Journal of Pathology and Translational Medicine

Volume 53(2); March 2019

Original Articles

Loss of Human Leukocyte Antigen Class I Expression Is Associated with Poor Prognosis in Patients with Advanced Breast Cancer: Hong Sik Park, Uiju Cho, So Young Im, Chang Young Yoo, Ji Han Jung, Young Jin Suh, Hyun Joo Choi; J Pathol Transl Med. 2019;53(2):75-85. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.11

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Background
Human leukocyte antigen class I (HLA-I) molecules play important roles in regulating immune responses. Loss or reduction of HLA-I expression has been shown to be associated with prognosis in several cancers. Regulatory T-cells (Tregs) also play critical functions in immune response regulation. Evaluation of HLA-I expression status by the EMR8-5 antibody and its clinical impact in breast cancer have not been well studied, and its relationship with Tregs remains unclear.
Methods
We evaluated HLA-I expression and Treg infiltration by immunohistochemistry in 465 surgically resected breast cancer samples. We examined the correlation between HLA-I expression and Treg infiltration and clinicopathologic characteristics and survival analyses were performed.
Results
Total loss of HLA-I expression was found in 84 breast cancer samples (18.1%). Univariate survival analysis revealed that loss of HLA-I expression was significantly associated with worse disease-specific survival (DSS) (p = .029). HLA-I was not an independent prognostic factor in the entire patient group, but it was an adverse independent prognostic factor for DSS in patients with advanced disease (stage II–IV) (p = .031). Treg numbers were significantly higher in the intratumoral stroma of HLA-I–positive tumors than in HLA-I–negative tumors (median 6.3 cells/high power field vs 2.1 cells/high power field, p < .001). However, Tregs were not an independent prognostic factor in our cohort.
Conclusions
Our findings suggest that the loss of HLA-I expression is associated with poor prognosis in breast cancer patients, highlighting the role of HLA-I alterations in immune evasion mechanisms of breast cancer. HLA-I could be a promising marker that enables the application of more effective and precise immunotherapies for patients with advanced breast cancer.

