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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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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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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Review

Pathologic Evaluation of Breast Cancer after Neoadjuvant Therapy: Cheol Keun Park, Woo-Hee Jung, Ja Seung Koo; J Pathol Transl Med. 2016;50(3):173-180. Published online April 11, 2016; DOI: https://doi.org/10.4132/jptm.2016.02.02

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Abstract PDF

Breast cancer, one of the most common cancers in women, has various treatment modalities. Neoadjuvant therapy (NAT) has been used in many clinical trials because it is easy to evaluate the treatment response to therapeutic agents in a short time period; consequently, NAT is currently a standard treatment modality for large-sized and locally advanced breast cancers, and its use in early-stage breast cancer is becoming more common. Thus, chances to encounter breast tissue from patients treated with NAT is increasing. However, systems for handling and evaluating such specimens have not been established. Several evaluation systems emphasize a multidisciplinary approach to increase the accuracy of breast cancer assessment. Thus, detailed and systematic evaluation of clinical, radiologic, and pathologic findings is important. In this review, we compare the major problems of each evaluation system and discuss important points for handling and evaluating NAT-treated breast specimens.

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Brief Case Reports

IgG4-Related Sclerosing Mesenteritis: Seok Joo Lee, Cheol Keun Park, Woo Ick Yang, Sang Kyum Kim; J Pathol Transl Med. 2016;50(4):309-311. Published online January 11, 2016; DOI: https://doi.org/10.4132/jptm.2015.12.03

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Soft Tissue Roasi-Dorfman Disease with Features of IgG4-Related Disease in a Patient with a History of Acute Myeloid Leukemia: Cheol Keun Park, Eun Kyung Kim, Ji-Ye Kim, Hayoung Woo, Mi Jang, Hyang Sook Jeong, Woo Ick Yang, Sang Kyum Kim; J Pathol Transl Med. 2016;50(3):246-249. Published online November 17, 2015; DOI: https://doi.org/10.4132/jptm.2015.10.08

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Case Study

Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination: Go Eun Bae, Nara Yoon, Ha Young Park, Sang Yun Ha, Junhun Cho, Yunkyung Lee, Kyoung-Mee Kim, Cheol Keun Park; Korean J Pathol. 2013;47(2):163-166. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.163

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Abstract PDF

Malakoplakia is a characteristic inflammatory condition, which is usually seen in the urogenital tract, and less frequently in the gastrointestinal tract. We present a case of colonic malakoplakia in an immunocompromised patient. A 55-year-old female visited the outpatient clinic for routine cancer surveillance. Her past medical history was significant for kidney transplantation 11 years ago, and she had been taking immunosuppressants. A colonoscopy revealed several depressed flat lesions and elevated polyps, which were 0.3 to 0.4 cm in size and accompanied by whitish exudates. A biopsy revealed an infiltration of histiocytes with ample granular eosinophilic cytoplasm, with some lymphocytes and plasma cells. Many histiocytes had the characteristic morphology, described as Michaelis-Gutmann bodies: one or several round basophilic structures of approximately 1 to 10 µm in size with some being laminated, some appearing homogeneous, and others having a dense central core with a targetoid appearance. These Michaelis-Gutmann bodies were positively stained on von Kossa stain, and were diagnostic for malakoplakia.

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Case Reports

Gastric Adenocarcinoma of Fundic Gland Type: Report of Three Cases: Eun Su Park, Young Eun Kim, Cheol Keun Park, Takashi Yao, Ryoji Kushima, Kyoung-Mee Kim; Korean J Pathol. 2012;46(3):287-291. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.287

