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Oh W, Min J, Kim BH. Comprehensive Approach to Cytomorphology in Liquid-Based Bile Duct Brush Cytology: Integrating Cell Blocks and Histology. Diagn Cytopathol 2025; 53:204-214. [PMID: 39887597 DOI: 10.1002/dc.25443] [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] [Received: 10/01/2024] [Revised: 01/08/2025] [Accepted: 01/15/2025] [Indexed: 02/01/2025]
Abstract
Bile duct brush cytology is a widely used and essential method for evaluating biliary tract lesions, although it remains challenging for pathologists. Liquid-based preparations provide a better vision of morphology and enable the preparation of cell blocks, thereby enhancing reliability. However, the establishment of reproducible interpretation criteria and utilization of cell blocks remain limited. This study aimed to investigate the morphological features of liquid-based cytology using objective and reproducible criteria, incorporating histological findings to identify diagnostic features. In total, 151 cases were selected and 42 morphologic criteria were evaluated within representative clusters. Notably, 14 features, including conventional cytologic features, significantly differed between the benign and malignant groups. Malignant cell clusters were more likely to be irregularly shaped and have larger nuclear sizes, increased nuclear pleomorphism, a non-euchromatic chromatin pattern, and a higher nucleus-to-cytoplasm (N/C) ratio. Multinucleation and nuclear molding were observed exclusively in malignant cases. The presence of inflammatory cells did not differ significantly between benign and malignant cases. An increased N/C ratio was observed in the cell blocks and the architectural information aided in diagnosis. The application of cell blocks may be beneficial, emphasizing the significance of nuclear pleomorphism. We also categorized features by analyzing the sensitivity, specificity, and importance of various features. In summary, our study reaffirms the importance of conventional cytomorphologic features in liquid-based preparations of bile duct cytology and suggests a diagnostic approach with more objective morphologic criteria, highlighting the utility of cell blocks.
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Affiliation(s)
- Wookjin Oh
- Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Jaeyong Min
- Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
| | - Baek-Hui Kim
- Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea
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Selvaraj S, Dharmalingam P, Alashetty S, Patil A. Reproducibility assessment of WHO reporting system for pancreaticobiliary cytopathology: A single institution experience. Diagn Cytopathol 2024; 52:617-626. [PMID: 38860686 DOI: 10.1002/dc.25367] [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] [Received: 02/29/2024] [Revised: 05/28/2024] [Accepted: 05/31/2024] [Indexed: 06/12/2024]
Abstract
BACKGROUND The World Health Organization (WHO) reporting system for pancreaticobiliary cytopathology was released to internationalize the reporting, assisting in correct diagnosis and patient treatment with significant revisions from the previous Papanicolaou Society of Cytopathology (PSC) system. The "neoplastic: benign" and "neoplastic: other" categories have mostly been superseded by two new ones: "pancreatic neoplasia-low-grade" (PaN-low) and "pancreatic neoplasia-high-grade" (PaN-high), which classify intermediate neoplastic lesions based on cytological atypia. We aim to assess the reproducibility and risk of malignancy (ROM) for reporting pancreaticobiliary cytopathology by the WHO system in comparison with the PSC system. MATERIALS AND METHODS A retrospective study by reviewing archival slides sent for pancreaticobiliary cytological evaluation from June 2021 to June 2023, by two pathologists blinded to each other's findings. Absolute ROM was determined by histopathology/cell block study/clinical follow-up (minimum 6 months)/overtly malignant imaging/metastasis. RESULTS A total of 332 cases from 329 patients met the inclusion criteria, comprising pancreatic, gallbladder, and biliary lesions. The median patient age was 54 years (range, 14-86 years). The overall sensitivity of the test is 74.9% specificity is 93.2%, positive predictive value of 96.8%, negative predictive value of 57.6%, and a diagnostic accuracy of 81.8%. The absolute ROM for each site in all categories was comparable with that of the published data from the WHO system. CONCLUSION Our study highlights the reliability of the WHO system for guiding clinical decision-making and patient management in the context of pancreaticobiliary. However, continual efforts among pathologists are essential to maintain consistent accuracy in cytological interpretations.
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Affiliation(s)
- Sivaranjani Selvaraj
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Priya Dharmalingam
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Soumya Alashetty
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
| | - Akkamahadevi Patil
- Department of Pathology, Kidwai Memorial Institute of Oncology, Bengaluru, Karnataka, India
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Wang M, Lozano MD, Cai G. The World Health Organization System for Reporting Pancreaticobiliary Cytopathology: Standardized Categories and Practical Approaches to Pancreatic Lesions. JOURNAL OF CLINICAL AND TRANSLATIONAL PATHOLOGY 2024; 4:122-135. [PMID: 40191142 PMCID: PMC11969574 DOI: 10.14218/jctp.2024.00034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 04/09/2025]
Abstract
The World Health Organization System for Reporting Pancreaticobiliary Cytopathology introduces a seven-tier category system to standardize terminology and nomenclature. This system includes the following categories: Insufficient/non-diagnostic, benign/negative for malignancy, atypia, pancreaticobiliary neoplasm low-risk/grade, pancreaticobiliary neoplasm high-risk/grade, suspicious for malignancy, and malignant categories. Adopting a standardized reporting scheme facilitates consistent diagnostic criteria among pathologists, thereby reducing report variability and enhancing communication with the clinical team for optimal patient management. The report also highlights the role of critical ancillary tests in improving diagnostic accuracy for pancreatic lesions and discusses practical approaches to managing solid and cystic pancreatic lesions.
