatología (English Edition).2022; 45(8): 579. CrossRef

Review

Standardized Pathology Report for Colorectal Cancer, 2nd Edition: Baek-hui Kim, Joon Mee Kim, Gyeong Hoon Kang, Hee Jin Chang, Dong Wook Kang, Jung Ho Kim, Jeong Mo Bae, An Na Seo, Ho Sung Park, Yun Kyung Kang, Kyung-Hwa Lee, Mee Yon Cho, In-Gu Do, Hye Seung Lee, Hee Kyung Chang, Do Youn Park, Hyo Jeong Kang, Jin Hee Sohn, Mee Soo Chang, Eun Sun Jung, So-Young Jin, Eunsil Yu, Hye Seung Han, Youn Wha Kim; J Pathol Transl Med. 2020;54(1):1-19. Published online November 13, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.28

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Abstract PDF Supplementary Material

The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.

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Original Articles

Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients: Hyo Jeong Kang, Soon Auck Hong, Seak Hee Oh, Kyung Mo Kim, Han-Wook Yoo, Gu-Hwan Kim, Eunsil Yu; J Pathol Transl Med. 2019;53(4):253-260. Published online May 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.03

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Abstract PDF

Background
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive liver diseases that present as neonatal cholestasis. Little is known of this disease in Korea.
Methods
The records of five patients histologically diagnosed with PFIC, one with PFIC1 and four with PFIC2, by liver biopsy or transplant were reviewed, and ATP8B1 and ABCB11 mutation status was analyzed by direct DNA sequencing. Clinicopathological characteristics were correlated with genetic mutations.
Results
The first symptom in all patients was jaundice. Histologically, lobular cholestasis with bile plugs was the main finding in all patients, whereas diffuse or periportal cholestasis was identified only in patients with PFIC2. Giant cells and ballooning of hepatocytes were observed in three and three patients with PFIC2, respectively, but not in the patient with PFIC1. Immunostaining showed total loss of bile salt export pump in two patients with PFIC2 and focal loss in two. Lobular and portal based fibrosis were more advanced in PFIC2 than in PFIC1. ATP8B1 and ABCB11 mutations were identified in one PFIC1 and two PFIC2 patients, respectively. One PFIC1 and three PFIC2 patients underwent liver transplantation (LT). At age 7 months, one PFIC2 patient was diagnosed with concurrent hepatocellular carcinoma and infantile hemangioma in an explanted liver. The patient with PFIC1 developed steatohepatitis after LT. One patient showed recurrence of PFIC2 after 10 years and underwent LT.
Conclusions
PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.

Citations

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Progressive Familial Intrahepatic Cholestasis: A Descriptive Study in a Tertiary Care Center
Fahad I. Alsohaibani, Musthafa C. Peedikayil, Abdulaziz F. Alfadley, Mohamed K. Aboueissa, Faisal A. Abaalkhail, Saleh A. Alqahtani, Dirk Uhlmann
International Journal of Hepatology.2023; 2023: 1. CrossRef
Next-generation sequencing panel test results in pediatric patients with progressive familial intrahepatic cholestasis: a single-center experience
Ali TOPAK
The European Research Journal.2023; 9(6): 1438. CrossRef
Progressive Familial Intrahepatic Cholestasis: A Study in Children From a Liver Transplant Center in India
Sagar Mehta, Karunesh Kumar, Ravi Bhardwaj, Smita Malhotra, Neerav Goyal, Anupam Sibal
Journal of Clinical and Experimental Hepatology.2022; 12(2): 454. CrossRef
Liver transplantation in pediatric patients with progressive familial intrahepatic cholestasis: Single center experience of seven cases
Jung-Man Namgoong, Shin Hwang, Hyunhee Kwon, Suhyeon Ha, Kyung Mo Kim, Seak Hee Oh, Seung-Mo Hong
Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(1): 69. CrossRef
Liver Transplantation for Pediatric Hepatocellular Carcinoma: A Systematic Review
Christos D. Kakos, Ioannis A. Ziogas, Charikleia D. Demiri, Stepan M. Esagian, Konstantinos P. Economopoulos, Dimitrios Moris, Georgios Tsoulfas, Sophoclis P. Alexopoulos
Cancers.2022; 14(5): 1294. CrossRef
Morphology of transplanted liver in recurrent progressive familial intrahepatic cholestasis type 2
I. M. Iljinsky, N. P. Mozheiko, O. M. Tsirulnikova
Russian Journal of Transplantology and Artificial Organs.2021; 22(4): 192. CrossRef

