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1
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Gauger AJ, Li A, Fritz M, Katona TM, Alomari AK. Use of Albumin In Situ Hybridization to Diagnose Cutaneous Metastatic Hepatocellular Carcinoma With Poorly Differentiated Features: A Case Report and Review of the Literature. Am J Dermatopathol 2025; 47:211-216. [PMID: 39481028 DOI: 10.1097/dad.0000000000002854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2024]
Abstract
ABSTRACT Hepatocellular carcinoma (HCC) rarely metastasizes to the skin. When it occurs, it is often poorly differentiated making the diagnosis challenging. There exists a male predominance, and clinical presentation usually includes papules or nodules resembling pyogenic granulomas or dermal deposits. Histopathology shows malignant dermal cells. Hepatoid features including nests or cords of cells arranged in a trabecular or pseudoglandular pattern, sinusoidal formation, or the presence of bile exist in less than 50% of cases. Limitations exist with immunohistochemical staining, particularly in poorly differentiated neoplasms. Albumin in situ hybridization is more sensitive for detecting poorly differentiated HCC. Immunostaining in conjugation with albumin in situ hybridization enhances the detection of metastatic hepatocellular carcinoma. We report the case of a 74-year-old man with a history of HCC and a stable lung metastasis who presented with painful, growing bumps on his nose for 2 months. Examination revealed multiple, pink to white, shiny dermal-based papules with telangiectasias involving the right nasal tip and naris. Alpha-fetoprotein level was markedly elevated. Computed tomography showed expanding right lower lobe lung nodules. Histopathology of the cutaneous biopsy revealed features of a poorly differentiated basaloid carcinoma. Immunohistochemical staining was diffusely positive for glypican-3, focally positive for arginase-1, and negative for hepatocyte paraffin 1. Albumin in situ hybridization was diffusely positive, clinching the diagnosis of HCC. Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.
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Affiliation(s)
- Andrew J Gauger
- Departments of Pathology, and Dermatology, Indiana University School of Medicine, Indianapolis, IN
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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-Like Lesions. MACSWEEN'S PATHOLOGY OF THE LIVER 2024:842-946. [DOI: 10.1016/b978-0-7020-8228-3.00013-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Lin F. A Diagnostic Immunohistochemistry Update: Subspecialties in Anatomic Pathology. Arch Pathol Lab Med 2023; 147:1360-1363. [PMID: 38010359 DOI: 10.5858/arpa.2023-0171-ed] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 11/29/2023]
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Bakhshwin A, Lai KK, Ammoun A, Friedman K, El Hag M. Inhibin-Positive "Cholangioblastic" Variant of Intrahepatic Cholangiocarcinoma: Report of 3 New Patients With Review of the Literature. Int J Surg Pathol 2023; 31:1495-1504. [PMID: 37073447 DOI: 10.1177/10668969231157775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/20/2023]
Abstract
Cholangiocarcinoma is the second most common primary liver malignant neoplasm. It usually affects older individuals in their seventh decade of life with no gender predilection. Recently, a distinct subtype of cholangiocarcinoma has emerged with 2 proposed names: "cholangioblastic" and "solid tubulocystic." This variant predominantly occurs in younger women who lack the common risk factors for patients diagnosed with cholangiocarcinomas, such as older age and chronic liver disease or cirrhosis. We describe 3 new patients with a cholangioblastic variant of intrahepatic cholangiocarcinoma. At the time of diagnosis, the patients were aged 19-, 46-, and 28-year-old; 2 females and 1 male (the 46-year-old). None of our patients had a history of chronic liver disease or known predisposing factors for liver tumors. Tumor size ranged from 2.3 to 23 cm in greatest dimension. Histological examination of these tumors demonstrated reproducible morphology characterized by trabecular, nested, and multicystic patterns with micro and macro follicles filled with eosinophilic material. The immunohistochemical profile showed that the tumor cells were positive for keratin 7, inhibin, synaptophysin, and albumin in situ hybridization, while negative for HepPar1, arginase, and INSM1. All tumors lacked conventional intrahepatic cholangiocarcinoma/adenocarcinoma morphology. We also review the literature and emphasize that neuroendocrine tumors should be recognized as a major diagnostic pitfall of this variant.
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Affiliation(s)
- Ahmed Bakhshwin
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
- King Abdulaziz University, Jeddah, Saudi Arabia
| | - Keith K Lai
- Contra Costa Pathology Associates, Pleasant Hill, CA, USA
| | - Alwalid Ammoun
- Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, USA
| | - Kenneth Friedman
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Mohamed El Hag
- Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
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Kikuchi AT, Umetsu S, Joseph N, Kakar S. Genomic Analysis in the Categorization of Poorly Differentiated Primary Liver Carcinomas. Am J Surg Pathol 2023; 47:1207-1218. [PMID: 37661782 DOI: 10.1097/pas.0000000000002116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
A subset of primary liver carcinomas (PLCs) cannot be classified as hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (iCCA) based on morphology and immunohistochemistry (IHC). This includes tumors with morphology suggestive of HCC but lacking hepatocellular marker expression, tumors with ambiguous morphology characterized by co-expression of hepatocellular and cholangiocytic markers, and undifferentiated pleomorphic carcinomas with no discernible line of differentiation on morphology or IHC. This study examines the role of genomic analysis in the categorization of these tumors. Genomic analysis was performed on 16 PLCs that could not be definitely classified as HCC or iCCA based on morphology and IHC using a capture-based next-generation sequencing assay (n=15) or single gene mutational analysis (n=1). Genomic alterations in TERT promoter were seen in 9/16 cases (56%) and strongly favored HCC. Genomic alterations favoring iCCA were seen in 5/16 cases (31%) and included mutations in IDH1 , PBRM1 , BAP1 , and ERBB2 , as well as FGFR2 fusion. Genomic changes were helpful in classifying 14/16 (87%) PLCs. Though not specific, these genomic alterations can provide valuable diagnostic clues in selected morphologically and immunohistochemically unclassifiable cases. Given the important differences in management between HCC and iCCA, routine use of genomic analysis in diagnostically challenging settings should be considered.
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Affiliation(s)
- Alexander T Kikuchi
- Department of Pathology, University of California San Francisco, San Francisco, CA
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Zhang SL, Wang HL. Ancillary tests for hepatobiliary neoplasms: what we know and what we need to know. Hum Pathol 2023; 141:183-200. [PMID: 36775105 DOI: 10.1016/j.humpath.2023.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/29/2023] [Accepted: 02/04/2023] [Indexed: 02/12/2023]
Abstract
Ancillary tests are commonly used in the surgical pathology setting for diagnosing challenging neoplastic diseases of the liver and biliary tract, while histology and clinical correlation remain to be critically important. With continuous discoveries, more and more useful ancillary tests have become available, which can help distinguish between malignant and benign hepatocellular neoplasms, malignant and benign biliary tract entities, and intrahepatic and metastatic carcinomas. This review will focus on existing and emerging biomarkers (such as glutamine synthetase, organic anion transporting polypeptide 1B3, insulin-like growth factor-II mRNA binding protein-3, S100P, SMAD4, enhancer of zeste homolog 2, albumin, hepatocyte nuclear factor-1β, etc.) that can be used for the diagnosis, classification and prognostication of hepatobiliary neoplasms.
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Affiliation(s)
- Sarah L Zhang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine and Ronald Reagan Medical Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA
| | - Hanlin L Wang
- Department of Pathology and Laboratory Medicine, David Geffen School of Medicine and Ronald Reagan Medical Center, University of California at Los Angeles, Los Angeles, CA, 90095, USA.
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Chung YS, Jeon Y, Yoo JE, Chung T, Ryu HJ, Kim H, Rhee H, Park YN. Albumin, filamin-A and cytokeratin 19 help distinguish intrahepatic cholangiocarcinoma from extrahepatic adenocarcinoma. Hepatol Int 2023; 17:77-85. [PMID: 36253584 DOI: 10.1007/s12072-022-10428-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Accepted: 09/17/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND The differential diagnosis of intrahepatic cholangiocarcinomas (iCCAs) from metastatic adenocarcinomas from organs adjacent to the liver (gallbladder, pancreas, and stomach) is difficult due to histopathological similarity and a lack of specific markers. This study aimed to develop a method to differentiate iCCA and adenocarcinomas originated from extrahepatic organs adjacent to the liver. METHODS We retrospectively enrolled surgically resected iCCA (n = 181) and adenocarcinomas from extrahepatic organs (n = 30, n = 28, and n = 38 from gallbladder, pancreas, and stomach, respectively) between 2007 and 2013. The albumin mRNA in situ hybridization (ISH) and immunohistochemistry (IHC) of filamin-A and cytokeratin 19 (CK19) were performed using tissue microarray. Using logistic regression analysis of three markers, iCCA-score was developed, and its diagnostic performance was evaluated. RESULTS The iCCAs were more frequently positive for albumin ISH (23.2% vs. 0%), filamin-A IHC (47.5% vs. 12.5%) and CK19 (68.5% vs. 40.6%) than extrahepatic adenocarcinomas (p < 0.001 for all). The iCCA-score consisting of these three markers was developed, and it showed higher diagnostic performance (area under the curve [AUC], 0.798 vs. 0.616, p < 0.001). Taking an iCCA-score of 2 or higher as the threshold for iCCA, the sensitivity was substantially higher than albumin ISH alone (45.9% and 23.2%, respectively; p < 0.001), but maintained high specificity (94.8% and 100%, respectively). CONCLUSION Albumin ISH and IHC staining for filamin-A and CK19 showed distinct expression patterns between iCCA and extrahepatic adenocarcinomas from gallbladder, pancreas, and stomach. We developed iCCA-score that consisted of those three markers, and it showed better diagnostic performance than albumin ISH alone.
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Affiliation(s)
- Yeon Seung Chung
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Youngsic Jeon
- Natural Products Research Center, Korea Institute of Science and Technology (KIST), Gangneung-si, Gangwon-do, Korea
| | - Jeong Eun Yoo
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.,Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea
| | - Taek Chung
- Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Korea
| | - Hyang Joo Ryu
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyunki Kim
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hyungjin Rhee
- Department of Radiology, Research Institute of Radiological Science, Center for Clinical Imaging Data Science, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
| | - Young Nyun Park
- Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. .,Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, Korea.
