Journal of Pathology and Translational Medicine

Original Articles

Clinicopathologic significance of the delta-like ligand 4, vascular endothelial growth factor, and hypoxia-inducible factor-2α in gallbladder cancer: Sujin Park, Junsik Kim, Woncheol Jang, Kyoung-Mee Kim, Kee-Taek Jang; J Pathol Transl Med. 2023;57(2):113-122. Published online March 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.02.01

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Background
Gallbladder cancer (GBC) is usually detected in advanced stages with a low 5-year survival rate. Delta-like ligand 4 (DLL4), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-2alpha (HIF2α) have been studied for their role in tumorigenesis and potential for therapeutic target, and multiple clinical trials of the agents targeting them are ongoing. We investigated the expression of these markers in surgically resected GBC and tried to reveal their association with the clinicopathologic features, mutual correlation of their expression, and prognosis of the GBC patients by their expression.
Methods
We constructed the tissue microarray blocks of 99 surgically resected GBC specimens and performed immunohistochemistry of DLL4, VEGF, and HIF2α. We used the quantitative digital image analysis to evaluate DLL4 and VEGF expression, while the expression of HIF2α was scored manually.
Results
The expression of VEGF and HIF2α showed a significant trend with tumor differentiation (p= .028 and p= .006, respectively). We found that the high DLL4 and VEGF expression were significantly correlated with lymph node metastasis (p= .047, both). The expression of VEGF and HIF2α were significantly correlated (p < .001). The GBC patients with low HIF2α expression showed shorter recurrence-free survival than those with high HIF2α expression.
Conclusions
This study suggested the possibility of the usage of DLL4 and VEGF to predict the lymph node metastasis and the possibility of VEGF and HIF2α to predict the expression level mutually. Further studies may be needed to validate our study results and eventually accelerate the introduction of the targeted therapy in GBC.

Citations

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Identification of Key Immune Infiltration Related Genes Involved in Aortic Dissection Using Bioinformatic Analyses and Experimental Verification
Lin Zheng, Yusi Yang, Jie Liu, Tianliang Zhao, Xin Zhang, Lihua Chen
Journal of Inflammation Research.2024; Volume 17: 2119. CrossRef

Programmed death-ligand 1 expression and its correlation with clinicopathological parameters in gallbladder cancer: Ji Hye Kim, Kyungbin Kim, Misung Kim, Young Min Kim, Jae Hee Suh, Hee Jeong Cha, Hye Jeong Choi; J Pathol Transl Med. 2020;54(2):154-164. Published online February 10, 2020; DOI: https://doi.org/10.4132/jptm.2019.11.13

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Abstract PDF

Background
Immunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).
Methods
We investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.
Results
PD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).
Conclusions
The expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.

