Journal of Pathology and Translational Medicine

Original Articles

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.

Citations

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Presurgery health influences outcomes following vertical sleeve gastrectomy in adolescents
Debi Swertfeger, Ahlee Kim, Hannah Sexmith, Maria E. Moreno‐Fernandez, W. Sean Davidson, Michael Helmrath, Todd Jenkins, Tsuyoshi Okura, Esmond Geh, Stavra A. Xanthakos, Sara Szabo, Takahisa Nakamura, Senad Divanovic, Amy Sanghavi Shah
Obesity.2024; 32(6): 1187. CrossRef
Immunobiotic Bacteria Attenuate Hepatic Fibrosis through the Modulation of Gut Microbiota and the Activation of Aryl‐Hydrocarbon Receptors Pathway in Non‐Alcoholic Steatohepatitis Mice
Paulraj Kanmani, Julio Villena, Soo‐kyoung Lim, Eun‐Ji Song, Young‐Do Nam, Hojun Kim
Molecular Nutrition & Food Research.2024;[Epub] CrossRef
Lipid nanoparticle-mediated hepatocyte delivery of siRNA and silibinin in metabolic dysfunction-associated steatotic liver disease
Yifu Lyu, Xiuyi Yang, Lei Yang, Jinyu Dai, Huanyu Qin, Yunuo Zhou, Yunan Huang, Yanmei Wang, Di Wu, Qindai Shuai, Qilong Li, Xiaofei Xin, Lifang Yin
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Enhanced hepatoprotective effects of empagliflozin and vitamin D dual therapy against metabolic dysfunction‐associated steatohepatitis in mice by boosted modulation of metabolic, oxidative stress, and inflammatory pathways
Wesam F. Farrash, Shakir Idris, Mohamed E. Elzubier, Elshiekh B. A. Khidir, Akhmed Aslam, Abdulrahman Mujalli, Riyad A. Almaimani, Ahmad A. Obaid, Mahmoud Z. El‐Readi, Mohammad A. Alobaidy, Afnan Salaka, Afnan M. Shakoori, Alaa M. Saleh, Faisal Minshawi,
International Journal of Experimental Pathology.2024; 105(6): 219. 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.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

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.