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Wang X, Xiang H, Toyoshima Y, Shen W, Shichi S, Nakamoto H, Kimura S, Sugiyama K, Homma S, Miyagi Y, Taketomi A, Kitamura H. Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells. Cancer Metab 2023; 11:1. [PMID: 36639644 PMCID: PMC9838026 DOI: 10.1186/s40170-022-00301-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 12/14/2022] [Indexed: 01/14/2023] Open
Abstract
BACKGROUND Arginase-1 (ARG1), a urea cycle-related enzyme, catalyzes the hydrolysis of arginine to urea and ornithine, which regulates the proliferation, differentiation, and function of various cells. However, it is unclear whether ARG1 controls the progression and malignant alterations of colon cancer. METHODS We established metastatic colonization mouse model and ARG1 overexpressing murine colon cancer CT26 cells to investigate whether activation of ARG1 was related to malignancy of colon cancer cells in vivo. Living cell numbers and migration ability of CT26 cells were evaluated in the presence of ARG inhibitor in vitro. RESULTS Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular L-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. CONCLUSION Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy.
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Affiliation(s)
- Xiangdong Wang
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan
| | - Huihui Xiang
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan ,grid.414944.80000 0004 0629 2905Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, 241-8515 Japan
| | - Yujiro Toyoshima
- grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Weidong Shen
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan
| | - Shunsuke Shichi
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan ,grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Hiroki Nakamoto
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan ,grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Saori Kimura
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan ,grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Ko Sugiyama
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan ,grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Shigenori Homma
- grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Yohei Miyagi
- grid.414944.80000 0004 0629 2905Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, 241-8515 Japan
| | - Akinobu Taketomi
- grid.39158.360000 0001 2173 7691Department of Gastroenterological Surgery I, Hokkaido University Graduate School of Medicine, Sapporo, 060-8638 Japan
| | - Hidemitsu Kitamura
- grid.39158.360000 0001 2173 7691Division of Functional Immunology, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-0815 Japan
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Lyon PRP, Trevathan S, Talukdar R, Nguyen DD, McPhaul CM, Rampisela D. A Rare Case of Metastatic Hepatocellular Carcinoma to the Hard Palate. J Investig Med High Impact Case Rep 2022; 10:23247096221133989. [PMID: 36300426 PMCID: PMC9619851 DOI: 10.1177/23247096221133989] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Extrahepatic metastasis of hepatocellular carcinoma (HCC) to the head and neck is
unusual, especially the oral cavity/maxillofacial region. Metastatic HCC to the
hard palate, however, is particularly rare. The most common site of HCC
metastasis is the lung, followed by lymph nodes, bone, and adrenal gland.
Importantly, oral cavity metastatic HCC may be misdiagnosed as a primary
malignancy, such as a salivary gland carcinoma. In this article, we describe a
young woman with metastatic HCC to the hard palate that was initially diagnosed
as an acinic cell carcinoma.
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Affiliation(s)
| | | | | | | | | | - Debby Rampisela
- Baylor Scott & White Health,
Temple, TX, USA,Debby Rampisela, MD, Department of
Pathology and Laboratory Medicine, Baylor Scott & White Health, MS-01-266,
2401 S. 31st Street, Temple, TX 76508, USA.
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10
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Identification of novel prognostic risk signature of breast cancer based on ferroptosis-related genes. Sci Rep 2022; 12:13766. [PMID: 35962042 PMCID: PMC9374692 DOI: 10.1038/s41598-022-18044-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 08/04/2022] [Indexed: 12/05/2022] Open
Abstract
Ferroptosis is a type of cell regulated necrosis triggered by intracellular phospholipid peroxidation, which is more immunogenic than apoptosis. Therefore, genes controlling ferroptosis may be promising candidate biomarkers for tumor therapy. In this study, we investigate the function of genes associated with ferroptosis in breast cancer (BC) and systematically evaluate the relationship between ferroptosis-related gene expression and prognosis of BC patients from the Cancer Genome Atlas database. By using the consensus clustering method, 1203 breast cancer samples were clustered into two clearly divided subgroups based on the expression of 237 ferroptosis-related genes. Then differentially expressed analysis and least absolute shrinkage and selection operator were used to identify the prognosis-related genes. Furthermore, the genetic risk signature was constructed using the expression of prognosis-related genes. Our results showed that the genetic risk signature can identify patient subgroups with distinct prognosis in either training cohort or validation, and the genetic risk signature was associated with the tumor immune microenvironment. Finally, the Cox regression analysis indicated that our risk signature was an independent prognostic factor for BC patients and this signature was verified by the polymerase chain reaction and western blot. Within this study, we identified a novel prognostic classifier based on five ferroptosis-related genes which may provide a new reference for the treatment of BRCA patients.
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Wang N, Gu Y, Li L, Chi J, Liu X, Xiong Y, Zhong C. Development and Validation of a Prognostic Classifier Based on Lipid Metabolism-Related Genes for Breast Cancer. J Inflamm Res 2022; 15:3477-3499. [PMID: 35726216 PMCID: PMC9206459 DOI: 10.2147/jir.s357144] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Accepted: 06/07/2022] [Indexed: 11/23/2022] Open
Abstract
Background The changes of lipid metabolism have been implicated in the development of many tumors, but its role in breast invasive carcinoma (BRCA) remains to be fully established. Here, we attempted to ascertain the prognostic value of lipid metabolism-related genes in BRCA. Methods We obtained RNA expression data and clinical information for BRCA and normal samples from public databases and downloaded a lipid metabolism-related gene set. Ingenuity Pathway Analysis (IPA) was applied to identify the potential pathways and functions of Differentially Expressed Genes (DEGs) related to lipid metabolism. Subsequently, univariate and multivariate Cox regression analyses were utilized to construct the prognostic gene signature. Functional enrichment analysis of prognostic genes was achieved by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Kaplan-Meier analysis, Receiver Operating Characteristic (ROC) curves, clinical follow-up results were employed to assess the prognostic potency. Potential compounds targeting prognostic genes were screened by Connectivity Map (CMap) database and a prognostic gene-drug interaction network was constructed using Comparative Toxicogenomics Database (CTD). Furthermore, we separately validated the selected marker genes in BRCA samples and human breast cancer cell lines (MCF-7, MDA-MB-231). Results IPA and functional enrichment analysis demonstrated that the 162 lipid metabolism-related DEGs we obtained were involved in many lipid metabolism and BRCA pathological signatures. The prognostic classifier we constructed comprising SDC1 and SORBS1 can serve as an independent prognostic marker for BRCA. CMap filtered 37 potential compounds against prognostic genes, of which 16 compounds could target both two prognostic genes were identified by CTD. The functions of the two prognostic genes in breast cancer cells were verified by cell function experiments. Conclusion Within this study, we identified a novel prognostic classifier based on two lipid metabolism-related genes: SDC1 and SORBS1. This result highlighted a new perspective on the metabolic exploration of BRCA.
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Affiliation(s)
- Nan Wang
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Yuanting Gu
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Lin Li
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Jiangrui Chi
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Xinwei Liu
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Youyi Xiong
- Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
| | - Chaochao Zhong
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People's Republic of China
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Association between Immunohistochemistry Markers and Tumor Features and Their Diagnostic and Prognostic Values in Intrahepatic Cholangiocarcinoma. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:8367395. [PMID: 35529254 PMCID: PMC9071873 DOI: 10.1155/2022/8367395] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Revised: 02/14/2022] [Accepted: 02/22/2022] [Indexed: 12/28/2022]
Abstract
This study investigated the expression of some frequently used immunohistochemistry (IHC) markers. Besides, we evaluated their correlations with the clinical features and outcomes of intrahepatic cholangiocarcinoma (ICC). Patients who underwent surgical removal of the ICC tumors were followed up for 4 years. The paraffin-embedded sections were used to obtain different markers, including CK7, CK19, CK20, CDX2, Glypican3, Hepa1, Ki-67, Villin, and SATB1. Overall survival in relation to IHC marker expression patterns and other clinical characteristics was evaluated by Kaplan-Meier survival curve and log-rank test, followed by the Cox proportional hazard model (to evaluate the relationship between multiple factors and the overall postoperative survival). A total of 122 ICC patients (67 males and 55 females, averagely aged 57.75) were included in this study. There were 44 cases with vascular invasion, 46 cases with lymphatic metastasis, and 13 cases with distant metastasis. CK7 was negatively correlated with lymphatic metastasis; and in distant-metastasis cases, the positive ratio of SATB1 was lower. Interestingly, SATB1 expression indicated a poorer survival, while Villin expression was associated with a better survival. The COX regression analysis showed that female was a protective factor versus male, Villin expression was a strong protective factor, and Ki-67 expression was correlated with a poor survival. Together, IHC markers are associated with tumor features and postoperative survival, especially for SATB1 as a risk factor and Villin as a protective marker, and female ICC patients may have better survival than males.
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13
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Chung T, Park YN. Up-to-Date Pathologic Classification and Molecular Characteristics of Intrahepatic Cholangiocarcinoma. Front Med (Lausanne) 2022; 9:857140. [PMID: 35433771 PMCID: PMC9008308 DOI: 10.3389/fmed.2022.857140] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 03/07/2022] [Indexed: 12/26/2022] Open
Abstract
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive primary liver malignancy with an increasing incidence worldwide. Recently, histopathologic classification of small duct type and large duct type iCCA has been introduced. Both these types of tumors exhibit differences in clinicopathological features, mutational profiles, and prognosis. Small duct type iCCA is composed of non-mucin-producing cuboidal cells, whereas large duct type iCCA is composed of mucin-producing columnar cells, reflecting different cells of origin. Large duct type iCCA shows more invasive growth and poorer prognosis than small duct type iCCA. The background liver of small duct type iCCA often shows chronic liver disease related to hepatitis B or C viral infection, or alcoholic or non-alcoholic fatty liver disease/steatohepatitis, in contrast to large duct type iCCA that is often related to hepatolithiasis and liver fluke infection. Cholangiolocarcinoma is a variant of small duct type iCCA composed of naïve-looking cuboidal cells forming cords or ductule-like structures, and shows better prognosis than the conventional small duct type. Fibrous tumor stroma, one of the characteristic features of iCCA, contains activated fibroblasts intermixed with innate and adaptive immune cells. The types of stroma (mature versus immature) are related to tumor behavior and prognosis. Low tumor-infiltrating lymphocyte density, KRAS alteration, and chromosomal instability are related to immune-suppressive tumor microenvironments with resistance to programmed death 1/ programmed death ligand 1 blockade. Data from recent large-scale exome analyses have revealed the heterogeneity in the molecular profiles of iCCA, showing that small duct type iCCA exhibit frequent BAP1, IDH1/2 hotspot mutations and FGFR2 fusion, in contrast to frequent mutations in KRAS, TP53, and SMAD4 observed in large duct type iCCA. Multi-omics analyses have proposed several molecular classifications of iCCA, including inflammation class and proliferation class. The inflammation class is enriched in inflammatory signaling pathways and expression of cytokines, while the proliferation class has activated oncogenic growth signaling pathways. Diverse pathologic features of iCCA and its associated multi-omics characteristics are currently under active investigation, thereby providing insights into precision therapeutics for patients with iCCA. This review provides the latest knowledge on the histopathologic classification of iCCA and its associated molecular features, ranging from tumor microenvironment to genomic and transcriptomic research.