Citations

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Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis
Giorgio Frega, Fernando P. Cossio, Jesus M. Banales, Vincenzo Cardinale, Rocio I. R. Macias, Chiara Braconi, Angela Lamarca
Cells.2023; 12(16): 2098. CrossRef
Gallbladder carcinomas: review and updates on morphology, immunohistochemistry, and staging
Whayoung Lee, Vishal S. Chandan
Human Pathology.2023; 132: 149. CrossRef
Prognostic Relevance of PDL1 and CA19-9 Expression in Gallbladder Cancer vs. Inflammatory Lesions
Neetu Rawal, Supriya Awasthi, Nihar Ranjan Dash, Sunil Kumar, Prasenjit Das, Amar Ranjan, Anita Chopra, Maroof Ahmad Khan, Sundeep Saluja, Showket Hussain, Pranay Tanwar
Current Oncology.2023; 30(2): 1571. CrossRef
Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer
Ishita Ghosh, Ruma Dey Ghosh, Soma Mukhopadhyay
World Journal of Gastrointestinal Oncology.2023; 15(12): 2053. CrossRef
CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer
Lu Cao, Kim R. Bridle, Ritu Shrestha, Prashanth Prithviraj, Darrell H. G. Crawford, Aparna Jayachandran
International Journal of Molecular Sciences.2022; 23(3): 1565. CrossRef
Evolving Role of Immunotherapy in Advanced Biliary Tract Cancers
Sandra Kang, Bassel F. El-Rayes, Mehmet Akce
Cancers.2022; 14(7): 1748. CrossRef
Novel immune scoring dynamic nomograms based on B7-H3, B7-H4, and HHLA2: Potential prediction in survival and immunotherapeutic efficacy for gallbladder cancer
Chao Lv, Shukun Han, Baokang Wu, Zhiyun Liang, Yang Li, Yizhou Zhang, Qi Lang, Chongli Zhong, Lei Fu, Yang Yu, Feng Xu, Yu Tian
Frontiers in Immunology.2022;[Epub] CrossRef
PD-1 inhibitors plus nab-paclitaxel-containing chemotherapy for advanced gallbladder cancer in a second-line setting: A retrospective analysis of a case series
Sirui Tan, Jing Yu, Qiyue Huang, Nan Zhou, Hongfeng Gou
Frontiers in Oncology.2022;[Epub] CrossRef
Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma
You-Na Sung, Sung Joo Kim, Sun-Young Jun, Changhoon Yoo, Kyu-Pyo Kim, Jae Hoon Lee, Dae Wook Hwang, Shin Hwang, Sang Soo Lee, Seung-Mo Hong
Frontiers in Oncology.2021;[Epub] CrossRef
Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
Thomas Albrecht, Fritz Brinkmann, Michael Albrecht, Anke S. Lonsdorf, Arianeb Mehrabi, Katrin Hoffmann, Yakup Kulu, Alphonse Charbel, Monika N. Vogel, Christian Rupp, Bruno Köhler, Christoph Springfeld, Peter Schirmacher, Stephanie Roessler, Benjamin Goep
Cancers.2021; 13(7): 1682. CrossRef
Immune Microenvironment in Gallbladder Adenocarcinomas
Pallavi A. Patil, Kara Lombardo, Weibiao Cao
Applied Immunohistochemistry & Molecular Morphology.2021; 29(8): 557. CrossRef
Molecular Targets and Emerging Therapies for Advanced Gallbladder Cancer
Matteo Canale, Manlio Monti, Ilario Giovanni Rapposelli, Paola Ulivi, Francesco Giulio Sullo, Giulia Bartolini, Elisa Tiberi, Giovanni Luca Frassineti
Cancers.2021; 13(22): 5671. CrossRef
Overview of current targeted therapy in gallbladder cancer
Xiaoling Song, Yunping Hu, Yongsheng Li, Rong Shao, Fatao Liu, Yingbin Liu
Signal Transduction and Targeted Therapy.2020;[Epub] CrossRef

Case Study

Combined Adenosquamous and Large Cell Neuroendocrine Carcinoma of the Gallbladder: Jiyoon Jung, Yang-Seok Chae, Chul Hwan Kim, Youngseok Lee, Jeong Hyeon Lee, Dong-Sik Kim, Young-Dong Yu, Joo Young Kim; J Pathol Transl Med. 2018;52(2):121-125. Published online October 5, 2017; DOI: https://doi.org/10.4132/jptm.2017.08.20

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Abstract PDF

Large cell neuroendocrine carcinoma (LCNEC) of the gallbladder is extremely rare and usually combined with other type of malignancy, mostly adenocarcinoma. We report an unusual case of combined adenosquamous carcinoma and LCNEC of the gallbladder in a 54-year-old woman. A radical cholecystectomy specimen revealed a 4.3×4.0 cm polypoid mass in the fundus with infiltration of adjacent liver parenchyma. Microscopically, the tumor consisted of two distinct components. Adenosquamous carcinoma was predominant and abrupt transition from adenocarcinoma to squamous cell carcinoma was observed. LCNEC showed round cells with large, vesicular nuclei, abundant mitotic figures, and occasional pseudorosette formation. The patient received adjuvant chemotherapy. However, multiple liver metastases were identified at 3-month follow-up. Metastatic nodules were composed of LCNEC and squamous cell carcinoma components. Detecting LCNEC component is important in gallbladder cancer, because the tumor may require a different chemotherapy regimen and show early metastasis and poor prognosis.