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Abstract PDF

Recently, fundic gland type gastric adenocarcinoma (GA-FG) has been reported as a new entity. This report describes GA-FG among Koreans for the first time. From March 2008 to July 2010 we identified only three cases of GA-FG out of over 6,000 GAs resected by endoscopy or surgery. Cell differentiation by mucin proteins, pepsinogen-I, and H+/K+-ATPase was evaluated. All three cases were male patients and diagnosed as early stage GA. Histologically, GA-FGs were well-differentiated adenocarcinoma with pale gray-blue, basophilic columnar or cuboidal cells and mildly enlarged nuclei, resembling chief cells. All three cases were positive for pepsinogen-I and were classified as gastric mucin phenotype. Among three histologic subtypes of GA-FG, since tumors were mainly composed of chief cells, our three cases were classified as chief cell predominant type. In conclusion, GA-FG is very rare among Koreans and pepsinogen-I and MUC6 expression are typical immunohistochemical findings in GA-FG suggesting differentiation toward fundic glands.

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Hikari Asahara, Toshitatsu Takao, Yumiko Asahara, Masakyo Asahara, Douglas Motomura, Hiroya Sakaguchi, Tetsuya Yoshizaki, Nobuaki Ikezawa, Madoka Takao, Yoshinori Morita, Takashi Toyonaga, Masato Komatsu, Ryoji Kushima, Yuzo Kodama
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Esophageal Gland Duct Adenoma.: Yoonjung Kim, Yang Soon Park, Jei So Bang, Ji Yeon Kim, Young Hyeh Ko, Cheol Keun Park, Kyoung Mee Kim; Korean J Pathol. 2011;45:S45-S47.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S45

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Abstract PDF: Benign ductal or glandular neoplasms of the esophagus unrelated to Barrett esophagus are extremely rare. Only 9 cases have been reported in the English language literature. We now report a case of esophageal gland duct adenoma incidentally found in a 73-year-old man. A 0.8 cm-sized, polypoid submucosal lesion in the distal esophagus was removed. Histologically, the lesion was well circumscribed and consisted of several ducts or cysts with focal papillary configurations. Interstitial lymphocytic infiltration with germinal centers was also observed. The lining cells of ducts or cysts were composed of two layers: an inner intensely eosinophilic luminal duct cell layer and an outer myoepithelial cell layer that was accentuated by alpha-smooth muscle actin. There was no significant nuclear atypia or mitosis. Mucin production was occasionally observed in a few goblet cells. To the best of our knowledge, this is the first case of benign ductal or glandular neoplasm of the esophagus among Koreans.

Gastrointestinal Stromal Tumor of the Colon Mimicking Inflammatory Fibroid Polyp with a Novel 63 bp c-kit Deletion Mutation: A Case Report.: In Gu Do, Cheol Keun Park, Sung Hyun Yoon, John Goldblum, Kyoung Mee Kim; Korean J Pathol. 2009;43(4):374-377.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.374

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Abstract PDF: Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up. Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.

Original Articles

Helicobacter pylori Infection and Histopathological Features of Gastric Mucosa.: Gyung Hyuck Ko, Cheol Keun Park, Chun Sik Choi, Heung Bae Park, Jeong Hee Lee, Hye Jung Lee, Hyun Ju Kim, Kwang Ho Rhee; Korean J Pathol. 1996;30(3):199-209.

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Abstract PDF: A microscopic examination of 1,000 cases of gastroscopic biopsy specimens revealed that the prevalence and severity of chronic gastritis, neutrophilic infiltration, and Helicobacter pylori infection increased with advancing age until the age reached about 40, but they decreased thereafter in accordance with the increasing prevalence of intestinal metaplasia. The prevalence and severity of Helicobacter pylori infection, chronic gastritis, and neutrophilic infiltration were proportionately related to each other and to gastric peptic ulcer, but inversely related with intestinal metaplasia and gastric carcinoma. The results suggested that chronic gastritis and gastric peptic ulcer may be associated with Helicobacter pylori infection and that if these lesions persist, intestinal metaplasia may develop with decreased severity of chronic gastritis and Helicobacter pylori infection but, instead, increase of the risk of gastric carcinoma. And it is thought that the cause of the high incidence of gastric carcinoma in Korea may be related to the fact that chronic gastritis and Helicobacter pylori infection develop earlier in life and therefore the prevalence of intestinal metaplasia is higher in Korea than in other countries.