Citations

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Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy
Chiara Corti, Busem Binboğa Kurt, Beyza Koca, Tasnim Rahman, Fabio Conforti, Laura Pala, Giampaolo Bianchini, Carmen Criscitiello, Giuseppe Curigliano, Ana C. Garrido-Castro, Sheheryar K. Kabraji, Adrienne G. Waks, Elizabeth A. Mittendorf, Sara M. Tolaney
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MHC-I upregulation by macbecin II in the solid tumors potentiates the effect of active immunotherapy
Ravindra Pramod Deshpande, Kerui Wu, Shih-Ying Wu, Abhishek Tyagi, Eleanor C Smith, Jee-Won Kim, Kounosuke Watabe
EMBO Molecular Medicine.2025;[Epub] CrossRef
Programmed Cell Death Ligand 1 (PD-L1) and major Histocompatibility Complex Class I (MHC Class I) Expression Patterns and Their Pathologic Associations in triple-Negative Breast Cancer
Ponkrit Kaewkedsri, Piyapharom Intarawichian, Sirawich Jessadapattarakul, Waritta Kunprom, Supinda Koonmee, Malinee Thanee, Ongart Somintara, Anongporn Wongbuddha, Payia Chadbunchachai, Supajit Nawapun, Chaiwat Aphivatanasiri
Breast Cancer: Targets and Therapy.2025; Volume 17: 123. CrossRef
Comment on “Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta‑Analysis”
Wei Han, Li-zhou Shi, Yu-wei Zhang, Hao-nan Wang
Molecular Diagnosis & Therapy.2024; 28(2): 237. CrossRef
Immunotherapy resistance in solid tumors: mechanisms and potential solutions
Daniel S. Lefler, Steven A. Manobianco, Babar Bashir
Cancer Biology & Therapy.2024;[Epub] CrossRef
Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe
HLA.2024;[Epub] CrossRef
Human Leukocyte Antigen Class I Expression and Natural Killer Cell Infiltration and Its Correlation with Prognostic Features in Luminal Breast Cancers
Maria Vernet-Tomas, Ivonne Vazquez, Francesc Olivares, David Lopez, Jose Yelamos, Laura Comerma
Breast Cancer: Targets and Therapy.2024; Volume 16: 657. CrossRef
Upregulation of MHC I antigen processing machinery gene expression in breast cancer cells by Trichostatin A
A. H. Murtadha, N. A. Sharudin, I. I.M. Azahar, A. T. Che Has, N. F. Mokhtar
Молекулярная биология.2024; 58(1): 121. CrossRef
HLA-I and breast cancer prognosis: A systematic review and meta-analysis
Francisco Cezar Aquino de Moraes, Jorge Henrique Cavalcanti Orestes Cardoso, Francinny Alves Kelly, Michele Kreuz, Lilianne Rodrigues Fernandes, Maria Cristina Figueroa Magalhães, Rommel Mario Rodríguez Burbano
Human Immunology.2024; 85(6): 111148. CrossRef
Cancer Immunology: Immune Escape of Tumors—Expression and Regulation of HLA Class I Molecules and Its Role in Immunotherapies
Yuan Wang, Simon Jasinski-Bergner, Claudia Wickenhauser, Barbara Seliger
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Diego Morazán-Fernández, Javier Mora, Jose Arturo Molina-Mora
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HLA and tumour immunology: immune escape, immunotherapy and immune-related adverse events
Ning Jiang, Yue Yu, Dawei Wu, Shuhang Wang, Yuan Fang, Huilei Miao, Peiwen Ma, Huiyao Huang, Min Zhang, Yu Zhang, Yu Tang, Ning Li
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Sonya Youngju Park, Deog-Gon Cho, Byoung-Yong Shim, Uiju Cho
Diagnostics.2023; 13(6): 1013. CrossRef
Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis
Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng
Molecular Diagnosis & Therapy.2023; 27(5): 573. CrossRef
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Manish Malviya, Zita E. H. Aretz, Zaki Molvi, Jayop Lee, Stephanie Pierre, Patrick Wallisch, Tao Dao, David A. Scheinberg
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Molecular mechanisms of impaired antigenic presentation as a cause of tumor escape from immune surveillance
A.A. Korotaeva, A.A. Borunova, A.Yu. Kuzevanova, T.N. Zabotina, A.A. Alimov
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Immune Escape Mechanism of Cancer
Ayse Caner
Current Molecular Biology Reports.2023; 10(1): 9. CrossRef
Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A
A. H. Murtadha, N. A. Sharudin, I. I. M. Azahar, A. T. Che Has, N. F. Mokhtar