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Affiliation(s)
- Minhua Wang
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
| | - Maria D. Lozano
- Department of Pathology, University of Navarra, Pamplona, Navarra, Spain
| | - Guoping Cai
- Department of Pathology, Yale School of Medicine, New Haven, CT, USA
- Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA
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Wang X, Zhang X, Hui P, Cai G. Improving diagnostic yield of pancreatic serous cystadenoma with cyst fluid ancillary testing, adjunct immunohistochemistry, and additional fine-needle biopsy sampling. Cancer Cytopathol 2024; 132:425-434. [PMID: 38450993 DOI: 10.1002/cncy.22808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/24/2024] [Accepted: 02/13/2024] [Indexed: 03/08/2024]
Abstract
BACKGROUND Fine-needle aspiration (FNA) diagnosis of pancreatic serous cystadenoma (SCA) remains challenging. This retrospective study aimed to evaluate the roles of cyst fluid ancillary testing and combined fine-needle biopsy (FNB) in improving the diagnostic yield. METHODS The authors retrospectively reviewed cytology cases that were histologically confirmed SCAs. Clinical features and FNA cyst fluid biochemical and molecular analysis results along FNB findings were reviewed. RESULTS The study cohort included 31 cases from 13 male and 18 female patients with a mean age of 65. The original cytologic diagnoses were nondiagnostic (n = 6, 19%), negative for malignant cells/cyst contents (n = 7, 23%), atypical cells (n = 3, 10%), nonmucinous cyst (n = 11, 35%), and serous cystadenoma (n = 4, 13%). Cyst fluid carcinoembryonic antigen (CEA) analysis was performed in 17 cases, all of which showed a low CEA level (<192 ng/mL). All 14 cases with molecular testing showed a wild-type KRAS. Inhibin immunohistochemistry was retrospectively performed on the FNA cell blocks, inhibin was positive in six of seven cases tested. In 15 cases with concurrent FNA and FNB biopsies, the diagnosis of SCA was seen in only one FNA case (7%) but 13 FNB cases (87%). CONCLUSIONS This study suggests that FNA diagnosis of SCA remains challenging even with ancillary testing including cyst fluid CEA level and KRAS mutation analysis. Adjunct inhibin immunostaining may help improve the cytologic diagnosis of selective SCA cases. FNB appears superior to FNA for a definite diagnosis of SCA.
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Affiliation(s)
- Xi Wang
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Xuchen Zhang
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
| | - Guoping Cai
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA
- Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut, USA
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Taheri N, Graham RP. How Molecular Discoveries Have Changed Liver Tumor Pathology: A Brief Review. Arch Pathol Lab Med 2024; 148:e96-e102. [PMID: 37639429 DOI: 10.5858/arpa.2023-0099-ra] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/21/2023] [Indexed: 08/31/2023]
Abstract
CONTEXT Recent molecular discoveries have led to improved understanding of tumor biology and the development of new diagnostic assays. OBJECTIVE To review primarily 3 examples of liver tumors and to briefly illustrate how recent molecular discoveries have altered clinical liver pathology practice. DATA SOURCES First, we will discuss fibrolamellar carcinoma, which will be the main focus of discussion, as an example for new diagnostic tests that have been developed as a result of molecular discoveries. Additional information on the role of molecular diagnostics in hepatocellular adenoma and hepatocellular carcinoma will be provided. Second, we will use the example of epithelioid hemangioendothelioma as an example of how new diagnostic tools, based on molecular discoveries, may support improved prognostication. Finally, we will use the example of intrahepatic cholangiocarcinoma as an example of a liver tumor where new molecular discoveries have identified tractable therapeutic targets and led to new effective therapies. This portion of the manuscript will also include a description of the anatomic and molecular differences between intrahepatic, hilar, and extrahepatic cholangiocarcinoma. CONCLUSIONS Fueled by molecular discoveries, new and better diagnostic tests and therapeutic targets have improved clinical care in patients affected by liver tumors.
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MESH Headings
- Humans
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- Liver Neoplasms/diagnosis
- Cholangiocarcinoma/genetics
- Cholangiocarcinoma/pathology
- Cholangiocarcinoma/diagnosis
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/diagnosis
- Hemangioendothelioma, Epithelioid/genetics
- Hemangioendothelioma, Epithelioid/pathology
- Hemangioendothelioma, Epithelioid/diagnosis
- Adenoma, Liver Cell/pathology
- Adenoma, Liver Cell/genetics
- Adenoma, Liver Cell/diagnosis
- Bile Duct Neoplasms/genetics
- Bile Duct Neoplasms/pathology
- Bile Duct Neoplasms/diagnosis
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Molecular Diagnostic Techniques
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Affiliation(s)
- Negar Taheri
- From the Enteric Neuroscience Program and Department of Physiology and Biomedical Engineering (Taheri)
- the Gastroenterology Research Unit, Mayo Clinic College of Medicine, Rochester, Minnesota(Taheri)
| | - Rondell P Graham
- the Divisions of Anatomic Pathology, , Mayo Clinic, Rochester, Minnesota(Graham)
- Laboratory Genetics and Genomics, Mayo Clinic, Rochester, Minnesota(Graham)
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Verma P, Goyal S, Tyagi R, Ghuman M, Mahajan R, Selhi AK, Kaur H, Selhi PK. Reporting Pancreatic FNAC using the Papanicolaou System: Still a Diagnostic Challenge. J Cytol 2024; 41:123-130. [PMID: 38779600 PMCID: PMC11108040 DOI: 10.4103/joc.joc_90_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 02/06/2024] [Accepted: 03/28/2024] [Indexed: 05/25/2024] Open
Abstract
Introduction The Papanicolaou Society of Cytopathology System for reporting Pancreaticobiliary Cytology (PSCPC) is a reliable method to classify pancreatic fine needle aspiration cytology (FNAC) smears. However, it is not without practical problems which can diminish the diagnostic accuracy of the cytological diagnosis. Aims and Objectives To determine the diagnostic pitfalls while reporting cytomorphology of pancreatic lesions according to PSCPC on correlating FNAC findings with histopathology. Materials and Methods Retrospective analysis of pancreatic FNAC smears received in the Department of Pathology of our tertiary care institute over a period of 2 years was done. The cytological diagnoses were classified according to the Papanicolaou Society of Cytopathology system of reporting pancreaticobiliary cytology and correlated with histopathology. The reasons of cyto-histological discordance were analyzed. Results Out of 50 cases in which both FNAC and biopsy of pancreatic lesions were done, 34 cases were positive/malignant (Category VI), eight cases were suspicious for malignancy (Category V), three cases were neoplastic (Category IV), two cases were atypical (Category III), two cases were negative for malignancy (Category II), and one case was non-diagnostic (Category I). Out of 50 cases, histopathology was non-diagnostic due to inadequate material in six cases. The cytological diagnoses were compared with histopathology in the remaining 44 cases. Categories III, IV V, and VI were considered as positive for neoplastic pathology. The sensitivity of FNAC to predict neoplastic pathology was 97.5%, while the specificity was 25%. The positive predictive value was 92.9%. Two cases reported as atypical (Category III) turned out to be adenocarcinoma on histopathology. One case reported as neuroendocrine tumor and two cases reported as adenocarcinoma on cytology displayed features of chronic pancreatitis on histology. One case reported as neoplastic mucinous cyst (Category IV) turned out to be adenocarcinoma on histology (limited concordance). Conclusion The cytopathologist needs to be wary of the potential pitfalls to improve the diagnostic accuracy of FNACs.