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Affiliation(s)
- Taek Chung
- Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea
| | - Young Nyun Park
- Department of Pathology, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul, South Korea
- *Correspondence: Young Nyun Park,
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Lennartz M, Gehrig E, Weidemann S, Gorbokon N, Menz A, Büscheck F, Hube-Magg C, Hinsch A, Reiswich V, Höflmayer D, Fraune C, Jacobsen F, Bernreuther C, Lebok P, Sauter G, Wilczak W, Steurer S, Burandt E, Marx AH, Simon R, Krech T, Clauditz TS, Minner S, Dum D, Uhlig R. Large-Scale Tissue Microarray Evaluation Corroborates High Specificity of High-Level Arginase-1 Immunostaining for Hepatocellular Carcinoma. Diagnostics (Basel) 2021; 11:diagnostics11122351. [PMID: 34943588 PMCID: PMC8699869 DOI: 10.3390/diagnostics11122351] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 12/01/2021] [Accepted: 12/09/2021] [Indexed: 12/19/2022] Open
Abstract
Arginase-1 catalyzes the conversion of arginine to ornithine and urea. Because of its predominant expression in hepatocytes, it serves as a marker for hepatocellular carcinoma, although other tumor entities can also express arginase-1. To comprehensively determine arginase-1 expression in normal and neoplastic tissues, tissue microarrays containing 14,912 samples from 117 different tumor types and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. In normal tissues, arginase-1 was expressed in the liver, the granular layer of the epidermis, and in granulocytes. Among tumors, a nuclear and cytoplasmic arginase-1 immunostaining was predominantly observed in hepatocellular carcinoma, where 96% of 49 cancers were at least moderately positive. Although 22 additional tumor categories showed occasional arginase immunostaining, strong staining was exceedingly rare in these entities. Staining of a few tumor cells was observed in squamous cell carcinomas of various sites. Staining typically involved maturing cells with the beginning of keratinization in these tumors and was significantly associated with a low grade in 635 squamous cell carcinomas of various sites (p = 0.003). Teratoma, urothelial carcinoma and pleomorphic adenomas sometimes also showed arginase expression in areas with squamous differentiation. In summary, arginase-1 immunohistochemistry is highly sensitive and specific for hepatocellular carcinoma if weak and focal staining is disregarded.
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Affiliation(s)
- Maximilian Lennartz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Eva Gehrig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Sören Weidemann
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Natalia Gorbokon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Anne Menz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Franziska Büscheck
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Claudia Hube-Magg
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Andrea Hinsch
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Viktor Reiswich
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Doris Höflmayer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Christoph Fraune
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Christian Bernreuther
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Patrick Lebok
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Eike Burandt
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Andreas H. Marx
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
- Department of Pathology, Academic Hospital Fuerth, 90766 Fuerth, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
- Correspondence: ; Tel.: +49-40-74105-7214
| | - Till Krech
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
- Institute of Pathology, Clinical Center Osnabrueck, 49076 Osnabrueck, Germany
| | - Till S. Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - David Dum
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
| | - Ria Uhlig
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany; (M.L.); (E.G.); (S.W.); (N.G.); (A.M.); (F.B.); (C.H.-M.); (A.H.); (V.R.); (D.H.); (C.F.); (F.J.); (C.B.); (P.L.); (G.S.); (W.W.); (S.S.); (E.B.); (A.H.M.); (T.K.); (T.S.C.); (S.M.); (D.D.); (R.U.)
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Arora K, Kulkarni A, Pankaj A, Desai N, Deshpande V. IgG4 Related Disease is characterized by the overexpression of Immunomodulatory proteins. Histopathology 2021; 81:486-495. [PMID: 34506637 DOI: 10.1111/his.14564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
INTRODUCTION IgG4 related disease (IgG4-RD) is a multisystem disease, characterized by tumefactive lesions and a swift response to immunosuppressive therapy. Although elevated serum and tissue IgG4 are characteristic, T-cells appear to be the primary driver of this immunologically mediated disease. The overarching goal was to examine the role of immunomodulatory cells in IgG4-RD. METHODS Biopsies from patients with IgG4-RD (n=39) and mimics of this disease (n=78) were evaluated for IgG4, IgG, CD8, PD-L1 and a subset (n=18) evaluated for CD4, PU.1, Foxp3, PD-L1, PD-1, IDO1 and LAG3. Data pertaining to demographics and laboratory findings at baseline evaluation was extracted from electronic medical records. RESULTS When compared to mimics, IgG4-RD showed increased numbers of PD-L1 (p=0.0001), PD-1 (p=0.001), IDO1 (p=0.03), LAG3 (p=0.04) and Foxp3 (p=0.04) positive immune cells. The PD-L1 positive cells were enriched within aggregates of CD4 and CD8 positive T-cells. 31 of 39 (80%) IgG4-RD cases showed greater than 5 PD-L1 positive cells per HPF, while 4 of 78 (5%) mimics of this disease exceeded this cut point. In IgG4-RD PD-L1 positive macrophages correlated with PD-1 (p=0.002), LAG3 (p=0.001) and IDO1 positive cells (p=0.001); a positive correlation was also noted between IgG4/IgG ratio and PD-L1, PD-1, and IDO1 positive cells. CONCLUSIONS IgG4-RD shows expansion of mechanisms that maintain peripheral tolerance. The spatial and temporal relationship between T-cells and the PD-L1-PD1 axis, and the upregulation of multiple immunomodulatory proteins suggests that these immunoregulatory mechanisms play a significant role in IgG4-RD.
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Affiliation(s)
- Kshitij Arora
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02478, USA
| | - Anupriya Kulkarni
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02478, USA
| | - Amaya Pankaj
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02478, USA
| | - Niyati Desai
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02478, USA
| | - Vikram Deshpande
- Department of Pathology, Massachusetts General Hospital, Boston, MA, 02478, USA
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Shi C, Jug R, Bean SM, Jeck WR, Guy CD. Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation. Hum Pathol 2021; 116:63-72. [PMID: 34310982 DOI: 10.1016/j.humpath.2021.07.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 06/25/2021] [Accepted: 07/19/2021] [Indexed: 12/17/2022]
Abstract
Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. Electronic medical records were reviewed for clinical history, imaging findings, laboratory results, and follow-up. Pathology slides, immunohistochemistry, and ancillary studies were reviewed. There were two females and two males with age ranging from 52 to 74 years. There was one amphicrine carcinoma with tumor cells simultaneously demonstrating both hepatocellular and neuroendocrine differentiation, one mixed hepatocellular-neuroendocrine carcinoma (NEC) with hepatocellular component intermingled with neuroendocrine component, one small cell NEC, and one well-differentiated neuroendocrine tumor. Next- generation sequencing of the mixed hepatocellular-NEC and small cell NEC showed molecular/genetic alterations commonly seen in hepatocellular carcinoma (HCC). All four cases arose in a background of cirrhosis. Primary hepatic neoplasms arising in cirrhotic livers can have a spectrum of neuroendocrine differentiation. Presence of a NEC component may be an indicator of aggressiveness. In addition, primary hepatic carcinomas with neuroendocrine differentiation likely share the same molecular pathways as HCC.
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Affiliation(s)
- Chanjuan Shi
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
| | - Rachel Jug
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
| | - Sarah M Bean
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
| | - William R Jeck
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
| | - Cynthia D Guy
- Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA
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Wen KW, Joseph NM, Srivastava A, Saunders TA, Jain D, Rank J, Feely M, Zarrinpar A, Al Diffalha S, Shyn PB, Graham RP, Drage MG, Kakar S. Inhibin-positive hepatic carcinoma: proposal for a solid-tubulocystic variant of intrahepatic cholangiocarcinoma. Hum Pathol 2021; 116:82-93. [PMID: 34298064 DOI: 10.1016/j.humpath.2021.07.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Revised: 07/02/2021] [Accepted: 07/10/2021] [Indexed: 01/13/2023]
Abstract
Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord-stromal tumor and thyroid follicular tumors. The term "cholangioblastic variant of intrahepatic cholangiocarcinoma" has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor. Albumin in situ hybridization (ISH) and capture-based next-generation sequencing (NGS) were also performed. All tumors occurred in young women (mean age 32.5 years, range 19-44 years) as a solitary large mass (mean 15.8 cm, range 6.9-23.5 cm). All tumors showed a highly distinctive morphology with sheets and large nests of tumor cells alternating with tubular and cystic areas imparting a sex cord-like or thyroid follicle-like morphology. Cytologic atypia was mild, and mitotic activity was low. All cases were positive for inhibin, as well as pancytokeratin, CK7, CK19, and albumin ISH. Synaptophysin and chromogranin showed focal or patchy staining, whereas INSM1 was negative. Markers for hepatocellular differentiation, thyroid origin, and sex cord-stromal tumor were negative. There were no recurrent genomic changes based on capture-based NGS of ∼500 cancer genes. Recurrence and/or metastasis was seen in three (50%) cases (follow-up time range for all cases: 5 months to 2 years). In conclusion, this series describes the distinctive morphology, immunophenotypic features, and diffuse albumin staining in six cases of a rare inhibin-positive primary liver carcinoma that runs an aggressive course similar to intrahepatic cholangiocarcinoma. Genomic changes typical of cholangiocarcinoma or hepatocellular carcinoma were not identified, and there were no recurrent genetic abnormalities. We propose the term "solid-tubulocystic variant of intrahepatic cholangiocarcinoma" to reflect the spectrum of morphologic patterns observed in this tumor.
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Affiliation(s)
- Kwun Wah Wen
- Department of Pathology, University of California, San Francisco, San Francisco, CA 91343, United States
| | - Nancy M Joseph
- Department of Pathology, University of California, San Francisco, San Francisco, CA 91343, United States
| | - Amitabh Srivastava
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
| | - Tara A Saunders
- Department of Pathology, University of California, San Francisco, San Francisco, CA 91343, United States
| | - Dhanpat Jain
- Department of Pathology, Yale University, New Haven, CT 06520, United States
| | - Joseph Rank
- Cellnetix Pathology & Laboratories, Seattle, WA 98104, United States
| | - Michael Feely
- Department of Pathology, University of Florida, Gainesville, FL 32610, United States
| | - Ali Zarrinpar
- Department of Surgery, University of Florida, Gainesville, FL 32610, United States
| | - Sameer Al Diffalha
- Department of Pathology, University of Alabama, Birmingham, AL 35294, United States
| | - Paul B Shyn
- Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, United States
| | - Rondell P Graham
- Department of Pathology, Mayo Medical Laboratories, Rochester, MN 55901, United States
| | - Michael G Drage
- Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14642, United States
| | - Sanjay Kakar
- Department of Pathology, University of California, San Francisco, San Francisco, CA 91343, United States.
