Journal of Pathology and Translational Medicine

Review

Inflammatory bowel disease–associated intestinal fibrosis: Ji Min Park, Jeongseok Kim, Yoo Jin Lee, Sung Uk Bae, Hye Won Lee; J Pathol Transl Med. 2023;57(1):60-66. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.02

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Fibrosis is characterized by a proliferation of fibroblasts and excessive extracellular matrix following chronic inflammation, and this replacement of organ tissue with fibrotic tissue causes a loss of function. Inflammatory bowel disease (IBD) is a chronic inflammation of the gastrointestinal tract, and intestinal fibrosis is common in IBD patients, resulting in several complications that require surgery, such as a stricture or penetration. This review describes the pathogenesis and various factors involved in intestinal fibrosis in IBD, including cytokines, growth factors, epithelial-mesenchymal and endothelial-mesenchymal transitions, and gut microbiota. Furthermore, histopathologic findings and scoring systems used for stenosis in IBD are discussed, and differences in the fibrosis patterns of ulcerative colitis and Crohn’s disease are compared. Biomarkers and therapeutic agents targeting intestinal fibrosis are briefly mentioned at the end.

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Tim Kaden, Raquel Alonso‐Román, Johannes Stallhofer, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig
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Fibrosierende Erkrankungen im Gastrointestinaltrakt
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Resistance to apoptosis in complicated Crohn's disease: Relevance in ileal fibrosis
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Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease.2024; 1870(2): 166966. CrossRef
Characterization of patient-derived intestinal organoids for modelling fibrosis in Inflammatory Bowel Disease
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Inflammation Research.2024; 73(8): 1359. CrossRef
Food additives impair gut microbiota from healthy individuals and IBD patients in a colonic in vitro fermentation model
Irma Gonza, Elizabeth Goya-Jorge, Caroline Douny, Samiha Boutaleb, Bernard Taminiau, Georges Daube, Marie–Louise Scippo, Edouard Louis, Véronique Delcenserie
Food Research International.2024; 182: 114157. CrossRef
Epigenetic Regulation of EMP/EMT-Dependent Fibrosis
Margherita Sisto, Sabrina Lisi
International Journal of Molecular Sciences.2024; 25(5): 2775. CrossRef
Mechanisms and therapeutic research progress in intestinal fibrosis
Yanjiang Liu, Tao Zhang, Kejian Pan, He Wei
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Disease clearance in ulcerative colitis: A new therapeutic target for the future
Syed Adeel Hassan, Neeraj Kapur, Fahad Sheikh, Anam Fahad, Somia Jamal
World Journal of Gastroenterology.2024; 30(13): 1801. CrossRef
Urinary Hydroxyproline as an Inflammation-Independent Biomarker of Inflammatory Bowel Disease
Muriel Huss, Tanja Elger, Johanna Loibl, Arne Kandulski, Benedicta Binder, Petra Stoeckert, Patricia Mester, Martina Müller, Christa Buechler, Hauke Christian Tews
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Inflammatory Bowel Disease: Immune Function, Tissue Fibrosis and Current Therapies
Jesús Cosín-Roger
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The Diagnosis of Intestinal Fibrosis in Crohn’s Disease—Present and Future
Sara Jarmakiewicz-Czaja, Jolanta Gruszecka, Rafał Filip
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Role of gut microbiota in Crohn’s disease pathogenesis: Insights from fecal microbiota transplantation in mouse model
Qiang Wu, Lian-Wen Yuan, Li-Chao Yang, Ya-Wei Zhang, Heng-Chang Yao, Liang-Xin Peng, Bao-Jia Yao, Zhi-Xian Jiang
World Journal of Gastroenterology.2024; 30(31): 3689. CrossRef
Ultrasound of the bowel with a focus on IBD: the new best practice
Christina Merrill, Stephanie R. Wilson
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Unveiling the anti-inflammatory potential of 11β,13-dihydrolactucin for application in inflammatory bowel disease management
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Anis Hasnaoui, Racem Trigui, Mario Giuffrida
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Pathways Affected by Falcarinol-Type Polyacetylenes and Implications for Their Anti-Inflammatory Function and Potential in Cancer Chemoprevention
Ruyuf Alfurayhi, Lei Huang, Kirsten Brandt
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Time to eRAASe chronic inflammation: current advances and future perspectives on renin-angiotensin-aldosterone-system and chronic intestinal inflammation in dogs and humans
Romy M. Heilmann, Georg Csukovich, Iwan A. Burgener, Franziska Dengler
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Role of the epithelial barrier in intestinal fibrosis associated with inflammatory bowel disease: relevance of the epithelial-to mesenchymal transition
Dulce C. Macias-Ceja, M. Teresa Mendoza-Ballesteros, María Ortega-Albiach, M. Dolores Barrachina, Dolores Ortiz-Masià
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef