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells: Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu; J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.01.14

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Abstract PDF Supplementary Material

Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

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Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
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Jiacheng Wu, Shan Qiao, Yien Xiang, Menying Cui, Xiaoxiao Yao, Ruixin Lin, Xuewen Zhang
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Yusuf A. Haggag, Mohamed Yasser, Murtaza M. Tambuwala, Suleiman S. El Tokhy, Mohammad Isreb, Ahmed A. Donia
International Journal of Pharmaceutics.2021; 600: 120532. CrossRef
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Christopher R. Starr, Marina S. Gorbatyuk
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Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
Areeba Anwar, Mohammad Ridwane Mungroo, Ayaz Anwar, William J. Sullivan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
ACS Infectious Diseases.2019; 5(12): 2039. CrossRef

C-reactive Protein Overexpression in the Background Liver of Hepatitis B Virus–Associated Hepatocellular Carcinoma Is a Prognostic Biomarker: Jin Ho Shin, Eunsil Yu, Eun Na Kim, Chong Jai Kim; J Pathol Transl Med. 2018;52(5):267-274. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.14

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Abstract PDF

Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC). Peripheral blood C-reactive protein (CRP) concentration and CRP overexpression in HCC cells are proven to be prognostic markers for HCC, but the significance of CRP expression in non-neoplastic hepatocytes, which are the primary origin of CRP, has not been studied. This study was conducted to determine the clinicopathologic significance of CRP immunoreactivity in the background liver of HBV-associated HCC.
Methods
CRP immunostaining was done on tissue microarrays of non-neoplastic liver tissues obtained from surgically resected, treatment-naïve HBV-associated HCCs (n = 156). The relationship between CRP immunoreactivity and other clinicopathologic parameters including cancer-specific survival was analyzed. CRP immunoreactivity was determined using a 4-tier grading system: grades 0, 1, 2, and 3.
Results
CRP was positive in 139 of 156 cases (89.1%) of non-neoplastic liver in patients with HCCs: grade 1 in 83 cases (53.2%); grade 2 in 50 cases (32.1%); and grade 3 in six cases (3.8%). The patients with diffuse CRP immunoreactivity (grade 3) had decreased cancer-specific survival (p = .031) and a tendency for shorter interval before early recurrence (p = .050). The degree of CRP immunoreactivity correlated with serum CRP concentration (p < .001).
Conclusions
CRP immunoreactivity in non-neoplastic liver is a novel biomarker for poor cancer-specific survival of HBV-associated HCC and correlates with serum CRP concentration.

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Case Study

Hepatocellular Carcinoma Arising in a Huge Hepatocellular Adenoma with Bone Marrow Metaplasia: Hyo Jeong Kang, Hui Jeong Jeong, So-Woon Kim, Eunsil Yu, Young-Joo Lee, So Yeon Kim, Jihun Kim; J Pathol Transl Med. 2018;52(4):226-231. Published online December 27, 2017; DOI: https://doi.org/10.4132/jptm.2017.11.12

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Abstract PDF

Hepatocellular adenoma (HCA) is the most common type of benign liver tumor, and its major complication is malignant transformation to hepatocellular carcinoma (HCC). Here, we report a case of HCC arising in HCA with bone marrow metaplasia in a 24-year-old Korean woman who presented with abdominal discomfort. A huge liver mass was found on abdominal ultrasonography. She underwent surgical hepatic resection, and the resected specimen was entirely involved by a 20-cm-sized tumor. Histological review revealed a well differentiated HCC arising from inflammatory HCA with β-catenin nuclear positivity and bone marrow metaplasia that contained hematopoietic cells. This case was unique because malignant transformation, inflammatory type HCA, β-catenin nuclear staining, and bone marrow metaplasia were simultaneously observed. Additionally, it should be noted that a large HCA with β-catenin activation can undergo malignant transformation and should be surgically resected in a timely manner.