Molecular Biology.2023; 57(6): 1212. CrossRef
Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors
Ananthan Sadagopan, Theodoros Michelakos, Gabriella Boyiadzis, Cristina Ferrone, Soldano Ferrone
JAMA Oncology.2022; 8(3): 462. CrossRef
Mechanisms of MHC-I Downregulation and Role in Immunotherapy Response
Brandie C. Taylor, Justin M. Balko
Frontiers in Immunology.2022;[Epub] CrossRef
Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives
Ioannis A. Vathiotis, Ioannis Trontzas, Niki Gavrielatou, Georgia Gomatou, Nikolaos K. Syrigos, Elias A. Kotteas
Clinical Breast Cancer.2022; 22(7): 642. CrossRef
Aberrant synaptophysin expression in classic Hodgkin lymphoma
Soyoung Im, Jeong-A. Kim, Gyeongsin Park, Uiju Cho
Diagnostic Pathology.2022;[Epub] CrossRef
Expression of HLA class I is associated with immune cell infiltration and patient outcome in breast cancer
Song-Hee Han, Milim Kim, Yul Ri Chung, Ji Won Woo, Hye Yeon Choi, So Yeon Park
Scientific Reports.2022;[Epub] CrossRef
Immune landscape and therapeutic strategies: new insights into PD-L1 in tumors
Yuan Wei, Xiao Xiao, Xiang-Ming Lao, Limin Zheng, Dong-Ming Kuang
Cellular and Molecular Life Sciences.2021; 78(3): 867. CrossRef
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer
Leisha A Emens, Sylvia Adams, Ashley Cimino-Mathews, Mary L Disis, Margaret E Gatti-Mays, Alice Y Ho, Kevin Kalinsky, Heather L McArthur, Elizabeth A Mittendorf, Rita Nanda, David B Page, Hope S Rugo, Krista M Rubin, Hatem Soliman, Patricia A Spears, Sara
Journal for ImmunoTherapy of Cancer.2021; 9(8): e002597. CrossRef
Resistance mechanisms to checkpoint inhibitors
Sarah A Weiss, Mario Sznol
Current Opinion in Immunology.2021; 69: 47. CrossRef
The Immunology of Hormone Receptor Positive Breast Cancer
Jonathan Goldberg, Ricardo G. Pastorello, Tuulia Vallius, Janae Davis, Yvonne Xiaoyong Cui, Judith Agudo, Adrienne G. Waks, Tanya Keenan, Sandra S. McAllister, Sara M. Tolaney, Elizabeth A. Mittendorf, Jennifer L. Guerriero
Frontiers in Immunology.2021;[Epub] CrossRef
B4GALNT2 Gene Promotes Proliferation, and Invasiveness and Migration Abilities of Model Triple Negative Breast Cancer (TNBC) Cells by Interacting With HLA-B Protein
Pu Yu, Lili Zhu, Kang Cui, Yabing Du, Chaojie Zhang, Wang Ma, Jia Guo
Frontiers in Oncology.2021;[Epub] CrossRef
Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies
Nina Radosevic-Robin, Pier Selenica, Yingjie Zhu, Helen H. Won, Michael F. Berger, Lorenzo Ferrando, Emiliano Cocco, Maud Privat, Flora Ponelle-Chachuat, Catherine Abrial, Jean-Marc Nabholtz, Frederique Penault-Llorca, Jorge S. Reis-Filho, Maurizio Scaltr
npj Breast Cancer.2021;[Epub] CrossRef
Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?
Liam Masterson, James Howard, Jazmina Gonzalez‐Cruz, Christopher Jackson, Catherine Barnett, Lewis Overton, Howard Liu, Rahul Ladwa, Fiona Simpson, Margie McGrath, Ben Wallwork, Terry Jones, Christian Ottensmeier, Melvin L.K. Chua, Chris Perry, Rajiv Khan
International Journal of Cancer.2020; 146(8): 2305. CrossRef
Co-expression of HLA-I loci improved prognostication in HER2+ breast cancers
Julia Y. Tsang, Chun-Sing Ho, Yun-Bi Ni, Yan Shao, Ivan K. Poon, Siu-Ki Chan, Sai-Yin Cheung, Ka-Ho Shea, Monalyn Marabi, Gary M. Tse
Cancer Immunology, Immunotherapy.2020; 69(5): 799. CrossRef
Breast cancer patients overall survival depends on a combination of the polymorphisms of tumor necrosis factor gene and HLA-haplotypes
T.F. Malivanova, E.V. Alferova, A.S. Ostashkin, T.A. Astrelina, N.N. Mazurenko
Molecular Genetics Microbiology and Virology (Russian version).2020; 38(1): 40. CrossRef
The Overall Survival of Breast Cancer Patients Depends on a Combination of Polymorphisms of Tumor Necrosis Factor Gene and HLA Haplotypes
T. F. Malivanova, E. V. Alferova, A. S. Ostashkin, T. A. Astrelina, N. N. Mazurenko
Molecular Genetics, Microbiology and Virology.2020; 35(1): 38. CrossRef
The Emergence of Natural Killer Cells as a Major Target in Cancer Immunotherapy
Fernando Souza-Fonseca-Guimaraes, Joseph Cursons, Nicholas D. Huntington
Trends in Immunology.2019; 40(2): 142. CrossRef