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Affiliation(s)
- Parul Verma
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Saloni Goyal
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ruchita Tyagi
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Mehar Ghuman
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Arshneet Kaur Selhi
- Department of Pathology, Lady Hardinge Medical College, Connaught Place, New Delhi, India
| | - Harpreet Kaur
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
| | - Pavneet Kaur Selhi
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
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Wood LD, Adsay NV, Basturk O, Brosens LAA, Fukushima N, Hong SM, Kim SJ, Lee JW, Luchini C, Noë M, Pitman MB, Scarpa A, Singhi AD, Tanaka M, Furukawa T. Systematic review of challenging issues in pathology of intraductal papillary mucinous neoplasms. Pancreatology 2023; 23:878-891. [PMID: 37604731 DOI: 10.1016/j.pan.2023.08.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 08/03/2023] [Accepted: 08/08/2023] [Indexed: 08/23/2023]
Abstract
BACKGROUND Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are frequently treated with surgical resection, and pathological examination of the pancreatectomy specimen is a key component of the clinical care of IPMN patients. METHODS Systematic literature reviews were conducted around eight topics of clinical relevance in the examination of pathological specimens in patients undergoing resection of IPMN. RESULTS This review provides updated perspectives on morphological subtyping of IPMNs, classification of intraductal oncocytic papillary neoplasms, nomenclature for high-grade dysplasia, assessment of T stage, distinction of carcinoma associated or concomitant with IPMN, role of molecular assessment of IPMN tissue, role of intraoperative assessment by frozen section, and preoperative evaluation of cyst fluid cytology. CONCLUSIONS This analysis provides the foundation for data-driven approaches to several challenging issues in the pathology of IPMNs.
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Affiliation(s)
- Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
| | - N Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey
| | - Olca Basturk
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lodewijk A A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Noriyoshi Fukushima
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Sung-Joo Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae W Lee
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy; ARC-Net Research Center, University of Verona, 37134, Verona, Italy
| | - Michaël Noë
- Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Aldo Scarpa
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, 37134, Verona, Italy; ARC-Net Research Center, University of Verona, 37134, Verona, Italy
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Mariko Tanaka
- Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
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Layfield LJ, Zhang T, Esebua M. Molecular features of pancreaticobiliary neoplasms: Implications for diagnosis, prognostication, and therapy selection. Diagn Cytopathol 2023; 51:5-11. [PMID: 35751521 DOI: 10.1002/dc.25005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 06/09/2022] [Indexed: 01/01/2023]
Abstract
BACKGROUND Molecular diagnostics has impacted the diagnosis, prediction of prognosis, and selection of targeted therapy for many tumor types. While pulmonary adenocarcinomas and melanomas are among the neoplasms most associated with molecular diagnostics and targeted therapy, malignancies of the pancreaticobiliary system have also been impacted by precision medicine. METHODS We undertook an electronic search using PubMed and Embase to review the published literature to determine what forms of molecular testing, mutations and oncogenetic pathways are associated with neoplasms of the pancreaticobiliary system. Keywords utilized were pancreas, bile duct, mutations, ERCP, FNA, KRAS, SMAD4, TP53, next-generation sequencing, serous cystadenoma, pancreatic ductal adenocarcinoma, intraductal papillary mucinous neoplasm, cystic mucinous neoplasm, solid pseudo-papillary neoplasm. RESULTS A search between 1999 and 2022 yielded 6874 manuscripts. Screening of these yielded 302 more focused manuscripts of which 55 were used for the study. Ductal adenocarcinoma of the pancreas is associated with a progression of mutations beginning wit KRAS mutations and ending with a set of mutations in the TP53, SMAD4, and DPC4 genes. Similar mutations are found in neoplastic mucinous cysts. Specific mutations characterize serous cystadenomas, solid, and pseudo papillary neoplasms and adenocarcinomas of the bile ducts. CONCLUSIONS Mutational analysis of cytologic specimens obtained by fine-needle aspiration, and duct brushings and washings are helpful in the diagnosis of pancreaticobiliary neoplasms and may supply prognostic information.
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Affiliation(s)
- Lester J Layfield
- The Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA
| | - Tao Zhang
- The Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA
| | - Magda Esebua
- The Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA
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Approach to FNA of Pancreatic Cysts. Adv Anat Pathol 2022; 29:349-357. [DOI: 10.1097/pap.0000000000000378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Gocun PU, Simsek B, Ekinci O, Ekmen N, Arhan M, Karakan T, Ibis M, Cindoruk M. Risk of Malignancy Using the Diagnostic Categories Proposed by the World Health Organization International System for Reporting Pancreaticobiliary Cytopathology. Acta Cytol 2022; 66:475-485. [PMID: 35732161 PMCID: PMC9808633 DOI: 10.1159/000525276] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/22/2022] [Indexed: 01/07/2023]
Abstract
BACKGROUND The World Health Organization (WHO) proposed an updated reporting system for pancreaticobiliary cytology, which moves low-grade malignancies to "positive for malignancy" group and serous cystadenoma to "negative for malignancy" group. The WHO system also created two new categories, namely, pancreatic neoplasia-low grade (PaN-Low) and pancreatic neoplasia-high grade (PaN-High), which includes neoplastic mucinous cysts and stratifies them according to their cytologic atypia. The risk of malignancy (ROM) of the new categories of the WHO system needs to be defined. METHODS Cytologic slides of all patients, who underwent endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy at our institution from January 2010 to December 2021 and had a histopathological or clinical follow-up of at least 6 months, were reviewed and reclassified under the Papanicolaou Society of Cytopathology (PSC) and WHO reporting systems. The absolute ROM was calculated for each category of both reporting systems. RESULTS A total of 420 EUS-FNA samples from 410 patients were reviewed and reclassified. The absolute ROM for the proposed WHO system was 35% for "nondiagnostic," 1.0% for "negative for malignancy," 69.0% for "atypical," 11% for "PaN-Low," 100% for "PaN-High," 91% for "suspicious for malignancy," and 100% for "malignant." Comparatively, the absolute ROM under the PSC reporting system was 34% for "nondiagnostic," 1.0% for negative (for malignancy), 50.0% for "atypical," 0.0% for "neoplastic: benign," 16% for "neoplastic: other," 88% for "suspicious for malignancy," and 100% for "positive or malignant." CONCLUSION The proposed WHO international reporting system has advantages regarding risk stratification improvement and case management.