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MYB RNA In Situ Hybridization Facilitates Sensitive and Specific Diagnosis of Adenoid Cystic Carcinoma Regardless of Translocation Status. Am J Surg Pathol 2021; 45:488-497. [PMID: 33165092 DOI: 10.1097/pas.0000000000001616] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Adenoid cystic carcinoma (AdCC) can demonstrate histologic and immunohistochemical (IHC) overlap with a wide range of salivary and nonsalivary tumors, especially in small biopsy specimens. While MYB fluorescence in situ hybridization (FISH) frequently is used to confirm the diagnosis of AdCC, the pathognomonic MYB-NFIB fusion is only present in 40% to 70% of cases. Likewise, although MYB RNA overexpression is seen in the vast majority of AdCC regardless of translocation status, MYB IHC has shown suboptimal specificity for this diagnosis. In this study, we sought to determine whether a novel chromogenic RNA in situ hybridization (ISH) platform could directly detect MYB RNA overexpression and offer a rapid diagnostic adjunct for AdCC. We performed MYB RNA ISH on 84 cases of AdCC as well as 128 other salivary tumors and 108 basaloid and sinonasal carcinomas that mimic AdCC. MYB RNA ISH was 92% sensitive for AdCC, including 97% of cases with MYB rearrangement and 83% without MYB rearrangement by FISH. It was also 89% specific for AdCC overall, with 95% specificity among other salivary tumors and 81% specificity in basaloid and sinonasal carcinomas. In contrast, MYB IHC was 94% sensitive but just 54% specific for AdCC. Overall, MYB RNA ISH provides superior sensitivity for the diagnosis of AdCC compared with MYB FISH and superior specificity compared with MYB IHC. This assay could provide a useful tool for rapidly confirming the diagnosis of AdCC in formalin-fixed, paraffin-embedded specimens.
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Hissong E, Chiu K, Park H, Solomon J, Song W, Jessurun J. Thyroid-Like Cholangiocarcinoma: Histopathological, Immunohistochemical, In-Situ Hybridization and Molecular Studies on an Uncommon Emerging Entity. Int J Surg Pathol 2021; 29:920-925. [PMID: 33939475 DOI: 10.1177/10668969211013906] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Thyroid-like cholangiocarcinoma is a very uncommon variant of peripheral-type cholangiocarcinoma. To date, only 4 prior cases have been reported. The molecular features of this tumor have not been described. We report a case of a 60-year-old woman with a tumor that evolved over a period of 10 years. A left hepatectomy specimen showed an 11 cm tumor that on histology exhibited areas reminiscent of a thyroid tumor with follicular and insular features which were positive on immunohistochemistry for cytokeratin 7 and in-situ hybridization for albumin. A detailed molecular analysis failed to show mutations common to cholangiocarcinomas but revealed frameshift mutations in 2 chromatin-remodeling genes, CREBBP and KMNT2A. This case confirms that thyroid-like cholangiocarcinoma is a histologic variant of this tumor that is associated with relatively low growth. As most cholangiocarcinomas, it is diffusely positive for cytokeratin 7 and albumin by in-situ hybridization. Given its rarity, the molecular alterations in this specific histologic subtype remain to be fully elucidated.
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Affiliation(s)
| | - Kenrry Chiu
- New York Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - Hyeon Park
- New York Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - James Solomon
- New York Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - Wei Song
- New York Presbyterian-Weill Cornell Medicine, New York, NY, USA
| | - Jose Jessurun
- New York Presbyterian-Weill Cornell Medicine, New York, NY, USA
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Hrudka J, Prouzová Z, Mydlíková K, Jedličková K, Holešta M, Whitley A, Havlůj L. FOXF1 as an Immunohistochemical Marker of Hilar Cholangiocarcinoma or Metastatic Pancreatic Ductal Adenocarcinoma. Single Institution Experience. Pathol Oncol Res 2021; 27:1609756. [PMID: 34257615 PMCID: PMC8262193 DOI: 10.3389/pore.2021.1609756] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/17/2021] [Indexed: 12/28/2022]
Abstract
Cholangiocarcinoma (CCA) is a liver malignancy associated with a poor prognosis. Its main subtypes are peripheral/intrahepatic and hilar/extrahepatic CCA. Several molecular, morphological and clinical similarities between hilar/extrahepatic CCA and pancreatic ductal adenocarcinoma (PDAC) have been described. FOXF1 is a transcription factor which has been described to have prognostic significance in various tumors and it is involved in the development of bile ducts. The aim of this study is to determine occurrence of nuclear expression of FOXF1 in both subtypes of CCA and metastatic PDAC and assess its potential usefulness as a diagnostic marker. Secondary aims were to investigate the use of C-reactive protein (CRP) immunohistochemistry for diagnosing intrahepatic peripheral CCA and the significance of histological features in CCA subtypes. 32 archive specimens of CCA, combined hepatocellular carcinoma-CCA (HCC-CCA) and liver metastasis of PDAC were stained by FOXF1 and CRP immunohistochemistry and evaluated to determine histological pattern. The CCAs were classified radiologically into peripheral/intrahepatic and hilar subtype. Using Fisher exact test, we identified nuclear FOXF1 as a fairly specific (87%) but insensitive (65%) marker of hilar and extrahepatic CCA and metastatic PDAC (p = 0.005). CRP immunohistochemistry was characterized by a high sensitivity and specificity, of 79% and 88%, respectively (p = 0.001). We did not identify any histomorphological features associated with either types of CCA or metastatic PDAC. As a conclusion of novel finding, FOXF1 immunohistochemistry may be regarded as a specific but insensitive marker of hilar/extrahepatic CCA and metastatic PDAC and it may help distinguish them from peripheral CCA.
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Affiliation(s)
- Jan Hrudka
- Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Zuzana Prouzová
- Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Katarína Mydlíková
- Department of Pathology, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Kristína Jedličková
- Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Michal Holešta
- Department of Radiodiagnostics, Charles University, 3rd Faculty of Medicine, Charles University and Královské Vinohrady University Hospital, Prague, Czech Republic
| | - Adam Whitley
- Department of General Surgery, Charles University, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, Prague, Czech Republic
| | - Lukáš Havlůj
- Department of General Surgery, Charles University, 3rd Faculty of Medicine, Charles University, University Hospital Královské Vinohrady, Prague, Czech Republic
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Ceausu M, Socea B, Serban D, Smarandache CG, Predescu D, Bacalbaşa N, Slavu I, Tulin A, Alecu L, Ceauşu Z. Heterogeneity of antigenic constellation in human hepatocellular carcinoma. Exp Ther Med 2021; 21:270. [PMID: 33603877 PMCID: PMC7851646 DOI: 10.3892/etm.2021.9701] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Accepted: 11/24/2020] [Indexed: 12/13/2022] Open
Abstract
Hepatocellular carcinoma is one of the primary liver malignancies responsible for over a million deaths per year worldwide (approximately 10% of all deaths in the adult age range). The diagnosis of HCC can be difficult and often requires the use of more than one microscopic technique. A retrospective study was performed on a study batch of 42 cases that died of HCC due to metastasis or other secondary complications. Tissue samples were taken in order to investigate the tumour antigenic constellation by means of IHC method using a large variety of antibodies. In situ hybridization was also performed for albumin mRNA to assess the albumin expression in some selected cases. Telomerase activity was investigated using IHC method for the hTERT catalytic subunit. A cocktail of hepatic cytokeratins (CK8, 18) combined with Hep Par-1 and associated to albumin proved to be more powerful than albumin alone in differentiating HCC and increased the value of tumour diagnosis. hTERT expression was proportionally reverse to the tumour degree of differentiation, but was independent from the expression of tumour-proliferating indexes. The heterogeneity of the antigenic constellation in hepatocellular carcinoma suggests an antigenic mosaicism, which can be expressed a synchronous or metachronous manner, depending on the tumour degree of differentiation.
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Affiliation(s)
- Mihai Ceausu
- Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Bogdan Socea
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
| | - Dragos Serban
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- IVth Department of Surgery, University Emergency Hospital, 050098 Bucharest, Romania
| | - Cătălin Gabriel Smarandache
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- IVth Department of Surgery, University Emergency Hospital, 050098 Bucharest, Romania
| | - Dragoş Predescu
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, ‘Sf. Maria’ Hospital, 011172 Bucharest, Romania
| | - Nicolae Bacalbaşa
- Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Obstetrics and Gynecology, ‘Dr. I. Cantacuzino’ Clinical Hospital, 030167 Bucharest, Romania
| | - Iulian Slavu
- Department of Surgery, ‘Prof. Dr. Agrippa Ionescu’ Clinical Emergency Hospital, 011356 Bucharest, Romania
| | - Adrian Tulin
- Department of Surgery, ‘Prof. Dr. Agrippa Ionescu’ Clinical Emergency Hospital, 011356 Bucharest, Romania
- Department of Anatomy, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Lucian Alecu
- Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania
- Department of Surgery, ‘Prof. Dr. Agrippa Ionescu’ Clinical Emergency Hospital, 011356 Bucharest, Romania
| | - Zenaida Ceauşu
- Pathology Department, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
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22
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Avadhani V, Cohen C, Siddiqui MT, Krasinskas A. A Subset of Intrahepatic Cholangiocarcinomas Express Albumin RNA as Detected by In Situ Hybridization. Appl Immunohistochem Mol Morphol 2021; 29:175-179. [PMID: 33181516 DOI: 10.1097/pai.0000000000000882] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2020] [Accepted: 10/07/2020] [Indexed: 12/28/2022]
Abstract
Intrahepatic cholangiocarcinomas (ICCs) show morphologic diversity, ranging from tumors composed of nonmucinous small ducts to mucin-producing large duct tumors to tumors with mixed hepatocellular carcinoma features. Diagnosing ICCs can be difficult, especially on biopsy, not only because of the morphologic diversity, but also because metastatic tumors are often in the differential diagnosis. Recently, branched DNA-based albumin RNA in situ hybridization (ISH) has been shown to be a potential sensitive and specific marker for ICC with 99% sensitivity. Using a different RNA ISH technology, we evaluated the expression of albumin RNA ISH in ICC. We performed RNA ISH for albumin using RNAscope on 43 ICCs in a triplicate tissue microarray. Albumin RNA ISH was positive in 18 of 43 (42%) ICCs. Five of the 6 (83%) combined hepatocellular carcinoma-CC were positive in the CC component. None of the tumors with mucin production were positive (0/9). In our cohort, albumin RNA ISH showed a sensitivity of 42% in ICCs, supporting the morphologic diversity of ICCs. Albumin RNA ISH does not appear to be a highly sensitive marker for ICC and hence cannot be used as a stand-alone marker for ICC.