Citations

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Comparison of Metastatic Patterns Among Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Nonneuroendocrine Carcinomas of Various Primary Organs
Hyung Kyu Park, Ghee Young Kwon
Journal of Korean Medical Science.2023;[Epub] CrossRef
Clinical features and outcomes analysis of Gallbladder neuroendocrine carcinoma
Man Jiang, Yijing Zhang
Journal of Cancer Research and Therapeutics.2023; 19(4): 910. CrossRef
Primary mixed large cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder: A case report and literature review
Tingting Yu, Shike Li, Zhuo Zhang
Asian Journal of Surgery.2022; 45(11): 2336. CrossRef
Mixed neuroendocrine-non-neuroendocrine neoplasm of the gallbladder: case report and literature review
Xu Ren, Hong Jiang, Kan Sun, Xufu Qin, Yongping Qu, Tian Xia, Yan Chen
Diagnostic Pathology.2022;[Epub] CrossRef
Neuroendocrine Neoplasms of the Gallbladder: A Clinicopathological Analysis of 13 Patients and a Review of the Literature
Pengyan Wang, Jingci Chen, Ying Jiang, Congwei Jia, Junyi Pang, Shan Wang, Xiaoyan Chang, Oronzo Brunetti
Gastroenterology Research and Practice.2021; 2021: 1. CrossRef
Gallbladder Mixed Neuroendocrine-Non-neuroendocrine Neoplasm (MiNEN) Arising in Intracholecystic Papillary Neoplasm: Clinicopathologic and Molecular Analysis of a Case and Review of the Literature
Amedeo Sciarra, Edoardo Missiaglia, Mounir Trimech, Emmanuel Melloul, Jean-Philippe Brouland, Christine Sempoux, Stefano La Rosa
Endocrine Pathology.2020; 31(1): 84. CrossRef
Mixed neuroendocrine-non-neuroendocrine carcinoma of gallbladder: case report
Adam Skalický, Lucie Vištejnová, Magdaléna Dubová, Tomáš Malkus, Tomáš Skalický, Ondřej Troup
World Journal of Surgical Oncology.2019;[Epub] CrossRef

Original Articles

A Different Perspective on Macroscopic Sampling of Cholecystectomy Specimens: Asuman Argon, Ayşe Yağcı, Funda Taşlı, Tulu Kebat, Senem Deniz, Nazif Erkan, Gül Kitapçıoğlu, Enver Vardar; Korean J Pathol. 2013;47(6):519-525. Published online December 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.6.519

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Abstract PDF

Background

Because there may be interdepartmental differences in macroscopic sampling of cholecystectomy specimens, we aimed to investigate differences between the longitudinal sampling technique and our classical sampling technique in cholecystectomy specimens in which there was no obvious malignancy.

Methods

Six hundred eight cholecystectomy specimens that were collected between 2011 and 2012 were included in this study. The first group included 273 specimens for which one sample was taken from each of the fundus, body, and neck regions (our classical technique). The second group included 335 specimens for which samples taken from the neck region and lengthwise from the fundus toward the neck were placed together in one cassette (longitudinal sampling). The Pearson chi-square, Fisher exact, and ANOVA tests were used and differences were considered significant at p<.05.

Results

In the statistical analysis, although gallbladders in the first group were bigger, the average length of the samples taken in the second group was greater. Inflammatory cells, pyloric metaplasia, intestinal metaplasia, low grade dysplasia, and invasive carcinoma were seen more often in the second group.

Conclusions

In our study, the use of a longitudinal sampling technique enabled us to examine a longer mucosa and to detect more mucosal lesions than did our classical technique. Thus, longitudinal sampling can be an effective technique in detecting preinvasive lesions.