Original Articles

Polo-like kinase 4 as a potential predictive biomarker of chemoradioresistance in locally advanced rectal cancer: Hyunseung Oh, Soon Gu Kim, Sung Uk Bae, Sang Jun Byun, Shin Kim, Jae-Ho Lee, Ilseon Hwang, Sun Young Kwon, Hye Won Lee; J Pathol Transl Med. 2022;56(1):40-47. Published online November 16, 2021; DOI: https://doi.org/10.4132/jptm.2021.10.07

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Abstract PDF Supplementary Material: Background
Polo-like kinase 4 (PLK4) is a serine/threonine protein kinase located in the centriole of the chromosome during the cell cycle. PLK4 overexpression has been described in a variety of many common human epithelial tumors. Conversely, PLK4 acts as a haploinsufficient tumor suppressor in some situations, highlighting the importance of strict regulation of PLK4 expression, activity, and function. Meanwhile, the importance of chemoradiation resistance in rectal cancer is being emphasized more than ever. We aimed to analyze PLK4 expression and the tumor regression grade (TRG) in patients with rectal cancer, treated with chemoradiotherapy (CRT).
Methods
A retrospective study was conducted on 102 patients with rectal cancer who received preoperative CRT. Immunohistochemistry for PLK4 in paraffin-embedded tissue was performed from the biopsy and surgical specimens.
Results
We found significant association between high expression of PLK4 and poor response to neoadjuvant CRT (according to both Mandard and The Korean Society of Pathologists TRG systems) in the pre-CRT specimens. Other clinicopathologic parameters did not reveal any correlation with PLK4 expression.
Conclusions
This study revealed an association between high expression of PLK4 in the pre-CRT specimens and TRG. Our results indicated that PLK4 could potentially be a new predictor for CRT effect in patients with rectal cancer.

Association of PTTG1 expression with invasiveness of non-functioning pituitary adenomas: Su Jung Kum, Hye Won Lee, Soon Gu Kim, Hyungsik Park, Ilseon Hwang, Sang Pyo Kim; J Pathol Transl Med. 2022;56(1):22-31. Published online October 15, 2021; DOI: https://doi.org/10.4132/jptm.2021.08.31

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Abstract PDF

Background
Pituitary tumor transforming gene 1 (PTTG1), paired-like homeodomain 2 (PITX2), and galectin-3 have been widely studied as predictive biomarkers for various tumors and are involved in tumorigenesis and tumor progression. We evaluated the usefulness of PTTG1, PITX2, and galectin-3 as predictive biomarkers for invasive non-functioning pituitary adenomas (NFPAs) by determining the relationship between the expressions of these three proteins and the invasiveness of the NFPAs. We also investigated whether PTTG1, E-cadherin, and Ki-67, which are known to be related to each other, show a correlation with NFPA features.
Methods
A retrospective study was conducted on 87 patients with NPFAs who underwent surgical removal. The NFPAs were classified into three groups based on magnetic resonance imaging findings of suprasellar extension and cavernous sinus invasion. Immunohistochemical staining for PTTG1, PITX2, galectin-3, E-cadherin, and Ki-67 was performed on tissue microarrays.
Results
PTTG1 expression showed a statistically significant correlation with the invasiveness of NFPAs, whereas PITX2 and galectin-3 did not have a relationship with the invasiveness of NFPAs. Moreover, there was no association among PTTG1, E-cadherin, and Ki-67 expression.
Conclusions
PTTG1 has the potential to serve as a predictive biomarker for invasive NFPA. Furthermore, this study may serve as a reference for the development of PTTG1-targeted therapeutic agents.