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Original Articles

Loss of Progesterone Receptor Expression Is an Early Tumorigenesis Event Associated with Tumor Progression and Shorter Survival in Pancreatic Neuroendocrine Tumor Patients: Sung Joo Kim, Soyeon An, Jae Hoon Lee, Joo Young Kim, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2017;51(4):388-395. Published online June 8, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.19

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients.
Methods
To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival.
Results
PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses.
Conclusions
Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

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Venous invasion and lymphatic invasion are correlated with the postoperative prognosis of pancreatic neuroendocrine neoplasm
Sho Kiritani, Junichi Arita, Yuichiro Mihara, Rihito Nagata, Akihiko Ichida, Yoshikuni Kawaguchi, Takeaki Ishizawa, Nobuhisa Akamatsu, Junichi Kaneko, Kiyoshi Hasegawa
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Combined Infiltrative Macroscopic Growth Pattern and Infiltrative Microscopic Tumor Border Status Is a Novel Surrogate Marker of Poor Prognosis in Patients With Pancreatic Neuroendocrine Tumor
Bokyung Ahn, Joo Young Kim, Seung-Mo Hong
Archives of Pathology & Laboratory Medicine.2023; 147(1): 100. CrossRef
HORMONET: a phase II trial of tamoxifen for estrogen/progesterone receptor-positive neuroendocrine tumors
Milton J. Barros, Jonathan Strosberg, Taymeyah Al-Toubah, Victor Hugo F. de Jesus, Lais Durant, Celso A. Mello, Tiago C. Felismino, Louise De Brot, Rodrigo G. Taboada, Mauro D. Donadio, Rachel P. Riechelmann
Therapeutic Advances in Medical Oncology.2023;[Epub] CrossRef
Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors
Florian Viehweger, Lisa-Marie Tinger, David Dum, Natalia Gorbokon, Anne Menz, Ria Uhlig, Franziska Büscheck, Andreas M. Luebke, Claudia Hube-Magg, Andrea Hinsch, Doris Höflmayer, Christoph Fraune, Patrick Lebok, Sören Weidemann, Maximilian Lennartz, Frank
Analytical Cellular Pathology.2022; 2022: 1. CrossRef
Prognostic Nomograms to Predict Overall Survival and Cancer-Specific Survival of Patients With Pancreatic Neuroendocrine Tumors
Zuoli Song, Sumei Wang, Yujing Wu, Jinjuan Zhang, Shuye Liu
Pancreas.2021; 50(3): 414. CrossRef
Pancreatic High-Grade Neuroendocrine Neoplasms in the Korean Population: A Multicenter Study
Haeryoung Kim, Soyeon An, Kyoungbun Lee, Sangjeong Ahn, Do Youn Park, Jo-Heon Kim, Dong-Wook Kang, Min-Ju Kim, Mee Soo Chang, Eun Sun Jung, Joon Mee Kim, Yoon Jung Choi, So-Young Jin, Hee Kyung Chang, Mee-Yon Cho, Yun Kyung Kang, Myunghee Kang, Soomin Ahn
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Systemic distribution of progesterone receptor subtypes in human tissues
Teeranut Asavasupreechar, Ryoko Saito, Yasuhiro Miki, Dean P. Edwards, Viroj Boonyaratanakornkit, Hironobu Sasano
The Journal of Steroid Biochemistry and Molecular Biology.2020; 199: 105599. CrossRef
Progesteron receptor expression in insulin producing cells of neuroendocrine neoplasms
Tomoyoshi Tachibana, Atsuko Kasajima, Takeshi Aoki, Tomoaki Tabata, Keely McNamara, Samaneh Yazdani, Sato Satoko, Fumiyoshi Fujishima, Fuyuhiko Motoi, Michiaki Unno, Hironobu Sasano
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Lingaku Lee, Tetsuhide Ito, Robert T Jensen
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Immunohistochemistry, carcinomas of unknown primary, and incidence rates
Edward B. Stelow, Hadi Yaziji
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Carbonic anhydrase 9 expression in well-differentiated pancreatic neuroendocrine neoplasms might be associated with aggressive behavior and poor survival
Joo Young Kim, Sang Hwa Lee, Soyeon An, Sung Joo Kim, You-Na Sung, Ki-Byung Song, Dae Wook Hwang, Song Cheol Kim, Seung-Mo Hong
Virchows Archiv.2018; 472(5): 739. CrossRef
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Feiyang Wang, Zibo Meng, Shoukang Li, Yushun Zhang, Heshui Wu
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Estrogens modulate progesterone receptor expression and may contribute to progesterone-mediated apoptotic β-cell death
Viviane Abreu Nunes
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Interobserver Agreement on Pathologic Features of Liver Biopsy Tissue in Patients with Nonalcoholic Fatty Liver Disease: Eun Sun Jung, Kyoungbun Lee, Eunsil Yu, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Woo Sung Moon, Jin Sook Jeong, Cheol Keun Park, Jae-Bok Park, Dae Young Kang, Jin Hee Sohn, So-Young Jin; J Pathol Transl Med. 2016;50(3):190-196. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.01