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Affiliation(s)
- Vaidehi Avadhani
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA
| | - Cynthia Cohen
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA
| | - Momin T Siddiqui
- Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York City, NY
| | - Alyssa Krasinskas
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA
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23
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Wang W, Li Q, Huang G, Lin BY, Lin D, Ma Y, Zhang Z, Chen T, Zhou J. Tandem Mass Tag-Based Proteomic Analysis of Potential Biomarkers for Hepatocellular Carcinoma Differentiation. Onco Targets Ther 2021; 14:1007-1020. [PMID: 33603407 PMCID: PMC7886252 DOI: 10.2147/ott.s273823] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 01/28/2021] [Indexed: 01/27/2023] Open
Abstract
Purpose The poor prognosis of hepatocellular carcinoma (HCC) urgent us to discover early and effective biomarkers. In this study, we applied tandem mass tag (TMT)-based proteomic analysis to discover potential protein markers for HCC identification and differentiation. Patients and Methods Fifteen patients, well-differentiated (G1, N = 5), moderate-differentiated (G2, N = 5), and poorly differentiated (G3, N = 5), with 30 matched pair tissues (both tumor and adjacent non-tumor tissues derived from the same patient) were enrolled. All samples were subjected to TMT labeling and LC−MS/MS analysis. The identified proteins were subsequently assigned to GO and KEGG for predicting function. The identified protein candidates were validated using immunohistochemistry (IHC). Results A total of 1010 proteins were identified. Of these, 154 differentially expressed proteins (DEPs), 100 up-regulated and 54 down-regulated, were found between tumor and adjacent non-tumor tissues; 12 DEPs, 9 up-regulated and 3 down-regulated, were found between G1 and G3 tissues; 8 DEPs, 5 up-regulated and 3 down-regulated, were found between G1 and G2 tissues; 11 DEPs, 8 up-regulated and 3 down-regulated, were found between G2 and G3 tissues. Among them, ASS1 and CPS1 were significantly up-regulated while UROD and HBB were significantly down-regulated in G3 compared with G1 and G2 tumors. Three proteins, CYB5A, FKBP11 and YBX1, were significantly up-regulated in G1 compared with both G2 and G3 tumors. The 7 biomarker candidates were further verified by IHC. Conclusion A variety of DEPs related to the histological differentiation of HCC were identified, among which ASS1, CPS1, URPD and HBB proteins were potential biomarkers for distinguishing poorly differentiated HCC, while CYB5A, FKBP11 and YBX1 were potential biomarkers for distinguishing well-differentiated HCC. Our findings may further provide a new insight facilitating the diagnosis and prognosis of HCC.
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Affiliation(s)
- Wei Wang
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Qiang Li
- Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, 510000, People's Republic of China
| | - Ge Huang
- Intensive Care Unit, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Bing-Yao Lin
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Dongzi Lin
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Yan Ma
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Zhao Zhang
- Research and Development Centre, South China Institute of Biomedicine, Guangdonglongsee Biomedical Co., Ltd, Guangzhou, 510000, People's Republic of China
| | - Tao Chen
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
| | - Jie Zhou
- Department of Laboratory, Foshan Fourth People's Hospital, Foshan, 528000, People's Republic of China
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24
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Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy. Am J Surg Pathol 2021; 44:1581-1590. [PMID: 32826531 DOI: 10.1097/pas.0000000000001568] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-κB ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell-rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell-rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.
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25
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Zhang Y, Archer KJ. Bayesian penalized cumulative logit model for high-dimensional data with an ordinal response. Stat Med 2020; 40:1453-1481. [PMID: 33336826 DOI: 10.1002/sim.8851] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 11/23/2020] [Accepted: 11/23/2020] [Indexed: 01/15/2023]
Abstract
Many previous studies have identified associations between gene expression, measured using high-throughput genomic platforms, and quantitative or dichotomous traits. However, we note that health outcome and disease status measurements frequently appear on an ordinal scale, that is, the outcome is categorical but has inherent ordering. Identification of important genes may be useful for developing novel diagnostic and prognostic tools to predict or classify stage of disease. Gene expression data are usually high-dimensional, meaning that the number of genes is much larger than the sample size or number of patients. Herein we describe some existing frequentist methods for modeling an ordinal response in a high-dimensional predictor space. Following Tibshirani (1996), who described the LASSO estimate as the Bayesian posterior mode when the regression coefficients have independent Laplace priors, we propose a new approach for high-dimensional data with an ordinal response that is rooted in the Bayesian paradigm. We show that our proposed Bayesian approach outperforms existing frequentist methods through simulation studies. We then compare the performance of frequentist and Bayesian approaches using a study evaluating progression to hepatocellular carcinoma in hepatitis C infected patients.
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Affiliation(s)
- Yiran Zhang
- College of Public Health, The Ohio State University, Columbus, Ohio, USA
| | - Kellie J Archer
- College of Public Health, The Ohio State University, Columbus, Ohio, USA
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26
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Utility and Limitations of Albumin mRNA In Situ Hybridization Detection in the Diagnosis of Hepatobiliary Lesions and Metastatic Carcinoma to the Liver. Appl Immunohistochem Mol Morphol 2020; 29:180-187. [PMID: 33208670 DOI: 10.1097/pai.0000000000000885] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 10/14/2020] [Indexed: 12/25/2022]
Abstract
Albumin messenger RNA (mRNA) in situ hybridization is a sensitive and specific biomarker for hepatocellular carcinoma (HCC). Intrahepatic cholangiocarcinoma (ICC) shows variable sensitivity, whereas extrahepatic cholangiocarcinoma (ECC) and metastatic carcinoma are generally negative. We studied the clinical utility and limitations of albumin mRNA detection in a cohort of HCCs, ICCs, ECCs, bile duct adenomas, bile duct hamartomas, and metastatic carcinomas to the liver; and investigated the variability in sensitivity observed for this biomarker in ICCs. We identified 122 cases of hepatobiliary lesions and metastatic carcinomas. Albumin mRNA detection was performed using RNAscope run on formalin-fixed, paraffin-embedded tissue sections. ICCs were categorized according to the classification proposed by Hayashi and colleagues into the small duct, large duct, and indeterminate subtypes. Albumin mRNA was detected in all 17 HCCs and focally in 6/8 (75%) of bile duct adenomas. All 28 nonhepatic carcinomas, 13 bile duct hamartomas, and 9 ECCs were negative. Albumin mRNA was found in 38/47 (80.9%) of ICC with 35/37 (94.6%) in the small duct subtype, 2/3 (66.7%) in the indeterminate subtype, and 1/7 (14.3%) of the large duct subtype (P<0.003). Albumin mRNA detection is a sensitive and specific biomarker for HCCs. It is highly sensitive and moderately specific in the diagnosis of ICC with small gland morphology, but not ICCs with large duct morphology and in metastatic carcinoma. The variability in the sensitivity of albumin mRNA expression in ICCs may depend on the subtypes of ICC.
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27
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Abstract
Hepatocellular carcinoma (HCC) is a morphologically heterogeneous tumor with variable architectural growth patterns and several distinct histologic subtypes. Large-scale attempts have been made over the past decade to identify targetable genomic alterations in HCC; however, its translation into clinical personalized care remains a challenge to precision oncology. The role of pathology is no longer limited to confirmation of diagnosis when radiologic features are atypical. Pathology is now in a position to predict the underlying molecular alteration, prognosis, and behavior of HCC. This review outlines various aspects of histopathologic diagnosis and role of pathology in cutting-edge diagnostics of HCC.
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Affiliation(s)
- Monika Vyas
- Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 303 Brookline Avenue, Boston, MA 02215, USA
| | - Xuchen Zhang
- Department of Pathology, Yale School of Medicine, 310 Cedar Street, PO Box 208023, New Haven, CT 06520-8023, USA.
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28
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Chen DA, Koehne de Gonzalez A, Fazlollahi L, Coffey A, Remotti HE, Lagana SM. In situ hybridisation for albumin RNA in paediatric liver cancers compared with common immunohistochemical markers. J Clin Pathol 2020; 74:98-101. [PMID: 32471888 DOI: 10.1136/jclinpath-2020-206663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/11/2020] [Accepted: 05/12/2020] [Indexed: 11/04/2022]
Abstract
AIMS In situ hybridisation (ISH) for albumin mRNA is a sensitive marker of primary liver tumours in adults. However, paediatric tumours, such as hepatoblastoma (HB) and fibrolamellar hepatocellular carcinoma (FLC), have not been tested thoroughly and may require ancillary tests to diagnose with confidence. We aim to determine if albumin ISH is useful in the pathological evaluation of these malignancies and to compare it to commonly used immunohistochemical markers HepPar 1 (HEPA) and arginase-1 (ARG). METHODS Tissue microarrays of 26 HB and 10 FLC were constructed. Controls included 4 embryonal undifferentiated sarcomas of the liver, 51 neuroblastomas and 64 Wilms tumours. We evaluated a commercially available RNA ISH to detect albumin mRNA. Immunohistochemistry for HEPA and ARG was performed in the usual fashion. RESULTS Twenty-six of 26 HB showed positive staining by albumin ISH including 14 fetal, 8 embryonal and 4 mixed variants. All 10 FLC were diffusely positive. The sensitivity and specificity of albumin ISH were 100% for HB and FLC. ARG had 100% sensitivity and specificity for HB (26 of 26 cases) and FLC (9 of 9). HEPA stained 22 of 26 HB (85% sensitivity, 99.2% specificity) and 7 of 9 FLC (78% sensitivity, 99.1% specificity). CONCLUSION Albumin RNA ISH is a useful test to determine hepatocytic origin in HB and FLC. ARG was equally sensitive and easy to interpret, while HEPA was inferior to both in HB and FLC.
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Affiliation(s)
- Diane Ann Chen
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Anne Koehne de Gonzalez
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Ladan Fazlollahi
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Amy Coffey
- Department of Diagnostic Medicine, University of Texas System, Austin, Texas, USA
| | - Helen E Remotti
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
| | - Stephen M Lagana
- Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York, USA
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Wang X, Xu Y, Wang R, Dai N, Zhang W, Li F. The significance of arginase-1 expression in the diagnosis of liver cancer: A protocol for a systematic review. Medicine (Baltimore) 2020; 99:e19159. [PMID: 32118719 PMCID: PMC7478447 DOI: 10.1097/md.0000000000019159] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Pathologic distinction between HCC and intrahepatic cholangiocarcinoma (ICC) and metastatic adenocarcinoma can be challenging and sometimes requires immunohistochemical panels. Recently, arginase-1 (ARG-1) has been introduced for differentiation of these tumors. METHODS We will search Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure through August 1, 2019, comprehensive collection studies about the diagnostic value of ARG-1 for HCC. Two reviewers will screen literature according to the inclusion and exclusion criteria, extract data, and assess the quality of included studies. Review Manager 5.3 and STATA 15.0 will be used to conduct the meta-analysis. RESULTS The review will provide a high-quality synthesis of current evidence of the diagnostic value of liver cancer. The results will be published in a peer-reviewed journal. CONCLUSION We hope that the results of this study will provide significant evidence to assess the value of ARG-1 in differential diagnosis of HCC, ICC, and metastatic carcinoma of liver.