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Takuro Hakata, Ichiro Yamauchi, Daisuke Kosugi, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Yohei Ueda, Toshihito Fujii, Daisuke Taura, Nobuya Inagaki
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Neoplasms and tumor-like lesions of the sellar region: imaging findings with correlation to pathology and 2021 WHO classification
Lorenzo Ugga, Raduan Ahmed Franca, Alessandra Scaravilli, Domenico Solari, Sirio Cocozza, Fabio Tortora, Luigi Maria Cavallo, Marialaura Del Basso De Caro, Andrea Elefante
Neuroradiology.2023; 65(4): 675. CrossRef
A comprehensive characterisation of phaeochromocytoma and paraganglioma tumours through histone protein profiling, DNA methylation and transcriptomic analysis genome wide
Prodromos Chatzikyriakou, Dimitria Brempou, Mark Quinn, Lauren Fishbein, Roberta Noberini, Ioannis N. Anastopoulos, Nicola Tufton, Eugenie S. Lim, Rupert Obholzer, Johnathan G. Hubbard, Mufaddal Moonim, Tiziana Bonaldi, Katherine L. Nathanson, Louise Izat
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Expression and clinical significance of Cathepsin K and MMPs in invasive non-functioning pituitary adenomas
Hongyan Liu, Saichun Zhang, Ting Wu, Zhaohui Lv, Jianming Ba, Weijun Gu, Yiming Mu
Frontiers in Oncology.2022;[Epub] CrossRef

Causes of necrotic features in fine-needle aspirates from cervical lymph nodes: Young Jin Seo, Hyeongchan Shin, Hye Won Lee, Hye Ra Jung; J Pathol Transl Med. 2021;55(1):60-67. Published online November 27, 2020; DOI: https://doi.org/10.4132/jptm.2020.09.28

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Abstract PDF

Background
Lymph node fine-needle aspiration (LN FNA) cytology indicates necrosis in various diseases. Dominant necrotic features make the diagnosis of underlying conditions very difficult.
Methods
We retrospectively reviewed 460 patients who underwent cervical LN aspiration cytology that revealed necrotic findings at Keimyung University Dongsan Hospital in Daegu, Korea, from 2003–2017. Each specimen was evaluated and analyzed in association with the clinical findings, biopsy findings, and/or other ancillary tests, including acid-fast bacilli staining and molecular testing for Mycobacterium tuberculosis.
Results
When necrotic features were noted upon cervical LN FNA cytology, the most common pathologic LN FNA category was necrosis alone (31.5%). The second most common category was granulomatous inflammation (31.3%), followed by Kikuchi disease (20.0%) and malignant neoplasm (8.7%). In cases where the cervical LN FNA revealed necrosis alone, the most common final diagnosis was tuberculosis. In young patients, Kikuchi disease should be considered as one cervical LN FNA category, while metastatic carcinoma should be suspected in older patients.
Conclusions
Even when necrosis alone is observed in LN FNA cytology, it is important to determine the cause through further evaluation.