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Abstract PDF

Background
The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement.
Methods
Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson’s trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics.
Results
Kappa values of the first review ranged from 0.0091–0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis.
Conclusions
More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.

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Review

Pathology-MRI Correlation of Hepatocarcinogenesis: Recent Update: Jimi Huh, Kyung Won Kim, Jihun Kim, Eunsil Yu; J Pathol Transl Med. 2015;49(3):218-229. Published online May 15, 2015; DOI: https://doi.org/10.4132/jptm.2015.04.15

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Abstract PDF

Understanding the important alterations during hepatocarcinogenesis as well as the characteristic magnetic resonance imaging (MRI) and histopathological features will be helpful for managing patients with chronic liver disease and hepatocellular carcinoma. Recent advances in MRI techniques, such as fat/iron quantification, diffusion-weighted images, and gadoxetic acid-enhanced MRI, have greatly enhanced our understanding of hepatocarcinogenesis.

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Original Articles

Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas: Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu; J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.19

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Abstract PDF

Background
C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

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Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors: Eun-Mi Son, Joo Young Kim, Soyeon An, Ki-Byung Song, Song Cheol Kim, Eunsil Yu, Seung-Mo Hong; J Pathol Transl Med. 2015;49(1):30-36. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.23

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Abstract PDF

Background
Pancreatic neuroendocrine tumors (PanNETs) are malignant endocrine neoplasms that present diverse clinical behaviors. Therefore, identification of biomarkers of PanNETs is important for stratification of the prognosis of PanNET patients. Recently, cytokeratin 19 (CK19) and KIT expression were reported to have prognostic significance in PanNET patients. Methods: To identify their prognostic significance, CK19 and KIT protein expression were assessed in 182 surgically resected PanNETs and compared with clinicopathologic factors. Results: Of 182 PanNETs cases, CK19 and KIT expression was noted in 97 (53.3%) and 16 (8.8%) cases, respectively. PanNET patients with CK19 expression had larger tumors (p=.006), higher World Health Organization (WHO) grade (p=.002) and pT classification (p<.001), increased distant metastasis (p=.004), and lymphovascular (p=.012) and perineural (p=.019) invasion. Similarly, those with KIT expression had larger tumors (p=.030), higher WHO grade (p=.001), advanced pT classification (p<.001), distant metastasis (p=.001), and lymphovascular invasion (p=.014). The 5-year survival rate for PanNET patients with KIT expression was significantly lower (62%) than that of patients without KIT expression (77%, p=.011), as determined by univariate but not by multivariate analyses. Conclusions: CK19 and KIT expression correlate with higher metastatic potential and advanced disease stage, and KIT expression is associated with worse survival in PanNET patients.