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Affiliation(s)
- Pınar Uyar Gocun
- Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Berkay Simsek
- Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Ozgur Ekinci
- Department of Pathology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Nergis Ekmen
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Mehmet Arhan
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Tarkan Karakan
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Mehmet Ibis
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
| | - Mehmet Cindoruk
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Gazi University, Ankara, Turkey
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Sun T, Zuo T, Hui P, Cai G. Significance of KRAS mutation testing in biliary brushing cytology specimens: A 10-year retrospective review. Cancer Cytopathol 2022; 130:558-565. [PMID: 35417072 DOI: 10.1002/cncy.22579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 03/17/2022] [Accepted: 03/18/2022] [Indexed: 11/09/2022]
Abstract
BACKGROUND Biliary strictures can be caused by benign and malignant conditions. A biliary duct brushing diagnosis can be challenging because of low cellularity and overlapping morphology among different entities, leading to a variable reported sensitivity. This study aimed to assess the value of KRAS mutation testing in adding cytological diagnosis of biliary duct brushings. METHODS With institutional review board approval, biliary duct brushing cytology specimens were collected from 269 patients with extrahepatic biliary stenosis between August 2011 and July 2021. The results of cytology and KRAS mutational analyses were evaluated in view of corresponding cytology examination and histopathological/clinical follow-up. RESULTS KRAS mutations were identified in 50 of 269 biliary stricture brushing cases (19%). Among the cases with available follow-up, 72% (34 of 47) of biliary brushings had confirmed malignancy when there were KRAS mutations. The overall specificity and sensitivity of KRAS mutation testing was 92% and 36%, respectively. KRAS mutation was significantly more enriched in pancreatic duct adenocarcinoma than in cholangiocarcinoma (66% vs 5%, P < .001). The absolute risk of malignancy was 3%, 28%, and 71%, respectively, in negative, atypical, and suspicious cytological diagnostic categories and the risks increased to 14%, 68%, and 95% in corresponding categories with KRAS mutation. CONCLUSIONS Our results suggested that KRAS mutational analysis can be considered supplementary to cytology diagnosis of biliary duct brushing for patients with extrahepatic biliary stenosis in clinical practice.
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Affiliation(s)
- Tong Sun
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
| | - Tao Zuo
- Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts
| | - Pei Hui
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut
| | - Guoping Cai
- Department of Pathology, Yale University School of Medicine, New Haven, Connecticut.,Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut
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Dinarvand P, Wang WL, Roy-Chowdhuri S. Utility of SOX11 for the diagnosis of solid pseudopapillary neoplasm of the pancreas on cytological preparations. Cytopathology 2022; 33:216-221. [PMID: 34816516 PMCID: PMC8813899 DOI: 10.1111/cyt.13080] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 11/09/2021] [Accepted: 11/19/2021] [Indexed: 11/30/2022]
Abstract
INTRODUCTION The diagnosis of solid pseudopapillary neoplasm (SPN) on fine needle aspiration specimens can be challenging because of morphological overlap with other pancreatic neoplasms, including pancreatic neuroendocrine tumour (PanNET). SRY-related high-mobility group box 11 (SOX11) is a recently described sensitive and specific marker for SPN diagnosis. However, SOX11 immunocytochemistry on cytological smears has not been reported. We evaluated the utility of SOX11 for diagnosis of SPN on cytological preparations. METHODS SOX11 immunocytochemistry was performed on Papanicolaou-stained smears and/or corresponding cell blocks from aspirates of 7 SPN and 10 PanNET cases identified between 2005 and 2020. Findings were compared with those for beta-catenin, a frequently used diagnostic marker for SPN. RESULTS Six smears and 6 cell blocks from SPN cases and 8 smears and 10 cell blocks from PanNET cases were available for immunostaining. For SPN, nuclear staining for SOX11 was seen in 6 of 6 (100%) smears and 5 of 6 (83%) cell blocks, with equivocal staining in 1 cell block. In contrast, 7 of 8 (88%) smears and 9 of 10 (90%) cell blocks were negative for SOX11 for PanNet, with equivocal staining seen in 1 case. Beta-catenin immunocytochemistry showed nuclear staining in 6 of 7 (86%) SPN cases and no staining in all 10 (100%) PanNET cases. CONCLUSIONS SOX11 detected by immunocytochemistry can serve as a useful diagnostic marker for SPN, in addition to beta catenin, and can be performed on cytological smears in cases without a cell block preparation.
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Affiliation(s)
- Peyman Dinarvand
- Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Wei-Lien Wang
- Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sinchita Roy-Chowdhuri
- Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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13
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Hirao M, Hosui A, Mimura A, Ohnishi K, Tanimoto T, Okahara T, Sueyoshi Y, Goto T, Yamada T, Hiramatsu N. Significance of in vitro photodynamic cytodiagnosis with 5-aminolevulinic acid in biliary brush cytology for malignant biliary stricture. Photodiagnosis Photodyn Ther 2022; 38:102756. [PMID: 35150900 DOI: 10.1016/j.pdpdt.2022.102756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/08/2022] [Accepted: 02/08/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND For the early diagnosis of malignant biliary stricture due to biliary-pancreatic carcinoma, conventional biliary brush cytology with endoscopic retrograde cholangiopancreatography (ERCP; the conventional method) is not sensitive enough. METHODS Two hundred nine patients with biliary stricture who were admitted between September 2015 and June 2020 were enrolled in this study. Biliary brush cytology was performed on all patients. Samples were diagnosed independently by an expert pathologist and medical doctor with conventional cytology and photodynamic diagnosis (PDD) with 5-aminolevulinic acid. RESULTS The definitive diagnoses were 49 benign and 160 malignant diseases. The conventional method had a sensitivity of 77.5% (124/160) and specificity of 100% (49/49). The PDD method had a sensitivity of 77.5% (124/160) and specificity of 67.3% (33/49). The conventional method identified 36 malignant diseases as false negatives, while the PDD method enabled successful diagnoses of malignant diseases in 19 of these 36 patients. When PDD was combined with the conventional method, the sensitivity significantly increased to 89.4% (143/160, P=0.006), and for biliary tract diseases only, the sensitivity increased to 95.6% (88/92, P=0.001). CONCLUSIONS Malignant biliary stricture can be diagnosed effectively and safely with the in vitro PDD method. The sensitivity could be further increased by combining PDD with the conventional method.