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Case Studies

Amoebic Encephalitis Caused by Balamuthia mandrillaris: Su Jung Kum, Hye Won Lee, Hye Ra Jung, Misun Choe, Sang Pyo Kim; J Pathol Transl Med. 2019;53(5):327-331. Published online May 24, 2019; DOI: https://doi.org/10.4132/jptm.2019.05.14

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Abstract PDF

We present the case of a 71-year-old man who was diagnosed with amoebic encephalitis caused by Balamuthia mandrillaris. He had rheumatic arthritis for 30 years and had undergone continuous treatment with immunosuppressants. First, he complained of partial spasm from the left thigh to the left upper limb. Magnetic resonance imaging revealed multifocal enhancing nodules in the cortical and subcortical area of both cerebral hemispheres, which were suggestive of brain metastases. However, the patient developed fever with stuporous mentality and an open biopsy was performed immediately. Microscopically, numerous amoebic trophozoites, measuring 20 to 25 µm in size, with nuclei containing one to four nucleoli and some scattered cysts having a double-layered wall were noted in the background of hemorrhagic necrosis. Based on the microscopic findings, amoebic encephalitis caused by Balamuthia mandrillaris was diagnosed. The patient died on the 10th day after being admitted at the hospital. The diagnosis of amoebic encephalitis in the early stage is difficult for clinicians. Moreover, most cases undergo rapid deterioration, resulting in fatal consequences. In this report, we present the first case of B. mandrillaris amoebic encephalitis with fatal progression in a Korean patient.

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The role of plasma metagenomic sequencing in identification of Balamuthia mandrillaris encephalitis
Sarah Y. Edminster, Ryan W. Rebbe, Christopher Khatchadourian, Kyle M. Hurth, Anna J. Mathew, Julie Huss-Bawab, Mark S. Shiroishi, Devin Clark, Andrew P. Norgan, Susan M. Butler-Wu, Annie Hiniker
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Hooman Rahmati-Holasoo, Maryam Niyyati, Marziye Fatemi, Fatemeh Mahdavi Abhari, Sara Shokrpoor, Alireza Nassiri, Amin Marandi
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XueMei Fan, TianWen Chen, Hui Yang, Yue Gao, Yan Chen
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Diagnosis of Balamuthia mandrillaris Encephalitis by Thymine–Adenine Cloning Using Universal Eukaryotic Primers
Ju Yeong Kim, Myung-Hee Yi, Myungjun Kim, Joon-Sup Yeom, Hyun Dong Yoo, Seong Min Kim, Tai-Soon Yong
Annals of Laboratory Medicine.2022; 42(2): 196. CrossRef
Facial Balamuthia mandrillaris infection with neurological involvement in an immunocompetent child
Zhen Zhang, Jianying Liang, Ruoqu Wei, Xiaobo Feng, Lei Wang, Liuhui Wang, Piaoping Zhao, Hong Yu, Yan Gu, Zhirong Yao
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Subacute Balamuthia mandrillaris encephalitis in an immunocompetent patient diagnosed by next-generation sequencing
Changbo Xu, Xiaoyan Wu, Miaoqin Tan, Dongmei Wang, Shengnan Wang, Yongming Wu
Journal of International Medical Research.2022;[Epub] CrossRef
Distribution and Current State of Molecular Genetic Characterization in Pathogenic Free-Living Amoebae
Alejandro Otero-Ruiz, Leobardo Daniel Gonzalez-Zuñiga, Libia Zulema Rodriguez-Anaya, Luis Fernando Lares-Jiménez, Jose Reyes Gonzalez-Galaviz, Fernando Lares-Villa
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Lei Wang, Wenjing Cheng, Bing Li, Zhe Jian, Xianlong Qi, Dongjie Sun, Jian Gao, Xuetao Lu, Yi Yang, Kun Lin, Chuanlong Lu, Jiaxi Chen, Chunying Li, Gang Wang, Tianwen Gao
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Bile Granuloma Mimicking Peritoneal Seeding: A Case Report: Hasong Jeong, Hye Won Lee, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Yu Na Kang, Sang Pyo Kim, Misun Choe; J Pathol Transl Med. 2018;52(5):339-343. Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.06.02