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Combined Infiltrative Macroscopic Growth Pattern and Infiltrative Microscopic Tumor Border Status Is a Novel Surrogate Marker of Poor Prognosis in Patients With Pancreatic Neuroendocrine Tumor
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Histopathological Causes of Late Liver Allograft Dysfunction: Analysis at a Single Institution: Eun Shin, Ji Hoon Kim, Eunsil Yu; Korean J Pathol. 2013;47(1):21-27. Published online February 25, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.1.21

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Abstract PDF

Background

We summarize our experience in the pathological diagnosis of late complications of liver transplantation (LT) to better understand the causes of late allograft dysfunction in a population mostly composed of patients with hepatitis B virus (HBV) infection.

Methods

We reviewed 361 post-transplant liver biopsies from 174 patients who underwent LT and first presented with liver function abnormalities 3 months post-procedure. The underlying diseases included HBV-associated liver disease (77%), toxic or alcoholic liver disease (10.3%), hepatitis C virus (HCV)-associated liver disease (8.6%), primary biliary cirrhosis (1.2%), primary sclerosing cholangitis (1.2%), and metabolic disease (1.7%).

Results

The three most common late complications were acute rejection (32.5%), recurrent disease (19.1%), and biliary complication (17.1%). Patients who underwent LT for HBV infection or for drug- or alcohol-related liver disease had a lower incidence of recurring disease than those who underwent transplantation for HCV infection. During post-transplantation months 3-12, acute rejection was the most common cause of allograft dysfunction and recurring disease was the leading cause for allograft dysfunction (p=0.039). The two primary causes of late allograft dysfunction have overlapping histological features, although acute rejection more frequently showed bile duct damage and vascular endothelialitis than recurring HBV infection, and recurring HBV infection had more frequent lobular activity and piecemeal necrosis.

Conclusions

The causes of late liver allograft dysfunction are closely associated with the original liver diseases and the period after LT. Careful attention is required for differential diagnosis between acute rejection and recurrent HBV.

Citations

Citations to this article as recorded by

Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection
Tatsuo Kanda, Naoki Matsumoto, Tomotaka Ishii, Shuhei Arima, Shinji Shibuya, Masayuki Honda, Reina Sasaki-Tanaka, Ryota Masuzaki, Shini Kanezawa, Masahiro Ogawa, Shintaro Yamazaki, Osamu Aramaki, Hirofumi Kogure, Yukiyasu Okamura
Reports.2022; 5(4): 49. CrossRef
Differences in risk factors for early-onset and late-onset biliary complications in liver transplant patients
Hsiu-Lung Fan, An-Chieh Feng, Meng-Hsing Ho, Shih-Ming Kuo, Wei-Chou Chang, Teng-Wei Chen
Journal of Medical Sciences.2015; 35(5): 201. CrossRef
Vitamin C exerts beneficial hepatoprotection against Concanavalin A-induced immunological hepatic injury in mice through inhibition of NF-κB signal pathway
Tao Liang, Xiaoyu Chen, Min Su, Hongqiu Chen, Guozhe Lu, Kun Liang
Food & Function.2014; 5(9): 2175. CrossRef

DPC4 Expression in the Small Intestinal Adenocarcinomas: Sun Jae Lee, Eunsil Yu, Young Kyung Bae, Kee-Taek Jang, Joon Mee Kim, Han-Ik Bae, Seung-Mo Hong, Ghil Suk Yoon; Korean J Pathol. 2012;46(5):415-422. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.415

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Abstract PDF

Background

Small intestinal adenocarcinomas (SACs) are rare malignancies of the alimentary tract with uncertain carcinogenesis.

Methods

We investigated the expression of deleted in pancreatic cancer 4 (DPC4) in 188 cases of surgically resected SACs, using tissue microarray technology.