Citations

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Ultrasonographic features of gallbladder wall thickening in dogs with hypoalbuminemia
Masahiro Murakami, Hock Gan Heng, Sarah Steinbach, Mario Sola
Veterinary Quarterly.2023; 43(1): 1. CrossRef
Can the sampling method affect the detection of incidental gallbladder carcinoma? Comparative analysis of two sampling methods
Ezgi Hacihasanoglu, Esra Pasaoglu, Merve Cin, Enver Yarikkaya, Nevra Dursun, Sevim Baykal Koca
Annals of Diagnostic Pathology.2023; 67: 152187. CrossRef
Current management of incidental gallbladder cancer: A review
Claudio F. Feo, Giorgio C. Ginesu, Alessandro Fancellu, Teresa Perra, Chiara Ninniri, Giulia Deiana, Antonio M. Scanu, Alberto Porcu
International Journal of Surgery.2022; 98: 106234. CrossRef
Accuracy of Right Upper Quadrant Ultrasound in Estimating Gallbladder Wall Thickness
Lindsay Cefalu, Robert McMurray, Grant Sizemore, Gerald Bieniek, Michael Lustik, Christopher Yheulon
Surgical Laparoscopy, Endoscopy & Percutaneous Techniques.2019; 29(1): 26. CrossRef
Optimal block sampling of routine, non‐tumorous gallbladders
Newton A C S Wong
Histopathology.2017; 71(1): 162. CrossRef
The Relationship Between Intracholecystic Papillary-Tubular Neoplasms and Invasive Carcinoma of the Gallbladder
Asuman Argon, Funda Yılmaz Barbet, Deniz Nart
International Journal of Surgical Pathology.2016; 24(6): 504. CrossRef

Expression of MUC1 and MUC4 in Gallbladder Adenocarcinoma: Su-Mi Kim, Sun-Ju Oh, Bang Hur; Korean J Pathol. 2012;46(5):429-435. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.429

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Abstract PDF

Background

Recent reports have indicated that overexpression of mucin (MUC) 1 and/or MUC4 correlates with the occurrence and progression of extra-hepatobiliary malignancy. In this study, we investigated the expression of MUC1 and MUC4 and their prognostic significance in gallbladder adenocarcinoma.

Methods

We examined 54 surgical gallbladder adenocarcinoma samples by immunohistochemistry for MUC1 and MUC4 expression. Staining was evaluated as a sum score of extent and intensity, dividing the samples into low and high expression groups.

Results

The low expression group for both MUC1 and MUC4 was 10 samples (18.5%), and the high expression group was 44 samples (81.5%). High MUC1 expression was significantly correlated with more differentiated tumors (p=0.033), whereas high expression of MUC4 correlated with negative nodal status (p=0.012). Other pathological features were not correlated with MUC expression. Multivariate cox regression analysis showed that neither MUC1 nor MUC4 expression correlated with survival.

Conclusions

Although there were some correlations found, a prognostic role for either MUC1 or MUC4 expression in gallbladder carcinoma was not identified in this study. Further investigation is required.

Citations

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Expression of Mucoproteins in Gallbladder Cancer
Puneet Kumar, Priyesh Shukla, Soni Kumari, Ruhi Dixit, Gopeshwar Narayan, V. K. Dixit, A. K. Khanna
Indian Journal of Surgery.2022; 84(3): 456. CrossRef
Prognostic and clinicopathological value of MUC1 expression in colorectal cancer
Chao Li, Tao Liu, Libin Yin, Didi Zuo, Yuyang Lin, Lei Wang
Medicine.2019; 98(9): e14659. CrossRef
Prognostic Significance of Mucin Antigen MUC1 in Various Human Epithelial Cancers
Feng Xu, Fuquan Liu, Hongwei Zhao, Guangyu An, Guosheng Feng
Medicine.2015; 94(50): e2286. CrossRef
Increased Expression of CCN2, Epithelial Membrane Antigen, and Fibroblast Activation Protein in Hepatocellular Carcinoma with Fibrous Stroma Showing Aggressive Behavior
Gi Jeong Kim, Hyungjin Rhee, Jeong Eun Yoo, Jung Eun Ko, Jee San Lee, Hyunki Kim, Jin Sub Choi, Young Nyun Park, Philip C. Trackman
PLoS ONE.2014; 9(8): e105094. CrossRef
State-of-the-art in the management of locally advanced and metastatic gallbladder cancer
Mairéad G. McNamara, Cristiane Metran-Nascente, Jennifer J. Knox
Current Opinion in Oncology.2013; 25(4): 425. CrossRef
Clinicopathological and Prognostic Significance of MUC-2, MUC-4 and MUC-5AC Expression in Japanese Gastric Carcinomas
Li-Jun Xiao, Shuang Zhao, En-Hong Zhao, Xin Zheng, Wen-Feng Gou, Ya-Nan Xing, Yasuo Takano, Hua-Chuan Zheng
Asian Pacific Journal of Cancer Prevention.2012; 13(12): 6447. CrossRef