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Abstract PDF

Laparoscopic cholecystectomy is a widely used treatment method for most cholelithiasis and is a relatively safe procedure. Foreign body granulomatous reaction to bile or gallstone spillage during laparoscopic cholecystectomy has rarely been reported. We report a case of bile granuloma after laparoscopic cholecystectomy, which mimicked peritoneal seeding. A 59-year-old Korean man presented with right upper quadrant pain. He underwent laparoscopic cholecystectomy for acute cholecystitis with cholelithiasis. Pathologic examination revealed an incidental adenocarcinoma invading the lamina propria with acute cholecystitis and cholelithiasis. After 3 months, follow-up abdominal computed tomography revealed a subhepatic nodule, which showed hypermetabolism on positron emission tomography–computed tomography. Suspecting localized peritoneal seeding, wedge resection of the liver, wedge resection of the transverse colon, and omentectomy were performed. Pathologic examination of the resected specimens revealed multiple bile granulomas. Awareness of bile granuloma mimicking malignancy is noteworthy for patient management to reduce unnecessary procedure during postoperative surveillance.

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Case Report

Sporadic Cutaneous Keratocyst without Nevoid Basal Cell Carcinoma Syndrome: Report of 1 Case.: Hye Won Lee, Ji Young Park, Sun Hee Kang, Misun Choe; Korean J Pathol. 2011;45(3):322-325.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.3.322

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Abstract PDF

A cutaneous keratocyst is very rare and is ordinarily associated with nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome. NBCCS is a rare autosomal-dominant disorder that results from the mutation in the patched homologue 1 (PTCH1) gene located on chromosome 9q22.3, with high penetrance and variable expressivity. NBCCS demonstrates multisystem manifestations such as multiple basal cell carcinomas in early age, jaw cysts and pits of the hands and feet. Cutaneous keratocysts are characteristically lined by festooned keratinized squamous epithelium with parakeratosis. The cystic wall contains neither granular cell layer nor skin appendages. To the best of our knowledge, only two cases of cutaneous keratocysts not associated with NBCCS have been reported to date. We report one another case of a histologically confirmed cutaneous keratocyst in a 50-year-old female without a family history and clinical features of NBCCS.

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Madelyn M. Class, Claire Rose Kissinger, Sidra Ibad, Aspen Trautz, Lisa Zhai, Farhaan Hafeez
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Original Article

Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma.: Ji Min Jeon, Hye Won Lee, Ji Young Park, Hye Ra Jung, Ilseon Hwang, Sun Young Kwon, Mi Sun Choe, Yu Na Kang, Sang Pyo Kim, Sang Sook Lee, Won Il Choi, Kun Young Kwon; Korean J Pathol. 2010;44(4):397-403.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.397

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Abstract PDF

BACKGROUND
Mucin (MUC)1 and MUC4 (MUC1, 4) are high molecular weight glycoproteins expressed in normal and malignant epithelial cells, and these expressions are related to the prognosis of some carcinomas. In non-small cell lung carcinoma (NSCLC), the relationship between MUC1, 4 expressions and their prognostic significance is not well known. We evaluated these relationships in a series of NSCLC: 1) between MUC1, 4 expression levels and histologic subtypes, and 2) between high expression of MUC1, 4 and their prognostic significance.
METHODS
We performed immunohistochemical staining for MUC1, 4 in paraffin-embedded tissues from 165 NSCLC cases arranged in a tissue microarray.
RESULTS
We found a significant correlation between MUC1, 4 expressions and NSCLC histologic subtypes (p < 0.05). High MUC1 expression was characteristic of adenocarcinoma. Low MUC1, 4 expressions were characteristic of squamous cell carcinoma. In adenocarcinoma, we found significant association between diffuse MUC1 expression and short patient survival (p = 0.005). In squamous cell carcinoma, diffuse MUC4 expression showed long patient survival trend (p = 0.128).
CONCLUSIONS
MUC1, 4 expression levels were significantly correlated with NSCLC histologic subtypes. Diffuse MUC1 expression was significantly associated with shortened survival in NSCLC patients, especially in adenocarcinoma.

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