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Affiliation(s)
- Motohiro Hirao
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka.
| | - Atsushi Hosui
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Akihiro Mimura
- Department of Pathology, Osaka Rosai Hospital, Sakai, Osaka
| | - Kohsaku Ohnishi
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Takashi Tanimoto
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Toru Okahara
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Yuka Sueyoshi
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Takayoshi Goto
- Department of Pathology, Osaka Rosai Hospital, Sakai, Osaka
| | - Takuya Yamada
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
| | - Naoki Hiramatsu
- Department of Gastroenterology and Hepatology, Osaka Rosai Hospital, Sakai, Osaka
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14
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Nikas IP, Proctor T, Seide S, Chatziioannou SS, Reynolds JP, Ntourakis D. Diagnostic Performance of Pancreatic Cytology with the Papanicolaou Society of Cytopathology System: A Systematic Review, before Shifting into the Upcoming WHO International System. Int J Mol Sci 2022; 23:1650. [PMID: 35163571 PMCID: PMC8835850 DOI: 10.3390/ijms23031650] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2021] [Revised: 01/19/2022] [Accepted: 01/28/2022] [Indexed: 02/01/2023] Open
Abstract
The Papanicolaou Society of Cytopathology (PSC) reporting system classifies pancreatobiliary samples into six categories (I-VI), providing guidance for personalized management. As the World Health Organization (WHO) has been preparing an updated reporting system for pancreatobiliary cytopathology, this systematic review aimed to evaluate the risk of malignancy (ROM) of each PSC category, also the sensitivity and specificity of pancreatic FNA cytology using the current PSC system. Five databases were investigated with a predefined search algorithm. Inclusion and exclusion criteria were applied to select the eligible studies for subsequent data extraction. A study quality assessment was also performed. Eight studies were included in the qualitative analysis. The ROM of the PSC categories I, II, III, IV, V, VI were in the ranges of 8-50%, 0-40%, 28-100%, 0-31%, 82-100%, and 97-100%, respectively. Notably, the ROM IVB ("neoplastic-benign") subcategory showed a 0% ROM. Four of the included studies reported separately the ROMs for the IVO subcategory ("neoplastic-other"; its overall ROM ranged from 0 to 34%) with low (LGA) and high-grade atypia (HGA). ROM for LGA ranged from 4.3 to 19%, whereas ROM for HGA from 64 to 95.2%. When the subcategory IVO with HGA was considered as cytologically positive, together with the categories V and VI, there was a higher sensitivity of pancreatic cytology, at minimal expense of the specificity. Evidence suggests the proposed WHO international system changes-shifting the IVB entities into the "benign/negative for malignancy" category and establishing two new categories, the "pancreatic neoplasm, low-risk/grade" and "pancreatic neoplasm, high-risk/grade"-could stratify pancreatic neoplasms more effectively than the current PSC system.
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Affiliation(s)
- Ilias P. Nikas
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (S.S.C.); (D.N.)
| | - Tanja Proctor
- Institute of Medical Biometry, University of Heidelberg, 69120 Heidelberg, Germany; (T.P.); (S.S.)
| | - Svenja Seide
- Institute of Medical Biometry, University of Heidelberg, 69120 Heidelberg, Germany; (T.P.); (S.S.)
| | | | - Jordan P. Reynolds
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL 32256, USA;
| | - Dimitrios Ntourakis
- School of Medicine, European University Cyprus, Nicosia 2404, Cyprus; (S.S.C.); (D.N.)
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15
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Lymphoid Enhancer Binding Factor 1 (LEF1) and Paired Box Gene 8 (PAX8): A Limited Immunohistochemistry Panel to Distinguish Solid Pseudopapillary Neoplasms and Pancreatic Neuroendocrine Tumors. Appl Immunohistochem Mol Morphol 2021; 28:776-780. [PMID: 32723981 DOI: 10.1097/pai.0000000000000830] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PanNETs) are distinctive entities. However, due to overlapping morphologies, distinguishing them remains a diagnostic challenge. Our study investigates the utility of immunohistochemistry for nuclear lymphoid enhancer binding factor 1 (LEF1) and paired box gene 8 (PAX8) in differentiating these 2 entities. LEF1 and PAX8 immunohistochemistry were performed on fine-needle aspiration cell blocks and surgical resection specimens diagnosed as SPN or PanNET at our institution from January 2007 to August 2016. Eight SPN and 25 PanNET cell blocks and 17 SPN and 34 PanNET surgical resection specimens were examined. On cell blocks, positive staining for LEF1 had high frequency, sensitivity, and specificity for SPN (88%, 88%, and 88%) as did positive staining for PAX8 for PanNET (76%, 76%, and 75%). The findings on surgical resection specimens were consistent with those from cell blocks (LEF1+ in SPN: 100%, 100%, and 97%; PAX8+ in PanNET: 59%, 59%, and 100%). A combined LEF1+/PAX8- phenotype showed high sensitivity and specificity for SPN (cell block: 63% and 100%; surgical specimen: 100% and 98%) as did a LEF1-/PAX8+ phenotype for PanNET (cell block: 64% and 100%; surgical specimen: 59% and 100%). SPN and PanNET exhibit opposite immunophenotypic profiles with LEF1+/PAX8- in SPN and LEF1-/PAX8+ in PanNET. The combination of these 2 stains provides an effective means of distinguishing these 2 entities.
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16
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HooKim K, Reid MD. Atypical cells in fine needle aspiration biopsies of pancreas: Causes, work-up, and recommendations for management. Diagn Cytopathol 2021; 50:196-207. [PMID: 34378874 DOI: 10.1002/dc.24848] [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] [Received: 07/27/2021] [Accepted: 07/29/2021] [Indexed: 12/22/2022]
Abstract
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a sensitive and specific method for diagnosing cancer in solid pancreatic masses. However, some cases receive indeterminate atypical diagnoses, which creates management dilemmas. In the 2014 Papanicolaou Society of Cytopathology (PSC) standardized guidelines for pancreatobiliary cytology, specimens in the "Atypical" category show a spectrum of architectural and/or cellular changes beyond normal or reactive, but, quantitatively or qualitatively, insufficient for classification as neoplastic (benign/other), suspicious or positive for malignancy. Implementation of the PSC system decreased atypical diagnoses, particularly for cystic lesions, and redistributed many cases into benign and neoplastic categories. Because no set cytologic criteria exist for the "Atypical" category there is wide variability in its use, and its frequency ranges from 0%-16% (mean 6%). It consists of a heterogeneous mix of cases that occur because of preanalytic, lesion-specific (low cellularity, necrosis, cystic, reactive and premalignant changes), to pathologist-dependent factors (experience, expertise, training and institutional case volume). Outcomes of atypical diagnoses in solid pancreatic masses range from benign to premalignant and malignant and include reactive atypia in pancreatitis, well differentiated adenocarcinoma, and non-ductal malignancies. The associated risk of malignancy (ROM) ranges from 28%-100%, with an overall intermediate ROM in large-scale studies. Cytopathologists and institutions should monitor and keep their personal and/or laboratory's atypical rates low by judiciously using rapid onsite evaluation, ancillary studies, consensus or expert review, as well as correlation with clinical and radiologic findings. Early repeat EUS-FNA is indicated for unresolved cases.