Citations

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Artificial intelligence scoring of liver biopsies in a phase II trial of semaglutide in nonalcoholic steatohepatitis
Vlad Ratziu, Sven Francque, Cynthia A. Behling, Vanja Cejvanovic, Helena Cortez-Pinto, Janani S. Iyer, Niels Krarup, Quang Le, Anne-Sophie Sejling, Dina Tiniakos, Stephen A. Harrison
Hepatology.2024; 80(1): 173. CrossRef
Classification of the Stages of Nonalcoholic Steatohepatitis via Federated General Visual Representation Learning
Mehmet Nergiz
International Journal of Imaging Systems and Technology.2024;[Epub] CrossRef
Outcome prediction in metabolic dysfunction‐associated steatotic liver disease using stain‐free digital pathological assessment
Timothy J. Kendall, Elaine Chng, Yayun Ren, Dean Tai, Gideon Ho, Jonathan A. Fallowfield
Liver International.2024; 44(10): 2511. CrossRef
Chronic polypharmacy, monotherapy, and deprescribing: Understanding complex effects on the hepatic proteome of aging mice
Kevin Winardi, John Mach, Matthew J. McKay, Mark P. Molloy, Sarah J. Mitchell, Michael R. MacArthur, Catriona McKenzie, David G. Le Couteur, Sarah N. Hilmer
Aging Cell.2024;[Epub] CrossRef
Non-alcoholic fatty liver disease: the pathologist’s perspective
Wei-Qiang Leow, Anthony Wing-Hung Chan, Paulo Giovanni L. Mendoza, Regina Lo, Kihan Yap, Haeryoung Kim
Clinical and Molecular Hepatology.2023; 29(Suppl): S302. CrossRef
CT-based Hounsfield unit values reflect the degree of steatohepatitis in patients with low-grade fatty liver disease
Ha Neul Kim, Hong Jae Jeon, Hei Gwon Choi, In Sun Kwon, Woo Sun Rou, Jeong Eun Lee, Tae Hee Lee, Seok Hyun Kim, Byung Seok Lee, Kyung Sook Shin, Hyun Jung Lee, Hyuk Soo Eun
BMC Gastroenterology.2023;[Epub] CrossRef
Artificial intelligence and deep learning: New tools for histopathological diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Yoshihisa Takahashi, Erdenetsogt Dungubat, Hiroyuki Kusano, Toshio Fukusato
Computational and Structural Biotechnology Journal.2023; 21: 2495. CrossRef
An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease
Timothy J. Kendall, Maria Jimenez-Ramos, Frances Turner, Prakash Ramachandran, Jessica Minnier, Michael D. McColgan, Masood Alam, Harriet Ellis, Donald R. Dunbar, Gabriele Kohnen, Prakash Konanahalli, Karin A. Oien, Lucia Bandiera, Filippo Menolascina, An
Nature Medicine.2023; 29(11): 2939. CrossRef
Improved pathology reporting in NAFLD/NASH for clinical trials
Caitlin Rose Langford, Marc H Goldinger, Darren Treanor, Clare McGenity, Jonathan R Dillman, Daniela S Allende, Robert Goldin, Elizabeth M Brunt, Kurt Zatloukal, Helmut Denk, Kenneth A Fleming
Journal of Clinical Pathology.2022; 75(2): 73. CrossRef
Standardizing the histological assessment of late posttransplantation biopsies from pediatric liver allograft recipients
Stefan G. Hübscher, Sandy Feng, Annette S. H. Gouw, Hironori Haga, Hyo Jeong Kang, Deirdre A. Kelly, Mina Komuta, Andrew Lesniak, Benjamin A. Popp, Henkjan J. Verkade, Eunsil Yu, Anthony J. Demetris
Liver Transplantation.2022; 28(9): 1475. CrossRef
Discordant pathological diagnosis of non‐alcoholic fatty liver disease: A prospective multicenter study
Takuya Kuwashiro, Hirokazu Takahashi, Hideyuki Hyogo, Yuji Ogawa, Kento Imajo, Masato Yoneda, Takashi Nakahara, Satoshi Oeda, Kenichi Tanaka, Yuichiro Amano, Shinji Ogawa, Atsushi Kawaguchi, Shinichi Aishima, Masayoshi Kage, Kazuaki Chayama, Atsushi Nakaj
JGH Open.2020; 4(3): 497. CrossRef
Obeticholic acid for the treatment of nonalcoholic steatohepatitis: Expectations and concerns
Stergios A. Polyzos, Jannis Kountouras, Christos S. Mantzoros
Metabolism.2020; 104: 154144. CrossRef
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
Journal of Pathology and Translational Medicine.2020; 54(3): 228. CrossRef
An Improved qFibrosis Algorithm for Precise Screening and Enrollment into Non-Alcoholic Steatohepatitis (NASH) Clinical Trials
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Lulu Sun, Jon N. Marsh, Matthew K. Matlock, Ling Chen, Joseph P. Gaut, Elizabeth M. Brunt, S. Joshua Swamidass, Ta-Chiang Liu
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Abdominal Radiology.2019; 44(9): 3058. CrossRef
Inhibition of mitochondrial fatty acid oxidation in drug-induced hepatic steatosis
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Liver Research.2019; 3(3-4): 157. CrossRef
Standardising the interpretation of liver biopsies in non‐alcoholic fatty liver disease clinical trials
Rish K. Pai, David E. Kleiner, John Hart, Oyedele A. Adeyi, Andrew D. Clouston, Cynthia A. Behling, Dhanpat Jain, Sanjay Kakar, Mayur Brahmania, Lawrence Burgart, Kenneth P. Batts, Mark A. Valasek, Michael S. Torbenson, Maha Guindi, Hanlin L. Wang, Veeral
Alimentary Pharmacology & Therapeutics.2019; 50(10): 1100. CrossRef
NAFLD Histology: a Critical Review and Comparison of Scoring Systems
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Current Hepatology Reports.2019; 18(4): 473. CrossRef
Hepatic sonic hedgehog protein expression measured by computer assisted morphometry significantly correlates with features of non-alcoholic steatohepatitis
Michael Estep, Rohini Mehta, Gary Bratthauer, Lakshmi Alaparthi, Fanny Monge, Simon Ali, Dinan Abdelatif, Zahra Younoszai, Maria Stepanova, Zachary D. Goodman, Zobair M. Younossi
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Moon Hyung Choi, Joon-Il Choi, Michael Yong Park, Sung Eun Rha, Soon Nam Oh, Seung Eun Jung, Jae Young Byun, Stephan Kannengiesser, Yohan Son
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Feasibility and agreement of stiffness measurements using gradient-echo and spin-echo MR elastography sequences in unselected patients undergoing liver MRI
Guilherme Moura Cunha, Kevin J Glaser, Anke Bergman, Rodrigo P Luz, Eduardo H de Figueiredo, Flavia Paiva Proença Lobo Lopes
The British Journal of Radiology.2018; : 20180126. CrossRef
Second harmonic generation microscopy provides accurate automated staging of liver fibrosis in patients with non-alcoholic fatty liver disease
Pik Eu Chang, George Boon Bee Goh, Wei Qiang Leow, Liang Shen, Kiat Hon Lim, Chee Kiat Tan, Manlio Vinciguerra
PLOS ONE.2018; 13(6): e0199166. CrossRef

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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Abstract 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.