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30
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MDM2 RNA In Situ Hybridization for the Diagnosis of Atypical Lipomatous Tumor: A Study Evaluating DNA, RNA, and Protein Expression. Am J Surg Pathol 2020; 43:446-454. [PMID: 30520819 DOI: 10.1097/pas.0000000000001199] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The distinction of atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from its benign counterpart, lipoma, may represent a challenge. MDM2 DNA amplification is used as the gold standard as MDM2 immunohistochemistry lacks specificity and sensitivity. Herein, we investigate the diagnostic utility of MDM2 RNA in situ hybridization (RNA-ISH) and compare the test with MDM2 immunohistochemistry and MDM2 DNA fluorescence in situ hybridization (FISH) in benign and malignant lipomatous neoplasms. We evaluated 109 neoplasms including 27 lipomas, 25 spindle cell lipomas, 32 ALTs/WDLs, and 25 dedifferentiated liposarcomas (DDL). The validation cohort included 14 lipoma-like neoplasms that lacked unequivocal features of ALT/WDL and in which MDM2 immunohistochemistry was either equivocal, negative or falsely positive. Immunohistochemistry, automated RNA-ISH and DNA-FISH for MDM2 were performed. Tumors with diffuse nuclear staining or >50 dots per cell on RNA-ISH were considered positive. All lipomas and lipoma variants were negative for RNA-ISH while all ALTs/WDLs and DDLs were positive. Eighty percent (24/30) and 92% (22/24) of ALTs/WDLs and DDLs were positive for MDM2 immunohistochemistry. Lipomas and its variants were negative for MDM2 amplification; 92% and 100% of ALTs/WDLs and DDLs showed MDM2 DNA amplification. The mean percentage of ALT/WDL tumor cells showing MDM2 RNA-ISH positivity was 73% compared with 24% on MDM2 immunohistochemistry. RNA-ISH correctly classified all 10 ALTs/WDLs and all 4 lipomas in the validation cohort. The performance of MDM2 RNA-ISH and MDM2 DNA-FISH are equivalent. MDM2 RNA-ISH can be of diagnostic value in histologically challenging lipomatous neoplasms. The automated MDM2 RNA-ISH assay should allow for more widespread use of MDM2 testing and for a more sensitive and specific diagnosis of ALT/WDL.
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31
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Morphologic Overlap Between Inflammatory Myofibroblastic Tumor and IgG4-related Disease: Lessons From Next-generation Sequencing. Am J Surg Pathol 2020; 43:314-324. [PMID: 30451733 DOI: 10.1097/pas.0000000000001167] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Inflammatory myofibroblastic tumor (IMT), a locally aggressive neoplasm capable of metastasis, may show an immunoglobulin (Ig)G4-rich lymphoplasmacytic infiltrate. Prior reports suggest that storiform-fibrosis and obliterative phlebitis aid in the distinction of IMT from IgG4-related diseases. Herein, we highlight the morphologic overlap between the 2 diseases, and emphasize the importance of a multiplex fusion assay in the distinction of IgG4-related disease (IgG4-RD) from IMT. We identified 7 IMTs with morphologic and immunohistochemical features of IgG4-RD; 3 patients were originally diagnosed with IgG4-RD. Demographic, clinical and morphologic data was recorded. We also reevaluated 56 patients with IgG4-RD. We performed immunohistochemistry for IgG4, IgG, ALK, and ROS1. In situ hybridization for IgG4 and IgG was performed in selected cases. A multiplex next-generation sequencing-based RNA assay for gene fusions was performed to detect all known IMT-related gene fusions. All 7 IMTs showed a dense lymphoplasmacytic infiltrate and storiform-type fibrosis, with obliterative phlebitis noted in 3 cases. The neoplastic stromal cells constituted <5% of overall cellularity and stromal atypia was either absent or focal and mild. Elevated numbers of IgG4 positive cells and increased IgG4 to IgG ratio was identified in all cases. Four cases showed ALK related abnormalities: 3 fusions and one alternative transcription initiation; while 2 patients showed ROS1 and NTRK3 fusions. One tumor was negative for known IMT-related gene fusions. All 56 IgG4-RD cases were negative for ALK and ROS1 on immunohistochemistry; 6 cases were negative on the fusion assay. Highly inflamed IMTs are indistinguishable from IgG4-RD both histologically and on immunohistochemistry for IgG4. We advocate scrutinizing patients with presumptive single organ IgG4-RD for IMT and the diagnostic algorithm should include ALK and ROS1 immunohistochemistry and, in selected cases, a next-generation sequencing-based fusion assay that covers known IMT-associated gene fusions.
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32
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Torbenson M, Washington K. Pathology of liver disease: advances in the last 50 years. Hum Pathol 2019; 95:78-98. [PMID: 31493428 DOI: 10.1016/j.humpath.2019.08.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2019] [Accepted: 08/28/2019] [Indexed: 02/07/2023]
Abstract
Liver disease has been recognized in various forms for centuries. Incredible advances, however, have been made especially in the last 50 years, driven by improvements in histology, the development of immunostains, the development of high resolution imaging methods, improved biopsy and resection methods, and the emergence of the molecular era. With these tools, pathologists and their clinical and basic science colleagues moved from classifying liver disease using an observational, pattern-based approach to a refined classification of disease, one based on etiology for medical disease and tumor classification for neoplastic disease. Examples of liver specific diseases are used to illustrate these exciting advances. These impressive advances of the past provide the foundation for hope in the future, as liver pathology continues to play an important role in improving patient care through disease identification and classification and emerging roles in guiding therapy for cures.
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Affiliation(s)
- Michael Torbenson
- Department of Pathology and Laboratory Medicine, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905.
| | - Kay Washington
- C-3321 MCN, Department of Pathology, Vanderbilt University Medical Center, 1161 21(st) Avenue S, Nashville, TN 37232.
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Intrahepatic Cholangiocarcinomas Have Histologically and Immunophenotypically Distinct Small and Large Duct Patterns. Am J Surg Pathol 2019; 42:1334-1345. [PMID: 30001234 DOI: 10.1097/pas.0000000000001118] [Citation(s) in RCA: 48] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Intrahepatic cholangiocarcinomas are histologically heterogenous. Using a cohort of 184 clinically defined, resected intrahepatic cholangiocarcinomas, we retrospectively classified the histology into 4 subtypes: large duct (LD), small duct (SD) (predominantly tubular [SD1] or predominantly anastomosing/cholangiolar, [SD2]), or indeterminate. Then, we tested the 4 subtypes for associations with risk factors, patient outcomes, histology, and immunophenotypic characteristics. SD was the most common (84%; 24% SD1 and 60% SD2) with lower proportions of LD (8%), and indeterminate (8%). Primary sclerosing cholangitis was rare (2%), but correlated with LD (P=0.005). Chronic hepatitis, frequent alcohol use, smoking, and steatosis had no histologic association. LD was associated with mucin production (P<0.001), perineural invasion (P=0.002), CA19-9 staining (P<0.001), CK7, CK19, CD56 immunophenotype (P=0.005), and negative albumin RNA in situ hybridization (P<0.001). SD was histologically nodular (P=0.019), sclerotic (P<0.001), hepatoid (P=0.042), and infiltrative at the interface with hepatocytes (P<0.001). Albumin was positive in 71% of SD and 18% of LD (P=0.0021). Most albumin positive tumors (85%) lacked extracellular mucin (P<0.001). S100P expression did not associate with subtype (P>0.05). There was no difference in disease-specific or recurrence-free survival among the subtypes. Periductal infiltration and American Joint Committee on Cancer eighth edition pT stage predicted survival by multivariable analysis accounting for gross configuration, pT stage, and histologic type. pT2 had worse outcome relative to other pT stages. Significant differences in histology and albumin expression distinguish LD from SD, but there is insufficient evidence to support further subclassification of SD.
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Brackett DG, Neyaz A, Arora K, Masia R, Mattia A, Zukerberg L, Misdraji J, Goyal L, Zhu AX, Ferrone CR, Yilmaz OH, Deshpande V. Cholangiolar pattern and albumin in situ hybridisation enable a diagnosis of intrahepatic cholangiocarcinoma. J Clin Pathol 2019; 73:23-29. [PMID: 31422372 DOI: 10.1136/jclinpath-2019-206055] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2019] [Revised: 07/29/2019] [Accepted: 07/30/2019] [Indexed: 12/15/2022]
Abstract
AIMS The histological distinction of intrahepatic cholangiocarcinoma (ICC) from metastatic adenocarcinoma remains a challenge. The primary goal was to evaluate the diagnostic value of morphology and albumin expression in the diagnosis of ICC. METHODS We evaluated morphological patterns in 120 ICCs and 677 non-hepatic adenocarcinomas and performed in situ hybridisation (ISH) stain for albumin in the former cohort (retrospective cohort). We also identified 119 samples from primary and metastatic lesions, the validation cohort, in which albumin ISH was performed as part of the diagnostic workup. Targeted sequencing was performed on selected cases. We also mined existing expression profiling data including cases from The Cancer Genome Atlas (TCGA) (41 760 unique samples). RESULTS In the retrospective cohort, 45% of ICCs and <1% of non-hepatic adenocarcinomas showed a cholangiolar pattern; albumin ISH was positive in 93% of ICCs with significant intratumorous heterogeneity. In the validation cohort, 29% of ICCs showed a cholangiolar pattern and 88% expressed albumin, while all metastatic non-hepatic neoplasms were negative (n=37) (sensitivity 88% and specificity 100%). Targetable genetic alterations (IDH mutations and FGFR2 fusions) were identified in 31% of ICCs (10 of 32). An analysis of the TCGA data validated the specificity of the albumin assay. CONCLUSIONS The cholangiolar pattern and albumin RNA ISH distinguishes ICC from metastatic adenocarcinoma with high specificity. Given the high prevalence of targetable mutations in ICC, albumin RNA ISH is an essential component in the workup of tumours of uncertain origin. A specific diagnosis of ICC could trigger molecular testing and uncover targetable genetic alterations.