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Affiliation(s)
- Kim HooKim
- Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
| | - Michelle D Reid
- Department of Pathology, Emory University Hospital, Atlanta, Georgia, USA
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17
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Visani M, Acquaviva G, De Leo A, Sanza V, Merlo L, Maloberti T, Brandes AA, Franceschi E, Di Battista M, Masetti M, Jovine E, Fiorino S, Pession A, Tallini G, de Biase D. Molecular alterations in pancreatic tumors. World J Gastroenterol 2021; 27:2710-2726. [PMID: 34135550 PMCID: PMC8173386 DOI: 10.3748/wjg.v27.i21.2710] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/25/2021] [Accepted: 04/14/2021] [Indexed: 02/06/2023] Open
Abstract
Genetic alterations in pancreatic tumors can usually be classified in: (1) Mutational activation of oncogenes; (2) Inactivation of tumor suppressor genes; and (3) Inactivation of genome maintenance genes controlling the repair of DNA damage. Endoscopic ultrasound-guided fine-needle aspiration has improved pre-operative diagnosis, but the management of patients with a pancreatic lesion is still challenging. Molecular testing could help mainly in solving these "inconclusive" specimens. The introduction of multi-gene analysis approaches, such as next-generation sequencing, has provided a lot of useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic tumors (e.g., pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, solid pseudopapillary tumors) are characterized by specific molecular alterations. The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.
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Affiliation(s)
- Michela Visani
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
| | - Giorgia Acquaviva
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
| | - Antonio De Leo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
- Division of Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Viviana Sanza
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
| | - Lidia Merlo
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
| | - Thais Maloberti
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
| | - Alba A Brandes
- Medical Oncology Department, Azienda USL/IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna 40139, Italy
| | - Enrico Franceschi
- Medical Oncology Department, Azienda USL/IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna 40139, Italy
| | - Monica Di Battista
- Medical Oncology Department, Azienda USL/IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna 40139, Italy
| | - Michele Masetti
- Division of Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40133, Italy
| | - Elio Jovine
- Division of Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40133, Italy
| | - Sirio Fiorino
- Internal Medicine Unit, Budrio Hospital Azienda USL, Bologna 40133, Italy
| | - Annalisa Pession
- Division of Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40138, Italy
| | - Giovanni Tallini
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna–Molecular Diagnostic Unit, Azienda USL di Bologna, Bologna 40138, Italy
- Division of Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
| | - Dario de Biase
- Division of Molecular Pathology Laboratory, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40138, Italy
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18
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Crinò SF, Ammendola S, Meneghetti A, Bernardoni L, Conti Bellocchi MC, Gabbrielli A, Landoni L, Paiella S, Pin F, Parisi A, Mastrosimini MG, Amodio A, Frulloni L, Facciorusso A, Larghi A, Manfrin E. Comparison between EUS-guided fine-needle aspiration cytology and EUS-guided fine-needle biopsy histology for the evaluation of pancreatic neuroendocrine tumors. Pancreatology 2021; 21:443-450. [PMID: 33390343 DOI: 10.1016/j.pan.2020.12.015] [Citation(s) in RCA: 75] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 12/09/2020] [Accepted: 12/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND/OBJECTIVES Studies comparing EUS-guided fine-needle aspiration (EUS-FNA) with EUS-guided fine-needle biopsy (EUS-FNB) for the evaluation of pancreatic neuroendocrine tumors (pNETs) are lacking. We aimed at comparing EUS-FNA with EUS-FNB in terms of Ki-67 proliferative index (PI) estimation capability, cellularity of the samples, and reliability of Ki-67 PI/tumor grading compared with surgical specimens. METHODS Patients diagnosed with pNETs on EUS and/or surgical specimens were retrospectively identified. Specimens were re-evaluated to assess Ki-67 PI feasibility, sample cellularity by manual counting, and determination of Ki-67 PI value. Outcomes in the EUS-FNA and EUS-FNB groups were compared. Kendall rank test was used for Ki-67 PI correlation between EUS and surgical specimens. Subgroup analysis including small (≤20 mm), non-functioning pNETs was performed. RESULTS Three-hundred samples from 292 lesions were evaluated: 69 EUS-FNA cytology and 231 EUS-FNB histology. Ki-67 PI feasibility was similar for EUS-FNA and EUS-FNB (91.3% vs. 95.7%, p = 0.15), while EUS-FNB performed significantly better in the subgroup of 179 small pNETs (88.2% vs. 96.1%, p = 0.04). Rate of poor cellulated (<500 cells) specimens was equal between EUS-FNA and EUS-FNB. A significant correlation for Ki-67 PI values between EUS and 92 correspondent surgical specimens was found in both groups, but it was stronger with EUS-FNB (tau = 0.626, p < 0.0001 vs. tau = 0.452, p = 0.031). Correct grading estimation was comparable between the two groups (p = 0.482). CONCLUSION Our study showed stronger correlation for Ki-67 values between EUS-FNB and surgical specimens, and that EUS-FNB outperformed EUS-FNA in the evaluation of small pNETs. EUS-FNB should become standard of care for grading assessment of suspected pNETs.
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Affiliation(s)
- Stefano Francesco Crinò
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy.
| | - Serena Ammendola
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | - Anna Meneghetti
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Laura Bernardoni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | | | - Armando Gabbrielli
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Landoni
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Salvatore Paiella
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Federico Pin
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Alice Parisi
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
| | | | - Antonio Amodio
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Luca Frulloni
- Gastroenterology and Digestive Endoscopy Unit, The Pancreas Institute, G.B. Rossi University Hospital, Verona, Italy
| | - Antonio Facciorusso
- Digestive Endoscopy Unit, Department of Medical Sciences, University of Foggia, Foggia, Italy
| | - Alberto Larghi
- Digestive Endoscopy Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Rome, Italy
| | - Erminia Manfrin
- Department of Diagnostics and Public Health, G.B. Rossi University Hospital, Verona, Italy
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19
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Kim H, Jang KT. Pathologic interpretation of endoscopic ultrasound-guided fine needle aspiration cytology/biopsy for pancreatic lesions. J Pathol Transl Med 2020; 54:367-377. [PMID: 32854488 PMCID: PMC7483032 DOI: 10.4132/jptm.2020.07.21] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/21/2020] [Indexed: 12/23/2022] Open
Abstract
Pathologic interpretation of endoscopic ultrasound–guided fine needle aspiration (EUS-FNA) cytology/biopsy specimens is one of the most challenging tasks in cytology and surgical pathology practice, as the procedure often yields minimal amounts of diagnostic material and contains contaminants, such as blood cells and normal intestinal mucosa. EUS-FNA cytology/biopsy will nevertheless become a more popular procedure for evaluation of various pancreatic lesions because they are difficult to approach with conventional endoscopic procedures. Pathologists should understand the structural differences and limitations of EUS-FNA that make pathologic diagnosis difficult. Ancillary tests are available for differential diagnosis of EUS-FNA for various pancreatic lesions. Immunostains are the most commonly used ancillary tests, and pathologists should able to choose the necessary panel for differential diagnosis. Pathologists should review clinical history and radiologic and/or EUS findings before selecting an immunostain panel and making a pathologic diagnosis. In addition, one’s threshold of malignancy should be adjusted according to the appropriate clinical setting to avoid under-evaluation of pathologic diagnoses. Clinico-pathologic correlation is essential in pathologic evaluation of EUS-FNA for pancreatic lesions. Pathologists can reduce errors by correlating clinical and radiologic findings when evaluating EUS-FNA. Some molecular tests can be applied in differential diagnosis of pancreatic neoplastic and cystic lesions. Molecular data should be used as supportive evidence of a specific disease entity, rather than direct evidence, and should be correlated with clinico-pathologic findings to avoid errors in pathologic diagnosis.