Grading System for Gastric Epithelial Proliferative Diseases Standardized Guidelines proposed by Korean Study Group for Pathology of Digestive Diseases.: Hoguen Kim, So Young Jin, Ja June Jang, Woo Ho Kim, Sang Yong Song, Kyu Rae Kim, Eun Sil Yu, Hyung Sik Shin, Han Kyeom Kim, Jin Hee Sohn, Eun Kyung Hong, Youn Wha Kim, Jin Sook Jeong, Chang Jin Kim, Shin Eun Choi, In Suh Park, Chan Il Park, Yong Il Kim; Korean J Pathol. 1997;31(5):389-400.

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Abstract PDF: The assessment of epithelial changes in gastric mucosal biopsies has been one of the major problems caused by inconsistencies in and disagreements about nomenclature and interpretation. To resolve these issues, members of the Study Group for Pathology of Digestive Diseases reviewed microslides of 50 gastric lesions showing varying degrees of mucosal abnormality and reached the following consensus; 1) the proliferating gastric epithelium can be divided into hyperplastic and neoplastic; 2) the term "dysplasia" is reserved for the microscopic epithelial changes that are unequivocally neoplastic; 3) Biopsy specimens can be categorized as regenerative(negative for dysplasia), indefinite(questionable dysplasia), positive(positive for dysplasia) and overt carcinoma; 4) The positive category can be divided into two subgroups, high grade dysplasia and low grade dysplasia. Criteria for each grade are presented and discussed. We offer these guidelines for establishing the correct diagnosis of the gastric mucosal biopsy specimens and for prospective studies.

Expression of Cell Adhesion Molecules -CD44H and CD44v6- in Colorectal Carcinoma.: Dae Cheol Kim, Seo Hee Rha, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1998;32(9):655-662.

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Abstract: During tumor progression, a subset of cells acquires metastatic properties, presumably through a series of genetic alterations. As the result, cells detach from the primary tumor, penetrate the basement membrane and invade the adjacent structures including lymph and blood vessels. Loss of adhesive functions and gain of new adhesive functions are thought to play a crucial role in this metastatic cascade. Since tumor metastasis is the principle cause of death for cancer patients including colon cancer, there is a consensus that a search for tools that allow effective assessment of the metastatic potential of tumors is a prime goal for cancer research. An immunohistochemical study of cell adhesion molecules, CD44H and its variant CD44v6, was done to evaluate their relationship with known prognostic factors related to the progression and metastasis of colorectal carcinoma in 94 cases of colorectal carcinoma tissues. The results were as follows. The CD44H expression was detected in 90 (95.7%) and CD44v6 in 53 (56.4%) out of 94 cases of colorectal carcinoma, and the CD44H was overexpressed in tumor tissue more than in normal mucosa in 62% of the cases. The expression rates of both protein were not significantly correlated with age and sex of the patients, invasion depth, lymph node metastasis, tumor differentiation, and tumor site. The coexpression of CD44H and CD44v6 in tumor was significant (p<0.05). The above results suggest that overexpression of CD44H and loss of function to control the alternative splicing of CD44 mRNA resulting in CD44v6 expression and alteration of adhesive function are closely associated with tumorigenesis of the colorectum.

Case Report

Rosai-Dorfman Disease of the Nose and Salivary Gland: A case report.: Mee Sook Roh, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1999;33(12):1203-1206.

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Abstract PDF: Rosai-Dorfman disease (RDD) is a rare type of benign histiocytosis characterized histologically by intracellular engulfment of lymphocytes. Extranodal RDD may occur as a part of generalized process involving lymph nodes or may involve extranodal sites independent of the lymph node status. We have experienced a case of extranodal Rosai-Dorfman disease of the nose as an initial lesion prior to nodal involvement. The patient was a 20-year-old woman who complained of nasal obstruction for 4 years, remotely, and left submandibular mass for 3 months, recently. Histologically, the lesion taken from nasal cavity, submandibular gland and left upper jugular lymph node all showed an heavy infiltrate consisted of plasma cells, lymphocytes and sheets of macrophages with abundant pale cytoplasm, which replaced organ architecture. The associated focal fibrosis made it difficult to differentiate from inflammatory pseudotumor. Some macrophages demonstrated phagocytosis of lymphocytes, plasma cells and occasionally neutrophils. The macrophages were strongly positive for S-100 protein.