Correlation between p53 Immunohistochemical Expression, DNA Ploidy and Ki-67 Expression in Gastric Carcinoma.: Young Lyun Oh, Joung Ho Han, Young Hyeh Ko, Cheol Keun Park, Hwoe J Ree; Korean J Pathol. 1997;31(12):1264-1271.

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Abstract PDF: We examined the p53 protein overexpression and evaluated its correlation with pathobiological variables, including: (1) patient age, sex, tumor size, histological type and grade, invasion depth, vascular invasion, perineural invasion and lymph node status; (2) the Ki-67 labeling index in 100 gastric carcinomas; and (3) the DNA ploidy pattern, S phase fraction (SPF), and the proliferation index (PI) in 84 cases using flow cytometry. The positive rate of p53 staining was 48% and the p53 immunoreactivity was independent of variable clinicopathologic factors. No correlation was made between the Ki-67 labeling index with p53 immunostaining and DNA ploidy parameters. Aneuploidy rate was slightly higher in the p53 positive group (55.6%) than the p53 negative group (44.4%)(p=0.097). The mean values of SPF and PI were significantly higher in the p53 protein positive group. Aneuploidy was more often observed in the intestinal type (p=0.038), advanced gastric carcinoma (p=0.015) and lymph node positive group(p=0.039). The above results suggest that although the p53 protein overexpression has no significant correlation with pathological factors and the Ki-67 labeling index, it may play an important role in tumor cell proliferation. Since p53 protein overexpression was slightly higher in the aneuploidy group showing significant correlation with poor prognostic parameters, it is thought that re-evaluation of the p53 mutation by molecular biological study is needed.

Case Report

Metanephric Adenoma of the Kidney.: Yoon La Choi, Jung Won Lee, Jai Hyang Go, Cheol Keun Park; Korean J Pathol. 1998;32(1):72-75.

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Abstract PDF: Metanephric adenoma is a rare renal epithelial tumor. Its light microscopic features are very characteristic, and immunohistochemical and electron microscopic studies are not critical to the diagnosis. The literature indicate that, to date, the tumor has behaved in a benign fashion, and predominantly but not exclusively occurred in middle-aged women. It occurs in a wide range up to 11 cm and is usually an incidental finding but may be symptomatic with hematuria or flank pain. Recently, we have experienced a case of renal tumor showing distinctive adenomatous features, which is incidentally found in a 52-year-old female. This tumor is confined to the renal cortex and is well-circumscribed with a characteristic uniform and orderly proliferation of compact well-differentiated small tubules lined by bland oval cells with a very low level of mitotic activity. The term metanephric adenoma is appropriate for this tumor because it accurately describes its bland proliferation of tubules and reflects the embryonic architectural and cytological appearance of this proliferation. The pattern of the tumor, with its occasional papillary glomeruloid- like bodies and foci of elongated tubules, is reminiscent of the fetal metanephric kidney.

Original Articles

Expression of Cytokeratins 7 and 20 in Cholangiocarcinoma and Metastatic Colonic Adenocarcinoma of the Liver.: Cheol Keun Park, Mi Kyung Kim; Korean J Pathol. 1999;33(1):42-47.

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Abstract PDF: The distinction between cholangiocarcinoma (CC) and metastatic colonic adenocarcinoma of the liver (MCA) is often difficult, particularly in needle biopsy and fine-needle aspiration specimens, if histologic features alone are used. To examine the differences in the expressions of the cytokeratin (CK) 7 and 20 in the CCs and MCAs, we performed immunohistochemical studies on surgically resected 19 CCs and 23 MCAs. We used monoclonal antibodies against CK 7 and CK 20, and applied microwave antigen retrieval technique on formalin-fixed, paraffin-embedded tissue. We interpreted diffuse cytoplasmic reactivity found in > or =5% of tumor cells as positive. CCs showed CK 7+/CK 20- immunophenotype in 63%, CK 7+/CK 20+ in 32%, CK 7-/CK 20+ in 5%, and CK 7-/CK 20- in 0%. MCAs exhibited CK 7-/CK 20+ immunophenotype in 87%, CK 7+/CK 20+ in 9%, CK 7-/CK 20- in 4%, and CK 7+/CK 20- in 0%. CK 20-reactive cells in CCs were frequently columnar in shape (p<0.05). In conclusion, the CK 7/CK 20 immunophenotype was useful in the differentiation of CCs from MCAs: the CK 7+/CK 20- immunophenotype strongly suggested CCs, whereas the CK 7-/CK 20+ immunophenotype strongly suggested MCAs.