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Affiliation(s)
- Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kee-Taek Jang
- Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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20
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Ieni A, Tuccari G. Re: Assessment of preoperative pancreatic biopsy, cytological/histological review of cell-block-specimens obtained by endoscopic ultrasound-guided fine-needle aspiration: Laboratory based study. Diagn Cytopathol 2020; 48:1153-1154. [PMID: 32716581 DOI: 10.1002/dc.24555] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 07/02/2020] [Indexed: 11/12/2022]
Affiliation(s)
- Antonio Ieni
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy
| | - Giovanni Tuccari
- Department of Human Pathology in Adult and Developmental Age "Gaetano Barresi", Section of Pathology, University of Messina, Messina, Italy
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21
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Le K, Wang J, Zhang T, Guo Y, Chang H, Wang S, Zhu B. Overexpression of Mesothelin in Pancreatic Ductal Adenocarcinoma (PDAC). Int J Med Sci 2020; 17:422-427. [PMID: 32174772 PMCID: PMC7053310 DOI: 10.7150/ijms.39012] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2019] [Accepted: 01/05/2020] [Indexed: 12/11/2022] Open
Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) with difficulty in early diagnosis does not respond well to conventional treatments and has not occurred significant improvement in the overall 5-year survival rates. Mesothelin (MSLN) is a tumor differentiation antigen expressed in several solid neoplasms and a limited number of healthy tissues. Its selective expression on malignant cells makes it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. In this study, we detected the expression of MSLN in PDAC and analyzed the correlation between the expression of MSLN and clinicopathological data, so as to provide more theoretical basis for the role of MSLN in the diagnosis and treatment of PDAC. Patients and methods: Cancer and para-cancer tissues of 24 cases with PDAC were assessed by standardized immunohistochemical (IHC) detection with two kinds of anti-MSLN antibodies (EPR4509 and EPR19025-42) to detect their positive expression rates and study the correlation between the expression of MSLN and the clinicopathological data. Results: The two anti-MSLN antibodies of cancer tissues showed positive expression with tan yellow or tan brown granules diffusely distributed on the cell membrane in 22 of 24 cases with PDAC (positive rate of 91.67%), and the positive expression of the two antibodies EPR4509 and EPR19025-42 was completely consistent in all tissue samples. No expression of the two anti-MSLN antibodies was found in para-cancer tissues and the difference was statistically significant (χ2=40.615, p=0.000, p<0.05) when compared with PDAC tissues. There was no significant correlation between MSLN expression and clinicopathological data, such as gender, tumor size, location, pathological stage, differentiation degree and lymph node metastasis (p>0.05). Conclusion: MSLN was highly expressed in PDAC tissues, but not in paracancerous tissues. There was no significant correlation between MSLN expression and clinicopathological factors. The overexpression of MSLN may have promising prospects in diagnosis, targeted therapy and immunotherapy of PDAC.
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Affiliation(s)
- Kai Le
- Department of General Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
- Department of Urology Surgery, Aerospace Center Hospital, Beijing, China
| | - Jia Wang
- Department of General Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Tao Zhang
- Department of General Surgery, Liang Xiang Teaching Hospital of Capital Medical University, Beijing, China
| | - Yifan Guo
- Department of General Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Hong Chang
- Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Siyuan Wang
- Department of Rehabilitation Medicine, China-Japan Friendship Hospital, Beijing, China
| | - Bin Zhu
- Department of General Surgery, Peking University Ninth School of Clinical Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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22
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Nichetti F, Marra A, Corti F, Guidi A, Raimondi A, Prinzi N, de Braud F, Pusceddu S. The Role of Mesothelin as a Diagnostic and Therapeutic Target in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review. Target Oncol 2019; 13:333-351. [PMID: 29656320 DOI: 10.1007/s11523-018-0567-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Mesothelin is a tumor differentiation antigen, which is highly expressed in several solid neoplasms, including pancreatic cancer. Its selective expression on malignant cells and on only a limited number of healthy tissues has made it an interesting candidate for investigation as a diagnostic and prognostic biomarker and as a therapeutic target. Based on a strong preclinical rationale, a number of therapeutic agents targeting mesothelin have entered clinical trials, including immunotoxins, monoclonal antibodies, antibody-drug conjugates, cancer vaccines, and adoptive T cell therapies with chimeric antigen receptors. In pancreatic cancer, mesothelin has been investigated mainly to address two unmet issues: the urgent need for new laboratory techniques for early tumor detection and the lack of successfully targetable oncogenic alterations for patients' treatment. In this review, we describe the clinicopathological significance of mesothelin expression in pancreatic cancer initiation and progression, we summarize available studies evaluating mesothelin as a potential diagnostic and prognostic biomarker in this disease, and we discuss current evidence and future perspectives of preclinical and clinical studies testing mesothelin as a molecular target for pancreatic cancer treatment.