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Affiliation(s)
- Diane G Brackett
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Azfar Neyaz
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Kshitij Arora
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Ricard Masia
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Anthony Mattia
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lawerence Zukerberg
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Joseph Misdraji
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Lipika Goyal
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Andrew X Zhu
- Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Cristina R Ferrone
- Depatment of General and Gastrointestinal Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Omer H Yilmaz
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Vikram Deshpande
- Depatment of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA
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Nasir A, Lehrke HD, Mounajjed T, Said S, Zhang L, Yasir S, Shah SS, Chandan VS, Smyrk TC, Moreira RK, Boland Froemming JM, Herrera Hernandez LP, Wu TT, Graham RP. Albumin In Situ Hybridization Can Be Positive in Adenocarcinomas and Other Tumors From Diverse Sites. Am J Clin Pathol 2019; 152:190-199. [PMID: 31107526 DOI: 10.1093/ajcp/aqz032] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVES Albumin messenger RNA (mRNA) expression is a marker of hepatocellular differentiation. Most published data are from review of tissue microarrays, and albumin in situ hybridization (ISH) expression across several tumor types is incompletely characterized. METHODS Sections from 221 tumors were evaluated for albumin mRNA. Immunohistochemistry was used to confirm diagnoses. Albumin ISH was performed according to manufacturer-provided instructions. Fifty-nine cases were evaluated with both commercial ISH assays. RESULTS Albumin mRNA was detected in all hepatocellular carcinomas (HCCs) and 81% of intrahepatic cholangiocarcinomas. Lung (20%), gallbladder (39%), hepatoid pancreatic (n = 1 of 1) adenocarcinoma, breast invasive ductal carcinoma (18%), yolk sac tumor (25%), and acinar cell carcinoma (29%) showed expression. Both assays were concordant in 93% of cases. CONCLUSIONS Albumin ISH was expressed in all HCCs studied. It was also positive in intrahepatic cholangiocarcinoma and patchy positive in gallbladder adenocarcinoma and a subset of other neoplasms, which can be a potential pitfall.
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Affiliation(s)
- Aqsa Nasir
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | - Heidi D Lehrke
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | | | - Samar Said
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | - Lizhi Zhang
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | - Saba Yasir
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | - Sejal S Shah
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | | | - Thomas C Smyrk
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
| | | | | | | | - Tsung-Teh Wu
- Division of Anatomic Pathology, Mayo Clinic, Rochester, MN
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Chu YH, Hardin H, Zhang R, Guo Z, Lloyd RV. In situ hybridization: Introduction to techniques, applications and pitfalls in the performance and interpretation of assays. Semin Diagn Pathol 2019; 36:336-341. [PMID: 31227426 DOI: 10.1053/j.semdp.2019.06.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
In situ hybridization (ISH) has become a common laboratory technique used for the analysis of gene expression and for the localization of specific DNA and RNA molecules in cells. Many different methods of performing ISH have been described. These techniques have evolved into important tools in basic scientific research and in clinical diagnoses. One of the goals of ISH is to localize gene sequences in situ and to visualize the products within cells while preserving cell integrity. This allows for meaningful anatomical and histological interpretation of the localized product(s) within heterogeneous tissues. Because of the possibility of false positive and false negative results that may occur with ISH assays, familiarity with the pathophysiology of the molecules that are analyzed and the cellular processes involved as well as with limitations of the assays can help to avoid erroneous diagnoses with clinical specimens.
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Affiliation(s)
- Ying-Hsia Chu
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Hangzhou, China
| | - Heather Hardin
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Hangzhou, China
| | - Ranran Zhang
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Hangzhou, China
| | - Zhenying Guo
- Department of Pathology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Ricardo V Lloyd
- Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Hangzhou, China.
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Giant Cell Lesions of the Maxillofacial Skeleton Express RANKL by RNA In Situ Hybridization Regardless of Histologic Pattern. Am J Surg Pathol 2019; 43:819-826. [DOI: 10.1097/pas.0000000000001257] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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El Jabbour T, Lagana SM, Lee H. Update on hepatocellular carcinoma: Pathologists’ review. World J Gastroenterol 2019; 25:1653-1665. [PMID: 31011252 PMCID: PMC6465943 DOI: 10.3748/wjg.v25.i14.1653] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 03/12/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
Abstract
Histopathologic diversity and several distinct histologic subtypes of hepatocellular carcinoma (HCC) are well-recognized. Recent advances in molecular pathology and growing knowledge about the biology associated with distinct histologic features and immuno-profile in HCC allowed pathologists to update classifications. Improving sub-classification will allow for more clinically relevant diagnoses and may allow for stratification into biologically meaningful subgroups. Therefore, immuno-histochemical and molecular testing are not only diagnostically useful, but also are being incorporated as crucial components in predicting prognosis of the patients with HCC. Possibilities of targeted therapy are being explored in HCC, and it will be important for pathologists to provide any data that may be valuable from a theranostic perspective. Herein, we review and provide updates regarding the pathologic sub-classification of HCC. Pathologic diagnostic approach and the role of biomarkers as prognosticators are reviewed. Further, the histopathology of four particular subtypes of HCC: Steatohepatitic, clear cell, fibrolamellar and scirrhous - and their clinical relevance, and the recent consensus on combined HCC-cholangiocarcinoma is summarized. Finally, emerging novel biomarkers and new approaches to HCC stratification are reviewed.
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Affiliation(s)
- Tony El Jabbour
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, United States
| | - Stephen M Lagana
- Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States
| | - Hwajeong Lee
- Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY 12208, United States
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Arora K, Rivera M, Ting DT, Deshpande V. The histological diagnosis of IgG4-related disease on small biopsies: challenges and pitfalls. Histopathology 2019; 74:688-698. [PMID: 30408214 DOI: 10.1111/his.13787] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 11/05/2018] [Indexed: 12/20/2022]
Abstract
AIMS The pathological diagnosis of IgG4-related disease (IgG4-RD) relies on histology, IgG4-positive cells, and an increased IgG4/IgG ratio. Small biopsies from patients with a presumptive diagnosis of IgG4-RD often fail to meet consensus histological criteria. The aims of this study were to evaluate consecutive small biopsies from patients with a presumptive diagnosis of IgG4-RD, and to assess the significance of the pathological findings. METHODS AND RESULTS We evaluated 55 small biopsies from patients with a presumptive diagnosis of IgG4-RD. The retrospective cohort comprised 71 patients with IgG4-RD and 57 mimics. We performed immunohistochemistry (IHC) and in-situ hybridisation (ISH) for IgG4 and IgG. Twenty-six patients from the prospective cohort met the histological criteria for IgG4-RD (definite); 29 patients lacked one or more pathological features (borderline). Twenty biopsies (36%) lacked both storiform fibrosis and obliterative phlebitis, and nine (16%) lacked an increase in the number of IgG4-positive plasma cells. Ninety-three per cent of patients showed an IgG4/total IgG ratio of >40% (>30% by ISH). There were no differences in the incidence of multiorgan disease (P = 0.9), serum IgG4 levels (P = 0.6) and response to therapy between the definite and borderline groups. A strong correlation (Pearson 0.77) between the IHC and ISH platforms was noted with regard to the IgG4/total IgG ratio. CONCLUSION Patients with a presumptive diagnosis of IgG4-RD but lacking the characteristic pathological features of this disease appear to be clinically similar to those who meet the current pathological criteria. An elevated IgG4/total IgG ratio is the most sensitive pathological feature, and ISH provides a robust quantification platform. We recommend evaluating tumefactive lymphoplasmacytic infiltrates with an increased IgG4/IgG ratio, regardless of histological features, for IgG4-RD.
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Affiliation(s)
- Kshitij Arora
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Miguel Rivera
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - David T Ting
- Department of Medicine, Division of Hematology/Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Vikram Deshpande
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
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Quaglia A. Hepatocellular carcinoma: a review of diagnostic challenges for the pathologist. J Hepatocell Carcinoma 2018; 5:99-108. [PMID: 30519546 PMCID: PMC6235001 DOI: 10.2147/jhc.s159808] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Histopathologists retain a critical role in the diagnosis and management of hepatocellular carcinoma (HCC). HCC arises usually but not exclusively in a background of advanced-stage chronic liver disease. The histological diagnosis of HCC poses many challenges particularly when dealing with liver biopsy specimens due to the heterogeneity of HCC and the difficulty to confirm hepatocellular differentiation in some instances. Primary liver tumors should be considered as a continuum with typical hepatocellular and cholangiocarcinoma at the two ends and a whole range of tumors showing both hepatocellular and cholangiocellular differentiation with or without an associated progenitor/stem cell component in the middle. Characterization of combined (or mixed) hepatocellular-cholangiocarcinoma can be very challenging. In advanced-stage chronic liver disease, the main challenge for the histopathologist is still to differentiate between HCC and its precursors, although this is rarely critical in the clinical setting at present. HCC originating in non-cirrhotic livers needs to be differentiated from other primary and extrahepatic tumors and from hepatocellular adenoma, bearing in mind that progression to malignancy is more through a continuum that watertight histological categories.