Results

Twenty-four of the 188 tumors showed complete loss of Smad4/DPC4 expression in cytoplasm (score, 0; 12.8%). Eighty-four and 31 cases were moderately and strongly positive, respectively (score, 2 and 3; 44.7% and 16.5%, respectively) and 49 cases were focally or weakly stained (score, 1; 29.1%). Immunohistochemistry analysis showed that the expression of Smad4/DPC4 was related to an increased risk of lymphatic invasion but not to other clinicopathological features of the tumors (tumor location, differentiation, growth pattern, T stage, direct invasion, vascular invasion, and nodal metastasis). There was no significant association between Smad4/DPC4 expression and patient survival.

Conclusions

The present research is the first study to evaluate Smad4/DPC4 expression in a large sample of SACs with clinicopathologic correlation. Future studies should focus on the immunohistochemical and molecular characteristics of SACs to clarify their tumorigenesis.

Citations

Citations to this article as recorded by

American Registry of Pathology Expert Opinions: Evaluation of poorly differentiated malignant neoplasms on limited samples - Gastrointestinal mucosal biopsies
Andrew M. Bellizzi, Elizabeth A. Montgomery, Jason L. Hornick
Annals of Diagnostic Pathology.2020; 44: 151419. CrossRef

Clinicopathologic Features of Q Fever Patients with Acute Hepatitis: Miji Lee, Jae Jeong Jang, Yang Soo Kim, Sang-Oh Lee, Sang-Ho Choi, Sung-Han Kim, Eunsil Yu; Korean J Pathol. 2012;46(1):10-14. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.10

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Abstract PDF

Background

Q fever caused by Coxiella burnetii presents with diverse clinical and pathological features including subclinical or cholestatic hepatitis. However, the pathological features of liver biopsies from patients with Q fever have not been well described.

Methods

Clinical features and pathological findings of liver biopsies were reviewed in seven cases of Q fever that were confirmed by serological, microbiological, or molecular tests.

Results

All cases presented with fever. Liver enzymes were mildly elevated except one case with marked hyperbilirubinemia. Characteristic fibrin ring granulomas were present in three cases, epithelioid granulomas with eosinophilic infiltration in two cases, extensive extravasated fibrins without ring configuration mimicking necrotizing granuloma in one case, and acute cholangitis without granuloma in one case. All cases were treated with antibiotics for 20 days. Six cases were completely cured, but one suffered from multiorgan failure.

Conclusions

C. burnetii infection is uncommon, but should always be considered in patients with acute hepatitis and fever. Because variable-sized circumferential or radiating fibrin deposition was a consistent feature of the present cases, Q fever can be strongly suggested by pathological features and confirmed by serological and/or molecular tests.