Human Leukocyte Antigen Class I and Programmed Death-Ligand 1 Coexpression Is an Independent Poor Prognostic Factor in Adenocarcinoma of the Lung: Yeon Bi Han, Hyun Jung Kwon, Soo Young Park, Eun-Sun Kim, Hyojin Kim, Jin-Haeng Chung; J Pathol Transl Med. 2019;53(2):86-93. Published online January 14, 2019; DOI: https://doi.org/10.4132/jptm.2018.12.26

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Abstract PDF

Background
Both human leukocyte antigen (HLA) class I and programmed death-ligand 1 (PD-L1) molecules are known to play important roles in cancer immunity. In this study, we evaluated HLA class I expression in resected adenocarcinoma of the lung, and investigated its prognostic impact in correlation with PD-L1 expression.
Methods
HLA class I and PD-L1 expression was evaluated by immunohistochemistry in a total of 403 resected lung adenocarcinomas using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed.
Results
HLA class I expression was reduced in 91.6% of adenocarcinoma, and more frequently reduced in patients with younger age, absence of vascular invasion, and low pathologic stage (p = .033, p = .007, and p = .012, respectively). Positive PD-L1 expression in tumor cells was 16.1% (1% cut-off), and associated with poor differentiation, presence of vascular invasion and nodal metastasis (p < .001, p = .002, and p = .032, respectively). On survival analysis, HLA class I or PD-L1 expression alone did not show any statistical significance. On the integrated analysis, HLA class I (+)/PD-L1 (+) subgroup showed a significantly shorter overall survival than other groups (p = .001). Multivariate analysis revealed that coexpression of HLA class I and PD-L1 was an independent poor prognostic factor of lung adenocarcinoma. (p < .001; hazard ratio, 6.106; 95% confidence interval, 2.260 to 16.501).
Conclusions
Lung adenocarcinoma with coexpression of HLA class I and PD-L1 was associated with poor prognosis. This subgroup may evade immune attack by expressing PD-L1 protein despite HLA expression.

Citations

Citations to this article as recorded by

Assessment of cancer cell‐expressed HLA class I molecules and their immunopathological implications
Terufumi Kubo, Shiori Asano, Kenta Sasaki, Kenji Murata, Takayuki Kanaseki, Tomohide Tsukahara, Yoshihiko Hirohashi, Toshihiko Torigoe
HLA.2024;[Epub] CrossRef
Prognostic and Clinical Significance of Human Leukocyte Antigen Class I Expression in Breast Cancer: A Meta-Analysis
Weiqiang Qiao, Zhiqiang Jia, Wanying Guo, Qipeng Liu, Xiao Guo, Miao Deng
Molecular Diagnosis & Therapy.2023; 27(5): 573. CrossRef
Loss of HLA-class-I expression in non-small-cell lung cancer: Association with prognosis and anaerobic metabolism
Ioannis M. Koukourakis, Alexandra Giatromanolaki, Achilleas Mitrakas, Michael I. Koukourakis
Cellular Immunology.2022; 373: 104495. CrossRef

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

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Abstract PDF Supplementary Material

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

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Frontiers in Pharmacology.2024;[Epub] CrossRef
ER stress signaling at the interphase between MASH and HCC
Younis Hazari, Eric Chevet, Béatrice Bailly-Maitre, Claudio Hetz
Hepatology.2024;[Epub] CrossRef
Small molecules for impairing endoplasmic reticulum in cancer
Tripti Mishra, Navneet Dubey, Sudipta Basu
Organic & Biomolecular Chemistry.2024; 22(44): 8689. CrossRef
Guanabenz acetate, an antihypertensive drug repurposed as an inhibitor of Escherichia coli biofilm
Arakkaveettil Kabeer Farha, Olivier Habimana, Harold Corke, Olaya Rendueles
Microbiology Spectrum.2024;[Epub] CrossRef
The integrated stress response in cancer progression: a force for plasticity and resistance
Caleb L. Lines, Morgan J. McGrath, Tanis Dorwart, Crystal S. Conn
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Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma
Jiacheng Wu, Shan Qiao, Yien Xiang, Menying Cui, Xiaoxiao Yao, Ruixin Lin, Xuewen Zhang
Biomedicine & Pharmacotherapy.2021; 142: 112005. CrossRef
The two faces of the Integrated Stress Response in cancer progression and therapeutic strategies
Eugenia Licari, Luis Sánchez-del-Campo, Paola Falletta
The International Journal of Biochemistry & Cell Biology.2021; 139: 106059. CrossRef
Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer
Yusuf A. Haggag, Mohamed Yasser, Murtaza M. Tambuwala, Suleiman S. El Tokhy, Mohammad Isreb, Ahmed A. Donia
International Journal of Pharmaceutics.2021; 600: 120532. CrossRef
Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases
Marina S. Gorbatyuk, Christopher R. Starr, Oleg S. Gorbatyuk
Progress in Retinal and Eye Research.2020; 79: 100860. CrossRef
Delineating the role of eIF2α in retinal degeneration
Christopher R. Starr, Marina S. Gorbatyuk
Cell Death & Disease.2019;[Epub] CrossRef
Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
Areeba Anwar, Mohammad Ridwane Mungroo, Ayaz Anwar, William J. Sullivan, Naveed Ahmed Khan, Ruqaiyyah Siddiqui
ACS Infectious Diseases.2019; 5(12): 2039. CrossRef