Case Reports

Mixed Endocrine-Exocrine Carcinoma of Gallbladder Derived from Dysplasia.: Min Jin Lhee, Ji Young Woo; Korean J Pathol. 2011;45(5):537-541.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.537

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Abstract PDF: A rare case of multiple mixed endocrine-exocrine carcinoma (MEEC) of gallbladder in a 68-year-old man is described. The lesions were two separate nodules (17x13x7 mm and 17 mm in length) on the mucosa, which were composed of predominant neuroendocrine carcinoma (NEC) infiltrating into the adventitia and minor portion of adenocarcinoma (AC) or high grade dysplasia (HGD) on the surface. Surrounding mucosa showed areas of low grade dysplasia (LGD). Two nodal metastases out of 16 nodes were found containing NEC component. By immunohistochemistry, human mutL homolog 1 (hMLH1), p53, human mutS homolog 2 (hMSH2) and human mutS homolog 6 (hMSH6) showed diffuse strong positive reaction in HGD, AC and NEC, contrasting with weak positive reaction in LGD. On genetic analysis, all lesions of HGD, AC, and NEC except for LGD showed positive loss of heterozygosity in D5S346 locus. For microsatellite instability and K-ras mutation tests, all lesions showed negative results. Common immunophenotypes and molecular results among HGD, AC, and NEC suggested that NEC of this MEEC was derived from the dysplasia-AC sequence.

Sarcomatoid Carcinoma of the Gallbladder with Pure Squamous Cell Carcinoma: A Brief Case Report.: Seungkoo Lee, Song Yi Kim, Seong Kweon Hong; Korean J Pathol. 2011;45(2):209-211.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.2.209

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Abstract PDF

We report here on a rare case of sarcomatoid carcinoma that contained an epithelial component of squamous cell carcinoma. A 77-year-old woman was found to have a gallbladder mass. The gallbladder showed a diffuse infiltrative wall mass with a polypoid lesion, and the mass measured 8x7x3 cm. There were no gallstones. Histologically, the tumor was composed of two components of squamous cell carcinoma and spindle cell malignancy. The tumor extended to the perimuscular connective tissue and one regional lymph node. The postoperative course was uneventful and the patient was well without tumor recurrence at one and a half months after surgery.

Citations

Citations to this article as recorded by

Carcinosarcoma of gallbladder: A world review
Thomas Zheng Jie Teng, Branden Qi Yu Chua, Vishal G Shelat
World Journal of Clinical Oncology.2021; 12(12): 1244. CrossRef

Original Articles

Expression of Cyclooxygenase-2 and Embryonic Lethal Abnormal Vision-Like Protein HuR in Gallbladder Carcinoma.: Sung Im Do, Gou Young Kim, Sung Jig Lim, Youn Wha Kim; Korean J Pathol. 2010;44(1):42-47.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.42

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Abstract PDF

BACKGROUND
Cyclooxygenase-2 (COX-2) is an enzyme that promotes proliferation of tumor cells. HuR is a member of the family of embryonic lethal abnormal vision-like proteins. Recent studies show that cytoplasmic HuR stabilizes the mRNA of COX-2 and regulates the expression of COX-2. Moreover, cytoplasmic HuR expression is associated with a poorer prognosis for patients with some cancers. The aim of this study was to investigate the expression patterns of and the relationship between COX-2 and HuR in gallbladder carcinoma.
METHODS
We analyzed COX-2 and HuR expression by immunohistochemical staining of 108 gallbladder carcinomas.
RESULTS
COX-2 expression and nuclear and cytoplasmic HuR expression were seen in, respectively, 61 (56.5%), 77 (71.3%), and 4 (3.7%) cases. COX-2 and nuclear HuR were simultaneously expressed in 44 of the 108 samples without any quantitative association between the levels of each. COX-2 expression correlated with tumor stage, differentiation (based on histology), lymph node metastasis, perineural invasion, and survival. Nuclear and cytological expression of HuR did not correlate with any clinical parameters.
CONCLUSIONS
COX-2 expression but not HuR may play an important role in the prognosis of patients with gallbladder carcinoma.