Histopathological Features of Endoscopic Biopsies in Ischemic Colitis.: Young Lyun Oh, Cheol Keun Park; Korean J Pathol. 1999;33(7):490-496.

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Abstract PDF: Ischemic colitis still remains largely underdiagnosed despite the fact that it is one of the most common disorders of the large bowel. The aims of the present study were to evaluate the variable histologic findings of ischemic colitis and to find out helpful histopathological features in diagnosis. Retrospective review of the clinical symptoms, underlying diseases, endoscopic findings of 23 patients, and the histologic features of 37 biopsies was done. We analyzed the significant pathologic features in the histologically diagnosed ischemic colitis group and compared the biopsy time between the histologically diagnosed ischemic colitis group and the non-diagnosed group. Comparison of the endoscopic biopsy time between the group that showed significant histologic features and the group that showed no significant histologic features was also done. The age of the patients ranged from 27 to 87 years. Most patients had abdominal pain, hematemesis, and melena. Endoscopic differential diagnoses included ischemic colitis, ulcerative colitis, infectious colitis, tuberculous colitis, Crohn's disease, and pseudomembranous colitis. Histologic features and diagnoses were also variable. The coagulative necrosis of mucosa and the epithelial desquamation were frequently detected in the group pathologically diagnosed as ischemic colitis. The most pathognomonic finding was coagulative necrosis of the mucosa that was almost always detected within seven days after the onset of clinical symptoms. Recognition of variable patterns of ischemic colitis in a biopsy specimen will direct the clinician to evaluate the vascular system. Early endoscopic biopsy is essential for the precise diagnosis of ischemic colitis.

Expression of Cytokeratin 7 and 20 in Periampullary Carcinomas.: Jong Sun Choi, Na Rae Kim, Geung Hwan Ahn, Cheol Keun Park; Korean J Pathol. 2000;34(1):34-38.

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Abstract PDF: The distinction of carcinomas involving periampullary region is often difficult, even in the surgically resected specimens. To examine the differences in the expressions of cytokeratin (CK) 7 and 20 in the periampullary carcinomas, we performed immunohistochemical studies on surgically resected 20 pancreatic duct adenocarcinomas (PDA), 13 distal bile duct adenocarcinomas (DBA), 10 duodenal adenocarcinomas (DA), and 18 ampulla of Vater adenocarcinomas (AVA). We analyzed the relationships between CK 7/CK 20 immunoprofile, and tumor cell differentiation and tumor size. We interpreted diffuse cytoplasmic reactivity found in > or =5% of tumor cells as positive. In the majority of cases, PDA were CK 7 /20 (95%), DBA CK 7 /20 (92.3%), DA either CK 7 /20 (40%) or CK 7 /20 (30%), AVA either CK 7 /20 (50%) or CK 7 /20 (44.4%). In DA, there was an increased CK 20 negativity in less differentiated (moderately or poorly differentiated) cases (p<0.05) and in larger (> or =5 cm) tumor size (p=0.049). In AVA, there was a tendency of increased CK 20 positivity in less differentiated cases (p=0.10). In conclusion, the CK 7/CK 20 immunophenotype is useful in the differentiation of periampullary carcinomas: the CK 7 /CK 20 immunophenotype strongly suggests DA or AVA, whereas the CK 7 /CK 20 immunophenotype suggests PDA or DBA.

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