Original Article

Expression of pRb, p16, Cyclin D1 and Cyclin E in Infiltrating Duct Carcinoma of the Breast.: Hea Kyoung Hur, Mee Sook Roh, Jin Sook Jeong, Seo Hee Rha, Gi Yeong Huh, Sook Hee Hong; Korean J Pathol. 2001;35(5):416-423.

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Abstract PDF: BACKGROUND
Inactivation of the retinoblastoma protein (pRb) is a mechanism by which tumor cells can subdue normal growth control. Among the molecules involved in control of pRb phosphorylation, cyclin D1 and cyclin E have been found to be deregulated and overexpressed in various types of cancers.
METHODS
Immunohistochemical stains for pRb, p16, cyclin D1 and cyclin E were performed in 73 cases of infiltrating duct carcinomas of the breast. In addition to analysis of their expression rates, the relationships between their expressions and the clinicopathologic parameters were evaluated.
RESULTS
pRb, p16, cyclin D1 and cyclin E were positive in 64.7% (44 out of 68 cases), 24.6% (15 out of 61 cases), 43.8% (32 out of 73 cases) and 61.6% (45 out of 73 cases), respectively. Their expression rates were not significantly associated with clinicopathologic prognostic factors. 33 out of 38 cases with p16-negative reactions were pRb positive, while 10 out of 15 cases with pRb-negative reactions were p16 positive. There was a significant inverse relationship between pRb and p16 expressions (P<0.005). 25 out of 32 cases with cyclin E-positive reactions were cyclin D1-positive, and 25 out of 45 cases with cyclin D1-positive reactions were cyclin E-positive. A statistically significant association was observed between cyclin D1 and cyclin E expressions (P<0.05).
CONCLUSIONS
The main mechanism during tumorigenesis of breast carcinoma depends on the cyclin D1/p16/pRb pathway, but cyclin E might play a role in the absence of cyclin D1. The inverse correlation between the pRb and p16 expressions may represent one of the important mechanisms in tumorigenesis, as well.

Case Reports

Extrarenal Malignant Rhabdoid tumor: A Case Report.: Sang Yong Lee, Dae Cheol Kim, Seo Hee Rha, Sook Hee Hong, Tae Hun Kang, Young Ho Lee, Kyoung Jin Nam, Jin Sook Jeong; Korean J Cytopathol. 1996;7(1):69-74.

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Abstract PDF: Malignant rhabdoid tumor is a distinct renal tumor in the pediatric age group. It was originally described as a rhabdomyosarcomatoid variant of Wilms tumor. However, subsequent studies failed to confirm myogenous differentiation, so it is now considered to be a distinct and unique type of highly malignant tumor, histogenetically unrelated. Although extrarenal forms of this tumor are rare, several examples have been described in other sites, especially the liver, prostate, paravertebral area, urinary bladder and soft tissue. We experienced a case of malignant rhabdiod tumor located in the intraabdominal cavity in a 10 month-old boy. Smear of peritoneal fluid showed round, polygonal and irregular shaped cells with large nuclei, ample cytoplasm containing Jight pink "to purple cytoplasmic inclusions, and one or a few prominent nucleoli. Immunocytochemistry revealed positivity to cytokeratin, epithelial membrane antigen and vimentin, and negativity to desmin and neuron-specific enolase. These distinct cytologic appearance and immunophenotypes were most consistent with a diagnosis of extrarenal malignant rhabdoid tumor. The cytoplasmic inclusions were correlated with eosinophilic inclusions seen in histologic section and electron microscopy confirmed this interpretation, showing filamentous aggregations in the cytoplasms of the tumor cells.

Imprint Cytologic Feature of Pleuropulmonary Blastoma: A Case Report .: Mee Sook Roh, Ji Young Seo, Gi Yeong Huh, Pill Jo Choi, Sook Hee Hong, Jin Sook Jeong; Korean J Cytopathol. 2001;12(1):39-43.