Intraoperative Frozen Cytology of Central Nervous System Neoplasms: An Ancillary Tool for Frozen Diagnosis: Myunghee Kang, Dong Hae Chung, Na Rae Kim, Hyun Yee Cho, Seung Yeon Ha, Sangho Lee, Jungsuk An, Jae Yeon Seok, Gie-Taek Yie, Chan Jong Yoo, Sang Gu Lee, Eun Young Kim, Woo Kyung Kim, Seong Son, Sun Jin Sym, Dong Bok Shin, Hee Young Hwang, Eung Yeop Kim, Kyu Chan Lee; J Pathol Transl Med. 2019;53(2):104-111. Published online January 14, 2019; DOI: https://doi.org/10.4132/jptm.2018.11.10

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Abstract PDF

Background
Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms.
Methods
Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated.
Results
Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency.
Conclusions
Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

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Takahiro Hayashi, Kensuke Tateishi, Shinichiro Matsuyama, Hiromichi Iwashita, Yohei Miyake, Akito Oshima, Hirokuni Honma, Jo Sasame, Katsuhiro Takabayashi, Kyoka Sugino, Emi Hirata, Naoko Udaka, Yuko Matsushita, Ikuma Kato, Hiroaki Hayashi, Taishi Nakamur
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Xinke Zhang, Zihan Zhao, Ruixuan Wang, Haohua Chen, Xueyi Zheng, Lili Liu, Lilong Lan, Peng Li, Shuyang Wu, Qinghua Cao, Rongzhen Luo, Wanming Hu, Shanshan lyu, Zhengyu Zhang, Dan Xie, Yaping Ye, Yu Wang, Muyan Cai
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Muhammad Shakir, Ahmed Altaf, Hawra Hussain, Syed Muhammad Aqeel Abidi, Zoey Petitt, Mahnoor Tariq, Ahmed Gilani, S. Ather Enam
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B N Kumarguru, G Santhipriya, S Kranthi Kumar, R Ramesh Kumar, A S Ramaswamy, P Janakiraman
Journal of Cytology.2022; 39(1): 1. CrossRef
Intraoperative squash cytology provides a qualitative intraoperative diagnosis for cases in which frozen section yields a diagnosis of equivocal brain tumour
Hirotaka Fujita, Takuma Tajiri, Tomohisa Machida, Nozomi Nomura, Suguru Toguchi, Hitoshi Itoh, Shinichiro Hiraiwa, Tomoko Sugiyama, Masaaki Imai, Shinri Oda, Masami Shimoda, Naoya Nakamura
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Na Rae Kim, Gie-Taek Yie
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Case Studies

Squamous Cell Carcinoma of the Extrahepatic Common Hepatic Duct: Myunghee Kang, Na Rae Kim, Dong Hae Chung, Hyun Yee Cho, Yeon Ho Park; J Pathol Transl Med. 2019;53(2):112-118. Published online October 1, 2018; DOI: https://doi.org/10.4132/jptm.2018.09.03

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Abstract PDF

We report a rare case of hilar squamous cell carcinoma. A 62-year-old Korean woman complaining of nausea was referred to our hospital. Her biliary computed tomography revealed a 28 mm-sized protruding solid mass in the proximal common bile duct. The patient underwent left hemihepatectomy with S1 segmentectomy and segmental excision of the common bile duct. Microscopically, the tumor was a moderately differentiated squamous cell carcinoma of the extrahepatic bile duct, without any component of adenocarcinoma or metaplastic portion in the biliary epithelium. Immunohistochemically, the tumor was positive for cytokeratin (CK) 5/6, CK19, p40, and p63. Squamous cell carcinoma of the extrahepatic bile duct is rare. To date, only 24 cases of biliary squamous cell carcinomas have been reported. Here, we provide a clinicopathologic review of previously reported extrahepatic bile duct squamous cell carcinomas.