Citations

Citations to this article as recorded by

Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers
Robert P Jones, Nicholas TE Bird, Richard A Smith, Daniel H Palmer, Steven W Fenwick, Graeme J Poston, Hassan Z Malik
Biomarkers in Medicine.2015; 9(8): 763. CrossRef

Alpha-Fetoprotein-Producing Carcinoma of the Gallbladder.: Young Ha Oh, Haeng Ji Kang, Hyoung Guen Lee, Eun Kyung Hong, Yong Il Kim, Jung Dal Lee; Korean J Pathol. 1996;30(5):453-456.

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Abstract PDF: Alpha-fetoprotein (AFP) is a well-known tumor marker for hepatocellular carcinoma, hepatoblastoma, and yolk sac tumors. There are several studies on AFP-producing tumors that arose from the gastrointestinal tract, pancreas, lung, kidney, and urachal tract. AFP-producing carcinoma of the gallbladder is extremely rare. We report a case of AFP-producing carcinoma of the gallbladder without liver involvement in a 58-year-old man with a gallstone, on which clinical, morphologic, and immunohistochemical studies were performed.

Hyperplasia, Metaplasia, and Dysplasia of the Gallbladder Correlation to Gallbladder Adenocarcinoma.: Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(6):527-537.

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Abstract PDF: The correlation of metaplasia to dysplasia and carcinoma in the gallbladder has attracted the attention of many investigators. We mapped and examined a total of 263 cholecystectomized gallbladders to analyze the mucosal changes in the carcinogenesis of the gallbladder. Stones were present in 59.7%, hyperplasia in 28.5%, metaplasia in 55.5% (gastric 37.6%, intestinal 17.9%), dysplasia in 17.1% (low grade 9.1%, high grade 8%) and carcinoma in 7.6%. Metaplasia was more frequently identified in the stone-positive group (62.4%) than in the stone-negative group (45.3%) (P<0.05). Especially, the incidence of intestinal metaplasia was significantly higher in the stone-positive group. Dysplasia and carcinoma were more frequent in the metaplasia-positive group (dysplasia 26.7%, carcinoma 11%) than in the metaplasia-negative group (dysplasia 5.1%, carcinoma 3.4%) (P<0.05). Their incidences were significantly higher in the intestinal metaplasia than in the gastric metaplasia. Forty four percent of the dysplasia-positive cases were associated with carcinoma in the adjacent mucosa but carcinoma was absent in the dysplasia-negative cases. Hyperplasia did not reveal any significant correlation with metaplasia, dysplasia and carcinoma. These results suggest that gallstone is causally related to the metaplasia in the gallbladder and the metaplasia-dysplasia- carcinoma sequence exists in the gallbladder.

Pathologic Analysis of Gallbladder Cancer by the Stage and Intestinal Metaplasia with the Diagnostic Significance of CEA and p53.: Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(7):599-607.

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Abstract PDF: Twenty cases of gallbladder cancers were examined using 5 mm stepwise tissue sections. We analyzed the clinicopathologic findings of the early (stage 1, II) and advanced carcinoma (stage III, IV, V) and those of carcinoma with or without metaplasia in the tumor. We also performed CEA and p53 immunohistochemical staining and compared their findings with those of normal mucosa and preneoplastic lesions. The results were as follow: 1) All of the early carcinomas (n=5) were incidentally diagnosed after the resection for the gallstone. They were compared to advanced carcinoma (n=15) in the absence of the lymphatic or angioinvasion, recurrence, metastasis and death. 2) Metaplastic and non-metaplastic carcinoma did not reveal any difference of the clinicopathologic findings except age distribution. 3) CEA and p53 were positive in preneoplastic and malignant lesions. The extent of staining was related to the degree of the atypia. From the above results, an early detection of gallbladder cancer is very important for the prognosis of the patients. Since preoperative diagnosis is difficult, thorough pathologic examination of routinely resected gallbladder is necessary for the early diagnosis. CEA and p53 immunohistochemical staining may be helpful in the differential diagnosis of non-neoplastic and neoplastic lesion of the gallbladder.

Case Report

Necrotizing Vasculitis of the Gallbladder: A case report.: Ah Won Lee, Youn Soo Lee, Seok Jin Kang, Byung Kee Kim, Sang In Shim; Korean J Pathol. 1999;33(4):292-294.