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Abstract PDF: Pleuropulmonary blastoma (PPB) is an unusual intrathoracic blastoma presenting in childhood and characterized by a biphasic neoplastic population of undifferentiated, small round blastemal cells and larger spindle-shaped sarcomatous cells with entrapped benign epithelial-lined structures. We experienced the cytologic features of PPB in imprint smear from the pleural-based huge mass of the middle lobe of the right lung in a 4-year-old boy. The smears showed high cellularity composed of small ovoid blastemal elements and scattered spindle mesenchymal tumor cells. Lobectomy and pathologic investigation confirmed the diagnosis. PPB seems to be a tumor in which accurate diagnosis may be achieved by cytology if appropriate clinical information were given. Timely and accurate diagnosis of PPB by cytology paves the way for attempting preoperative treatment in future cases.

Original Articles

p53, Heat Shock Protein 70 and Topoisomerase II Expression in Gallbladder Carcinoma.: Dae Cheol Kim, Mee Sook Roh, Jin Sook Jeong; Korean J Pathol. 2006;40(6):432-438.

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Abstract PDF: BACKGROUND
The present study was designed to investigate the expression of p53, Heat Shock Protein 70 (HSP70), and Topoisomerase (Topo) II alpha in the preneoplastic lesions and carcinomas of the gallbladder (GB) and to assess the correlation between the expression of these proteins and the clinicopathologic parameters by performing immunohistochemistry.
METHODS
The immunohistochemical expressions of p53, HSP70 and Topo II alpha were evaluated in 38 gallbladder carcinomas and 3 adenomas. Fifteen CIS(s) and 8 dysplasias that were located adjacent to invasive carcinomas were also studied.
RESULTS
A p53 expression was identified in 22 (57.9%) of the 38 GB carcinomas, in 9 (64.3%) of 14 CISs, and in none of the 8 dysplasias and 3 adenomas. A HSP70 expression was found in 11 (29%) of the 38 carcinomas, in 11 (78.6%) of 14 CIS(s), and in 4 (57.2%) of 7 dysplasias. A Topo II alpha expression was present in 36 (94.7%) of the 38 carcinomas, in 13 (92.9%) of 14 CIS(s), in 7 (100%) of 7 dysplasias and in 3 (100%) of 3 adenomas. p53 overexpression was related to the T stage of the primary tumor, while HSP70 and Topo II alpha were not related to any of the clinicopathologic parameters.
CONCLUSION
p53 may be involved in GB carcinogenesis and in the progression of cancer. p53 may be also helpful for making the differential diagnosis between dysplasia and CIS. A further large study is needed to better elucidate the roles of HSP70 and Topo II alpha in GB carcinogenesis.

PDGF-R alpha Expression in Preneoplastic and Neoplastic Hepatocellular Lesions: A Rat Model N-nitrosomorpholine Stop Experiment.: Su Jin Kim, Kyoung Tae Kim, Jin Sook Jeong; Korean J Pathol. 2006;40(5):354-360.

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Abstract PDF: BACKGROUND
N-nitrosomorpholine (NNM) is a genotoxic hepatocarcinogenic agent. Preneoplastic and neoplastic hepatocyte lesions were induced in rats by oral exposure to NNM (200 mg/L) in a stop model experiment. Platelet-derived growth factor receptor (PDGF-R) is a tyrosine kinase receptor that works with PDGF, stimulating cellular growth and proliferation. The present study was designed to determine the role of PDGF-R alpha expression in hepatocellular neoplasms and precursors.
METHODS
Seventeen rats out of a starting number of 30 died. From the fifth week until the 24th week one or two rats were evaluated. Preneoplastic single cells or foci, foci of altered hepatocytes (FAH) hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were studied histologically, and the expressions of GSTp and PDGF-R alpha by immunohistochemistry.
RESULTS
At the fifth week, GSTp +single cells showed PDGF-R alpha expression (20.8+/-5.8%). At the sixth week, GSTp +single cells, located at periportal areas, co-expressed PDGF-R alpha (43.4+/-9.6%). Over the next several weeks periportal hepatocytes showed weaker PDGF-R alpha expression but no GSTp. GSTp+FAH, and all HCA, demonstrated no PDGF-R alpha expression. However, nine out of 10 (90%) HCC showed PDGF-R alpha expression.
CONCLUSIONS
These data showed that there were two peaks of PDGF-R alpha expression, and suggest that the earlier expression is related with the response to NNM-induced hepatocyte toxicity, and that the later response is associated to malignant transformation.

Case Reports

Nesal T-cell Lymphoma associated with Hemophagocytic Syndrome: A case report.: Mee Sook Roh, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1994;28(5):541-543.