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Heparin

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Gastroenterología y Hepatología.2019; 42(7): 436. CrossRef
Primary squamous cell carcinoma of the extrahepatic bile duct: A case report
Ana Delgado Maroto, Andrés Barrientos Delgado, Marta Lázaro Sáez, Samia Hallouch Toutouh, Enrique Práxedes González
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Primary Malignant Melanoma of the Breast: A Report of Two Cases: Jiwon Koh, Jihyeon Lee, So Youn Jung, Han Sung Kang, Tak Yun, Youngmee Kwon; J Pathol Transl Med. 2019;53(2):119-124. Published online November 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.18

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Abstract PDF Supplementary Material

Primary malignant melanoma of the breast (PMMB) is a rare tumor with only a few case reports available in the literature. We report two cases of PMMB, one derived from the breast parenchyma and the other from the breast skin. The first case consisted of atypical epithelioid cells without overt melanocytic differentiation like melanin pigments. The tumor cells showed diffuse positivity for S100 protein, tyrosinase, and BRAF V600E. However, the tumor cells were negative for cytokeratin, epithelial membrane antigen, and HMB-45. The second case showed atypical melanocytic proliferation with heavy melanin pigmentation. The tumor cells were positive for S100 protein, HMB-45, tyrosinase, and BRAF V600E. These two cases represent two distinct presentations of PMMB in terms of skin involvement, melanin pigmentation, and HMB-45 positivity. Although PMMB is very rare, the possibility of this entity should be considered in malignant epithelioid neoplasms in the breast parenchyma.

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Coexisting Mucinous Cystic Neoplasm of the Pancreas and Type 1 Autoimmune Pancreatitis: Mee-Jeong Kim, Tae Jun Song, Hyoung Jung Kim, Song-Cheol Kim, Myung-Hwan Kim, Seung-Mo Hong; J Pathol Transl Med. 2019;53(2):125-128. Published online November 14, 2018; DOI: https://doi.org/10.4132/jptm.2018.10.25

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Abstract PDF

Type 1 autoimmune pancreatitis (AIP1) is an IgG4-related systemic disease that mimics tumors. We report a rare case of AIP1 accompanied by mucinous cystic neoplasm (MCN). A pancreatic lesion was incidentally detected in a woman in her 60s. After 6 years of follow-up, the lesion abruptly increased in size. Computed tomography showed a 3.5 cm unilocular cyst in the tail of the pancreas and distal pancreatectomy was performed. On microscopic examination, the cyst was lined by mucinous and non-mucinous epithelial cells with mild cytologic atypia. The surrounding stroma comprised ovarian-type spindle cells with progesterone receptor positivity. The pericystic pancreas exhibited multifocal lymphoid follicles, lymphoplasmacytic infiltrations, obliterative phlebitis, and storiform fibrosis. IgG4-positive plasma cell infiltration (215 cells high-power field) and the IgG4/IgG ratio (57%) were increased. Cases of MCN coexisting with AIP1 are extremely rare; only two such cases have been reported in the English-language literature. This third case featured low-grade MCN with AIP1.

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Patients with Beckwith-Wiedemann syndrome (BWS) are predisposed to developing embryonal tumors, with hepatoblastoma being the most common type. Our patient showed hemihypertrophy, macroglossia, and paternal uniparental disomy in chromosome 11 and was diagnosed with BWS. When the patient was 9 months old, a 2.5×1.5 cm oval hypoechoic exophytic mass was detected in the inferior tip of his right liver. Preoperative imaging identified it as hepatoblastoma; however, histologic, immunohistochemistry, and electron microscopic findings were compatible with adrenal cortical neoplasm with uncertain malignant potential. The origin of the adrenal tissue seemed to be heterotopic. Here, we describe for the first time an adrenal cortical neoplasm with uncertain malignant potential arising in the heterotopic adrenal cortex located in the liver of a patient with BWS.

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Although papillary thyroid carcinoma (PTC)–type nuclear changes are the most reliable morphological feature in the diagnosis of PTC, the nuclear assessment used to identify these changes is highly subjective. Here, we report a noninvasive encapsulated thyroid tumor with a papillary growth pattern measuring 23 mm at its largest diameter with a nuclear score of 2 in a 26-year-old man. After undergoing left lobectomy, the patient was diagnosed with an encapsulated PTC. However, a second opinion consultation suggested an alternative diagnosis of follicular adenoma with papillary hyperplasia. When providing a third opinion, we identified a low MIB-1 labeling index and a heterozygous point mutation in the KRAS gene but not the BRAF gene. We speculated that this case is an example of a novel borderline tumor with a papillary structure. Introduction of the new terminology “noninvasive encapsulated papillary RAS-like thyroid tumor (NEPRAS)” without the word “cancer” might relieve the psychological burden of patients in a way similar to the phrase “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).”

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