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Abstract PDF: We report a case of necrotizing arteritis involving the gallbladder. This case was clinically diagnosed as cholelithiasis with cholecystitis, and necrotizing arteritis was found in the surgically resected specimen. Vascular changes were similar to those seen in classic polyarteritis nodosa, involving medium-sized muscular arteries and characterized by fibrinoid necrosis and panarterial and periarterial inflammation varying from active to resolving stages. Acute cholecystitis is a rare initial clinical manifestation of the systemic vasculitis. If acute cholecystitis is found in the absence of obvious cause, careful examination is essential. Since steroid therapy improves the prognosis in the systemic vasculitis, clinicians and pathologists should be aware of this unusual lesion.

Original Article

Expression of Matrix Metalloproteinase (MMP)-2, MMP-9, Tissue Inhibitor of Metalloproteinase (TIMP)-1 and TIMP-2 in Adenocarcinomas of The Gallbladder.: Jong Yup Bae, Jinsub Choi, Hyun Cheol Chung, Chanil Park, Young Nyun Park; Korean J Pathol. 2003;37(1):1-9.

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Abstract PDF: BACKGROUND
Matrix metalloproteinase (MMP)-2 and MMP-9 degrade type IV collagen and are antagonized by the tissue inhibitors of metalloproteinase (TIMP)-2 and TIMP-1, respectively.
METHODS
We studied by immunohistochemistry the expressions of MMP-2, MMP-9, TIMP-1 and TIMP-2 in 72 cases of adenocarcinoma of the gallbladder.
RESULTS
The MMP-2, MMP-9 and TIMP-1 expressions were significantly higher in well/moderately differentiated adenocarcinomas than in poorly differentiated adenocarcinomas, in adenocarcinomas that had invaded the lamina propria/proper muscle than in those that had invaded the perimuscular connective tissue or beyond the serosa, and in adenocarcinomas with fungating growth than in those with infiltrative growth. The TIMP-2 expression showed a similar pattern without statistical significance. Regarding the status of lymph node metastasis, the MMP-2 expression was significantly higher in cases without lymph node metastasis. The MMP-2 and MMP-9 expressions were significantly related to those of TIMP-2 and TIMP-1, respectively, with regard to depth of invasion, differentiation, and growth patterns of the adenocarcinomas.
CONCLUSIONS
MMP-2, MMP-9, TIMP-1 and TIMP-2 are suggested to play important roles in the progression to early invasion of adenocarcinomas, in which the function of MMP-2 is inhibited by TIMP-2.

Case Reports

Micropapillary Carcinoma of the Gallbladder.: Dae Woon Eom, Gil Hyun Kang, Hyuk Jai Gang; Korean J Pathol. 2008;42(3):162-164.

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Abstract PDF: Micropapillary carcinoma (MPC) is a rare variant of carcinoma, and it is composed of small papillary neoplastic cell clusters lying within clear lacunar spaces that simulate lymphovascular channels. This tumor has been described in the several organs such as the breast, lung, urinary bladder and salivary gland and it is known to be frequently associated with a high incidence of lymphatic invasion and metastasis in lymph nodes, resulting in poor clinical outcome. We present here a case of MPC in the gall bladder, and this type of case has not been previously described. Histologically, the tumor was composed of micropapillary carcinoma with tight clusters of micropapillary aggregates in the background of tubular adenoma. Focal invasive micropapillary components were also noted in the submuscular connective tissue. A metastatic lesion in a regional lymph node also showed an entirely micropapillary pattern.

Ectopic Liver Associated with the Gallbladder: A Brief Case Report.: Hee Eun Kyeong, Younghee Park, Sanghui Park; Korean J Pathol. 2008;42(2):128-130.

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Abstract PDF: Ectopic liver is a rare entity that has been previously identified during abdominal exploration for other surgery and this has usually been described in the vicinity of the liver such as on the gallbladder, hepatic ligaments, diaphragm, thoracic cavity, adrenal glands, pancreas, omentum, spleen, esophagus and umbilical cord. Most cases of ectopic liver reported in the literature were located in the gallbladder. We report here on a case of ectopic liver related to the gallbladder, and this was encountered during an elective laparoscopic cholecystectomy.

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