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Affiliation(s)
- Alberto Quaglia
- Department of Cellular Pathology, Royal Free Hospital, London NW3 2QG, UK,
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Zambrano AR, Quesada JC, Torres AM, Escobar J, Prasad ML, Renjifo ME, Pabón LM. Diagnostically Challenging Case: Metastatic Hepatocellular Carcinoma With No Liver Lesion at Imaging. J Glob Oncol 2018; 4:1-5. [PMID: 30241223 PMCID: PMC6180752 DOI: 10.1200/jgo.17.00009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Angela R Zambrano
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Juan C Quesada
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Ana M Torres
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Juliana Escobar
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Manju L Prasad
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Martín E Renjifo
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
| | - Luz M Pabón
- Angela R. Zambrano, Juan C. Quesada, Ana M. Torres, Juliana Escobar, Martín E. Renjifo, and Luz M. Pabón, Fundación Valle del Lili, Cali, Colombia; and Manju L. Prasad, Yale University School of Medicine, New Haven, CT
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Chen ZH, Zhang XP, Cai XR, Xie SD, Liu MM, Lin JX, Ma XK, Chen J, Lin Q, Dong M, Wu XY, Wen JY, Xu RH. The Predictive Value of Albumin-to-Alkaline Phosphatase Ratio for Overall Survival of Hepatocellular Carcinoma Patients Treated with Trans-Catheter Arterial Chemoembolization Therapy. J Cancer 2018; 9:3467-3478. [PMID: 30310503 PMCID: PMC6171021 DOI: 10.7150/jca.26120] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2018] [Accepted: 08/15/2018] [Indexed: 02/06/2023] Open
Abstract
Background: We have previously reported the prognostic value of the albumin-to-alkaline phosphatase ratio (AAPR) for advanced hepatocellular carcinoma (HCC) patients who are not receiving any standard anticancer therapy. However, the prognostic value of the AAPR for HCC patients treated with trans-catheter arterial chemoembolization therapy (TACE) was not investigated. Methods: We retrospectively analysed 372 HCC patients treated with TACE (the training cohort) and applied receiver operating characteristic curves (ROC curves) to identify the best cut-off value for the AAPR in this cohort. Then, univariate analyses by the Kaplan-Meier method and multivariate analysis by a Cox proportional hazards regression model were conducted. Both comparisons of the ROC curves and the likelihood ratio test (LRT) were employed to evaluate the abilities of different factors in predicting the survival of patients in this cohort. Finally, the prognostic value of the AAPR was validated in two cohorts: one included 202 HCC patients treated with supportive care (validation cohort I), and the other included 82 HCC patients treated with TACE (validation cohort II). Results: We identified 0.439 as the best cut-off value of the AAPR by ROC curve analysis. An AAPR > 0.439 was significantly correlated with a lower frequency of Child-Pugh grade B, portal vein tumour thrombus (PVTT), T3-4 and lymph node metastasis (P < 0.05). The median overall survival (OS) of the patients with an AAPR > 0.439 was significantly longer than that of those with an AAPR ≤ 0.439 (58.4 m vs 17.8 m, respectively, P < 0.001). The AAPR was identified as an independent prognostic factor after univariate and multivariate analyses (HR = 0.636, P = 0.003). The independent prognostic value of the AAPR was also confirmed in validation cohorts I and II. Additionally, we substituted the AAPR for the Child-Pugh grade in the CLIP system and integrated the AAPR into the TNM system. We found that the area under the curve (AUC) of the AAPR-CLIP system was significantly larger than that of the CLIP and the TNM when predicting 3-month, 6-month, 1-year and 2-year survival (P < 0.05). There was no significant difference between the AUCs for the AAPR-CLIP and the AAPR-TNM. The LRT suggested that both AAPR-CLIP and AAPR-TNM had significantly larger χ2 values and smaller AIC values than that of their corresponding primary system (P < 0.05). Conclusions: The AAPR was an independent prognostic index for the HCC patients treated with TACE. Both AAPR-CLIP and AAPR-TNM outperformed their corresponding primary system in predicting OS in the current study.
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Affiliation(s)
- Zhan-Hong Chen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China.,Department of Medical Oncology of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, 510060, China
| | - Xiao-Ping Zhang
- Meihua Street Community Health Service Center, Yuexiu District Guangzhou, 510000, China
| | - Xiu-Rong Cai
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Si-Dong Xie
- Department of Radiology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Meng-Meng Liu
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Jin-Xiang Lin
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Xiao-Kun Ma
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Jie Chen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Qu Lin
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Min Dong
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Xiang-Yuan Wu
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Jing-Yun Wen
- Department of Medical Oncology and Guangdong Key Laboratory of Liver Disease, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China
| | - Rui-Hua Xu
- Department of Medical Oncology of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfengdong Road, Guangzhou, 510060, China
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Abstract
Fibrolamellar carcinoma is a rare primary hepatocellular malignancy arising in noncirrhotic livers of young individuals. Patients commonly present with a large solitary liver mass and nonspecific symptoms. Characteristic histologic features include large polygonal cells with oncocytic cytoplasm and prominent nucleoli separated into trabeculae and cords by dense parallel bands of collagen. Important differential diagnoses include classical hepatocellular carcinoma and intrahepatic cholangiocarcinoma, which may be distinguished by a judicious panel of immunohistochemical studies, including cytokeratin 7, CD68, and hepatocyte paraffin 1 (HepPar-1). In addition, fibrolamellar carcinomas are characterized by activation of protein kinase A. Prognosis of fibrolamellar carcinoma is similar to classical hepatocellular carcinoma occurring in the absence of liver cirrhosis and is strongly correlated with tumor resectability. Other treatment options include liver transplant, chemotherapy, and hepatic artery embolization. In this article, we review the clinical features, gross and microscopic pathology, molecular genetics, differential diagnosis, treatment, and prognosis of this rare and interesting tumor.
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Affiliation(s)
| | - Hui-Min Yang
- From the Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York. Dr Hui-Min Yang is currently located in the Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
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Ancillary tests in the diagnosis of liver and pancreatic neoplasms. Cancer Cytopathol 2018; 126 Suppl 8:672-690. [DOI: 10.1002/cncy.22009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2018] [Revised: 03/28/2018] [Accepted: 03/29/2018] [Indexed: 12/12/2022]
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Zhao CL, Hui Y, Wang LJ, Yang D, Yakirevich E, Mangray S, Huang CK, Lu S. Alanine-glyoxylate aminotransferase 1 (AGXT1) is a novel marker for hepatocellular carcinomas. Hum Pathol 2018; 80:76-81. [PMID: 29883780 DOI: 10.1016/j.humpath.2018.05.025] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Revised: 05/08/2018] [Accepted: 05/24/2018] [Indexed: 11/17/2022]
Abstract
Arginase-1 has been demonstrated as a marker for hepatocellular carcinoma (HCC) with higher sensitivity and specificity than HepPar-1 and glypican-3. However, its sensitivity is diminished in moderately and poorly differentiated HCCs. In the current study, we evaluated the utility of AGXT1 as a diagnostic marker. Immunostains for AGXT1 and arginase-1 were performed in tissue microarrays of 139 HCCs and 374 gastrointestinal and nongastrointestinal carcinomas. AGXT1 exhibited granular cytoplasmic immunoreactivity in contrast to the diffuse cytoplasmic staining characteristic of arginase-1 in nonneoplastic and neoplastic hepatocytes. Sensitivities of AGXT1 for all HCCs were 90.0% compared to 87.8% for arginase-1. A small number of tumors expressed only 1 of the 2 markers. Sensitivity increased to 92.1% when the presence of either marker was considered positive. Excepting 5 cases of cholangiocarcinoma, both AGXT1 and arginase-1 were negative in all non-HCC tumors with specificities of 98.7%. Our data support the consideration of AGXT1 as a novel hepatocellular marker with equally high specificity and slightly higher sensitivity as compared to arginase-1. AGXT1 may aid in diagnostic workup especially in conjunction with arginase-1 for HCCs that may otherwise defy conventional immunostaining patterns.
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Affiliation(s)
- Chaohui Lisa Zhao
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Yiang Hui
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Li Juan Wang
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Dongfang Yang
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Evgeny Yakirevich
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Shamlal Mangray
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903
| | - Chiung-Kuei Huang
- Liver Research Center, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903.
| | - Shaolei Lu
- Department of Pathology and Laboratory Medicine, Rhode Island Hospital and The Warren Alpert Medical School of Brown University, Providence, RI 02903.
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Lin F, Shi J, Wang HL, Ma XJ, Monroe R, Luo Y, Chen Z, Liu H. Detection of Albumin Expression by RNA In Situ Hybridization Is a Sensitive and Specific Method for Identification of Hepatocellular Carcinomas and Intrahepatic Cholangiocarcinomas. Am J Clin Pathol 2018; 150:58-64. [PMID: 29746696 DOI: 10.1093/ajcp/aqy030] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Inconsistent data on detection of albumin expression by ribonucleic acid (RNA) in situ hybridization have been reported. We investigated the utility of RNAscope (Advanced Cell Diagnostics, Hayward, CA) in detection of albumin in hepatocellular carcinomas (HCCs), intrahepatic cholangiocarcinomas (ICCs), and carcinomas from various organs using manual and automated staining. METHODS RNAscope for albumin detection was performed on 482 cases on tissue microarray sections and on 22 cases of ICC, including 14 surgical resection and eight core biopsy specimens. RESULTS Thirty-six of 37 (97%) HCCs had detectable mRNA, whereas all non-HCC and non-ICC cases, except one lung adenocarcinoma, were negative for albumin. Fourteen of 22 ICCs (64%) were positive for albumin. CONCLUSIONS RNAscope for albumin is highly sensitive and specific for identifying HCCs and is highly specific and moderately sensitive for detection of ICCs; however, rare carcinomas (non-HCC, non-ICC, and those with no hepatoid histomorphology) can also have aberrant expression of albumin.
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Affiliation(s)
- Fan Lin
- Geisinger Medical Center, Danville, PA
| | | | - Hanlin L Wang
- Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles
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Koehne de Gonzalez A, Lagana SM. Update on Ancillary Testing in the Evaluation of High-Grade Liver Tumors. Surg Pathol Clin 2018; 11:367-375. [PMID: 29751880 DOI: 10.1016/j.path.2018.02.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Tissue diagnosis is the gold standard for mass lesions of the liver, but needle core biopsies may sometimes prove challenging. Presented here is a review of a panel of immunohistochemical stains, including hepatocyte in paraffin 1, arginase-1, polyclonal carcinoembryonic antigen, CD10, bile salt export pump, glypican-3, as well as in situ hybridization for albumin RNA, to establish hepatocellular origin in cases in which hepatocellular carcinoma is suspected but the sample is limited or the morphology is challenging, as it may be with cases of scirrhous, fibrolamellar carcinoma, intrahepatic cholangiocarcinoma, and combined hepatocellular-cholangiocarcinoma.
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Affiliation(s)
- Anne Koehne de Gonzalez
- Department of Pathology and Cell Biology, Columbia University, 622 W 168th Street, Vanderbilt Clinic 14-209, New York, NY 10032, USA
| | - Stephen M Lagana
- Department of Pathology and Cell Biology, Columbia University, 622 W 168th Street, Vanderbilt Clinic 14-209, New York, NY 10032, USA.
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Ferrell LD, Kakar S, Terracciano LM, Wee A. Tumours and Tumour-like Lesions of the Liver. MACSWEEN'S PATHOLOGY OF THE LIVER 2018:780-879. [DOI: 10.1016/b978-0-7020-6697-9.00013-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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A subset of well-differentiated hepatocellular carcinomas are Arginase-1 negative. Hum Pathol 2017; 69:90-95. [DOI: 10.1016/j.humpath.2017.09.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Revised: 09/13/2017] [Accepted: 09/22/2017] [Indexed: 12/25/2022]
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Wang HL, Kim CJ, Koo J, Zhou W, Choi EK, Arcega R, Chen ZE, Wang H, Zhang L, Lin F. Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas. Arch Pathol Lab Med 2017; 141:1155-1180. [PMID: 28854347 DOI: 10.5858/arpa.2016-0489-ra] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
CONTEXT - Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. OBJECTIVES - To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. DATA SOURCES - Data sources include literature review, authors' research data, and personal practice experience. CONCLUSIONS - Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.
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