Citations

Citations to this article as recorded by

(Seltene) infektiöse Hepatitiden als wichtige Differenzialdiagnose der unklaren Hepatopathie
Michael Wührl, Marc Ringelhan, Ursula Ehmer, Jochen Schneider, Juliane Kager, Tobias Lahmer, Anna Schneider, Wilko Weichert, Carolin Mogler
Die Pathologie.2023; 44(1): 53. CrossRef
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Frontiers in Veterinary Science.2023;[Epub] CrossRef
The First Case of Coxiella Burnetti Infection Detected Through Bone Marrow Biopsy in Vietnam
Do Thi Vinh An, Bui Thi Viet Ha, Dao Xuan Co, Vu Minh Tam, Le Thi Diem Tuyet, Vu Van Truong
Clinical Pathology.2022; 15: 2632010X2210963. CrossRef
Pathological study and molecular detection of zoonotic diseases in small ruminants at slaughter houses in Mymensingh, Bangladesh
Nazneen Sultana, Munmun Pervin, Sajeda Sultana, Mahmuda Islam, Moutuza Mostaree, Mohammad Abu Hadi Noor Ali Khan
Veterinary World.2022; : 2119. CrossRef
The First Report of Coxiella burnetii as a Potential Neglected Pathogen of Acute Hepatitis of Unknown Causes in Egypt
Mohamed A. El-Mokhtar, Ibrahim M. Sayed, Ayat M. Kamel, Ahmed Atef Mesalam, Elsayed A. Elgohary, Khaled Abo bakr Khalaf, Sara Adel, Azza Abo Elfadl, Walaa A. Khalifa, Haidi Karam-Allah Ramadan
Microorganisms.2022; 10(11): 2168. CrossRef
A case of coexistent acute severe alcoholic and Q fever hepatitis: The useful contribution of repeated liver biopsies
Zampaglione Lucia, Bornand Aurélie , Goossens Nicolas , Ramer Lucas , Magini Giulia , Ongaro Marie , Cerny Andreas , Rubbia-Brandt Laura , Jean-Louis Frossard, Spahr Laurent
Annals of Clinical Gastroenterology and Hepatology.2022; 6(1): 034. CrossRef
Q-fever associated granulomatous hepatitis
Nicolas Dauby, Maria Gomez Galdon, Isabel Montesinos, Marjan Van Esbroeck, Thomas Sersté
International Journal of Infectious Diseases.2020; 95: 113. CrossRef
Pathologic changes and immune responses against Coxiella burnetii in mice following infection via non-invasive intratracheal inoculation
Xueyuan Hu, Yonghui Yu, Junxia Feng, Mengjiao Fu, Lupeng Dai, Zhiyu Lu, Wenbo Luo, Jinglin Wang, Dongsheng Zhou, Xiaolu Xiong, Bohai Wen, Baohua Zhao, Jun Jiao, Daniel E. Voth
PLOS ONE.2019; 14(12): e0225671. CrossRef
Fibrin Ring Granulomas in Checkpoint Inhibitor-induced Hepatitis
Jamie Everett, Amitabh Srivastava, Joseph Misdraji
American Journal of Surgical Pathology.2017; 41(1): 134. CrossRef
Clinical and Genetic Features ofCoxiella burnetiiin a Patient with an Acute Febrile Illness in Korea
Seung Hun Lee, Jung Yeon Heo, Hae Kyung Lee, Yeong Seon Lee, Hye Won Jeong, Seon Do Hwang
Journal of Korean Medical Science.2017; 32(6): 1038. CrossRef
Q Fever Presented as a Large Retroperitoneal Pseudotumoral Mass
Behdokht Nowroozizadeh, Negar Haghighi Mehmandari, Nicolas Gallegos, Mari Perez-Rosendahl, Di Lu
Case Reports in Pathology.2017; 2017: 1. CrossRef
From Q Fever to Coxiella burnetii Infection: a Paradigm Change
Carole Eldin, Cléa Mélenotte, Oleg Mediannikov, Eric Ghigo, Matthieu Million, Sophie Edouard, Jean-Louis Mege, Max Maurin, Didier Raoult
Clinical Microbiology Reviews.2017; 30(1): 115. CrossRef
Prolonged Pyrexia and Hepatitis: Q fever
Caitlin Dugdale, Brian Chow, Evgeny Yakirevich, Erna Kojic, Bettina Knoll
The American Journal of Medicine.2014; 127(10): 928. CrossRef

Case Report

Clinicopathologic Analysis of the Liver Explant with Severe Hepatitis A Virus Infection.: Joo Young Kim, Sung Gyu Lee, Shin Hwang, Ji Hoon Kim, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2011;45:S48-S52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S48

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Abstract PDF: The incidence of severe hepatitis A virus (HAV) infection has been increasing. However, clinicopathologic features of severe HAV infection that lead to liver transplantation (LT) have not been reported in Korea. We retrieved 16 LT cases with HAV infection during the last 3 years at Asan Medical Center, Seoul, Korea. Fifteen cases progressed to hepatic encephalopathy. Thirteen cases survived with or without complications, and three patients died of sepsis. The explanted liver showed massive or zonal necrosis with moderate to severe cholestasis. The zonal distribution of necrosis was frequently associated with endothelialitis of portal and/or central veins. Degenerative changes of hepatocytes were various in degree and distribution. Viral inclusions were suspected in two cases. Although HAV infection is usually confirmed by serological tests, significant venulitis of central and/or portal veins and viral inclusions, which are rarely observed, can suggest an HAV infection as a cause of massive hepatic necrosis of unknown mechanism.

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