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Abstract PDF: Peripheral T-cell lymphoma is the generic group given to a family of tumors composed of neoplastic lymphocytes with phenotypic features of peripheral T-cells. Certain peripheral T-cell lymphomas develop a hemophagocytic syndrome that mimics malignant histiocytosis, both clinically and pathologically. We experienced a case of nasal T-cell lymphoma, histologically mimicking malignant histiocytosis in a 40-year-old male. The chief complaints were nasal obstruction and intermittent mild fever. Mild anemia, elevated SGOT and SGPT, polyclonal gammophthy, and moderate hepatomegaly were present. Two weeks later was present an enlarged cervical lymph node. The biopsied nasal mass showed angiocentric and angiodestructive peripheral T-cell lymphoma withextensive necrosis and marked erythrophagocytosis by non-neoplastic histiocytes. Subsequently, cervical lymph node was biopsied, which showed peripheral T-cell ltmphoma with extensive necrosis and erythrophagocytosis as well. The atypical lymphoid cells revealed pan-T(+), but CD4(-) and CD8(-), whereas the reactive histiocytes showed lysozyme(+), immunohistochemistry.

Hamartoma Arising in the Urinary Bladder: A case report.: Young Bae Kim, Tae Sook Hwang, Byung Gon Park, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1993;27(3):283-286.

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Abstract PDF: Hamartoma of the bladder is quite a rare entity which is composed of a disorderly admixture of mature cellular elements normally present in the urinary bladder. There is a great controversy regarding the pathogenesis of this lesion. Whether it is a true hamartomatous lesion or metaplastic lesion developed secondary to the inflammatory process. Similar or identical lesions has often been given by other names such as florid examples of cystitis glandularis. We prefer to cell florid examples of cystitis glandularis rather than hamartoma when it was occurred in an old age higher then 50th decade. Here we report a case of hamartoma of the urinary bladder in 44 years old man. Cystoscopic examination revealed a papillary polypoid mass which was attached to the fundus of bladder by long stalk. The mass measured 1.5 cm in greatest diameter. It was composed of epithelial nests resembling von Brunn's nest, cystitis glandularis or cystitis cystica dispersed in a stroma rich in smooth muscle and fibrous tissue.

Original Articles

Expression of Cellular Oncogenes in Gastric Carcinoma Related with Its Histologic Subtype: Southern blot analysis and immunohistochemistry.: Jin Sook Jeong, In Hoo Kim; Korean J Pathol. 1992;26(6):543-551.

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Abstract PDF: To search biologic characteristics of gastric carcinoma, one of the most common cancer in Korea, the author examined the alterations in DNA level and the expression of Ha-ras gene and c-myc gene in 20 primary tumors. Amplification of c-Ha-ras DNA was detected in 4(40%) of 10 patients who showed histologic subtype of relatively differentiated adenocarcinoma, but rearrangement of c-Ha-ras DNA was absent. Neither augumentation nor deletion of the c-myc DNA was observed. Higher expression of the ras p21 in tumor cells was noted in more differentiated tumor cells rather than poorly differentiated cases. One mucinous carcinoma, two signet ring cell carcinomas and one papillary carcinoma did not disclose expression of p21. The expressions of c-myc oncogene product were variable and were not correspond to the expressions of ras p21. A tendency that poorly differentiated tumor cells had higher expression of c-myc oncogene was suggested.

Nesidioblastosis of the Pancreas.: Young Bae Kim, Jin Sook Jeong, Ahn Hong Choi; Korean J Pathol. 1992;26(5):484-489.

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Abstract PDF: The morphologic abnormalities of the endocrine pancreas that underlie persistent neonatal hyperinsulinemic hypoglycemia and are included under the heading "nesidioblastosis" appears to be heterogeneous. This characteristic morphologic finding is ductuloinsular complexes showing endocrine cells budding off the ductoepithelium and merging with adjacent endocrine cell clusters. A case of nesidioblastosis associated with hyperinsulinemic hypoglycemia occurred in a 6/365 year-old male neonate. Microscopic finding of near totally resected pancreas revealed irregular sized islets and ductuloinsular complexes, both of which contained hypertrophied B cells with a few mitosis. Because of persistent hypoglycemia after first operation, he received second operation 8 days after. This histologic finding was more severe comparative to that of first operation. According to these findings, the pathogenesis of nesidioblastosis may be congenital or developmental defect of a kind of compensatory mechanism by unknown stimuli to acquire persistent hypoglycemia.

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