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Affiliation(s)
- Federico Nichetti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Antonio Marra
- Medical Oncology Unit, Azienda Ospedaliera San Paolo, Milan, Italy
| | - Francesca Corti
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Alessandro Guidi
- Medical Oncology Unit, Azienda Ospedaliera San Gerardo, Monza, Italy
| | - Alessandra Raimondi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Natalie Prinzi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
- Department of Oncology, Università degli Studi di Milano, Milan, Italy
| | - Sara Pusceddu
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy
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Jhala N, Srimunta P, Jhala D. Role of Ancillary Testing on Endoscopic US-Guided Fine Needle Aspiration Samples from Cystic Pancreatic Neoplasms. Acta Cytol 2019; 64:124-135. [PMID: 31509835 DOI: 10.1159/000502372] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2019] [Accepted: 07/22/2019] [Indexed: 12/11/2022]
Abstract
Pancreatic cysts are increasingly detected on imaging studies. Accurate determination of the cyst type is important to provide appropriate care for the patients. It is also very clear that not one single modality can provide adequate diagnostic information. A multidisciplinary approach is the key to the diagnosis of pancreatic cysts. In this setting, the role of ancillary testing, which includes biochemical testing (carcinoembryonic antigen and amylase levels in the cyst), molecular testing (e.g., KRAS, GNAS, VHL, and CTNB1), and/or immunohistochemical tests are very important to obtain an accurate diagnosis. This review will discuss helpful ancillary tests in common pancreatic cyst neoplasms and how to approach the diagnosis of pancreatic cysts.
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Affiliation(s)
- Nirag Jhala
- Department of Pathology and Laboratory Medicine, Temple University Hospital, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA,
| | - Piyachat Srimunta
- Visiting Fellow, Department of Pathology and Laboratory Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, USA
| | - Darshana Jhala
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Pathology and Laboratory Services, CMC Philadelphia VA Medical Center, Philadelphia, Pennsylvania, USA
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Layfield L. Role of Ancillary Techniques in Biliary Cytopathology Specimens. Acta Cytol 2019; 64:175-181. [PMID: 31121596 DOI: 10.1159/000498976] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Accepted: 02/14/2019] [Indexed: 12/20/2022]
Abstract
Biliary brushing cytology has become the standard of practice for the investigation of strictures of the biliary and pancreatic duct systems. The methodology however has a limitation in that it has low diagnostic sensitivity when only cytologic evaluation is used. A number of testing methodologies have been applied to brushing specimens in an attempt to improve overall sensitivity without loss of specificity. These have included DNA ploidy analysis, immunocytochemistry, individual gene mutational analysis, fluorescence in-situ hybridization (FISH), and next generation sequencing (NGS). Currently, FISH coupled with routine cytology appears to be the method of choice for improving diagnostic sensitivity. NGS shows significant promise for improvement of diagnostic sensitivity.
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Affiliation(s)
- Lester Layfield
- Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, Missouri, USA,
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Heymann JJ, Siddiqui MT. Ancillary Techniques in Cytologic Specimens Obtained from Solid Lesions of the Pancreas: A Review. Acta Cytol 2019; 64:103-123. [PMID: 30970350 DOI: 10.1159/000497153] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Accepted: 01/22/2019] [Indexed: 12/21/2022]
Abstract
Advanced methods of molecular characterization have elucidated the genetic, epigenetic, and proteomic alterations associated with the broad spectrum of pancreatic disease, particularly neoplasia. Next-generation sequencing, in particular, has revealed the genomic diversity among pancreatic ductal adenocarcinoma, neuroendocrine and acinar tumors, solid pseudopapillary neoplasm, and other pancreatico-biliary neoplasms. Differentiating these entities from one another by morphologic analysis alone may be challenging, especially when examining the small quantities of diagnostic material inherent to cytologic specimens. In order to enhance the sensitivity and specificity of pancreatic cytomorphology, multiple diagnostic, prognostic, and predictive ancillary tests have been and continue to be developed. Although a great number of such tests have been developed for evaluation of specimens collected from cystic lesions and strictures, ancillary techniques also play a significant role in the evaluation of cytologic specimens obtained from solid lesions of the pancreas. Furthermore, while some tests have been developed to differentiate diagnostic entities from one another, others have been developed to simply identify dysplasia and malignancy. Ancillary studies are particularly important in the subset of cases for which cytomorphologic analysis provides a result that is equivocal or insufficient to guide clinical management. Selection of appropriate ancillary testing modalities requires familiarity with both their methodology and the molecular basis of the pancreatic diseases for which testing is being performed.
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Affiliation(s)
- Jonas J Heymann
- Division of Cytopathology, Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA,
| | - Momin T Siddiqui
- Division of Cytopathology, Department of Pathology and Laboratory Medicine, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, New York, USA
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26
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Weiss MJ. The value of cytology in the management of patients with pancreatic cysts. Cancer Cytopathol 2019; 127:141-142. [PMID: 30668886 DOI: 10.1002/cncy.22095] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Matthew John Weiss
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
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27
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Layfield LJ, Esebua M, Ang J, Alnijoumi MM, Sohal HS, Hammer RD, Prabhakaran N, Schmidt RL. Cell block cellularity: A comparison of two fixatives and their impact on cellularity. Diagn Cytopathol 2018; 47:417-420. [DOI: 10.1002/dc.24118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2018] [Revised: 09/07/2018] [Accepted: 10/19/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Lester J. Layfield
- Department of Pathology & Anatomical SciencesUniversity of Missouri Columbia Missouri
| | - Magda Esebua
- Department of Pathology & Anatomical SciencesUniversity of Missouri Columbia Missouri
| | - Jonathan Ang
- Department of Internal Medicine, Division of PulmonologyUniversity of Missouri Columbia Missouri
| | - Mohammed M. Alnijoumi
- Department of Internal Medicine, Division of PulmonologyUniversity of Missouri Columbia Missouri
| | - Harijyot S. Sohal
- Department of Internal Medicine, Division of PulmonologyUniversity of Missouri Columbia Missouri
| | - Richard D. Hammer
- Department of Pathology & Anatomical SciencesUniversity of Missouri Columbia Missouri
| | - Nitya Prabhakaran
- Department of Pathology & Anatomical SciencesUniversity of Missouri Columbia Missouri
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28
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Matsuda Y, Esaka S, Suzuki A, Hamashima Y, Imaizumi M, Matsukawa M, Fujii Y, Aida J, Takubo K, Ishiwata T, Nishimura M, Arai T. Abnormal immunolabelling of SMAD4 in cell block specimens to distinguish malignant and benign pancreatic cells. Cytopathology 2018; 30:201-208. [PMID: 30421464 DOI: 10.1111/cyt.12653] [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] [Received: 05/08/2018] [Revised: 10/15/2018] [Accepted: 10/31/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Accurate diagnosis of malignant and benign pancreatic lesions can be challenging, especially with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) samples that are small and/or degraded. In the present study, we determined how to best evaluate abnormal SMAD4 expression by immunohistochemical staining on cell block specimens from EUS-FNA samples. RESULTS In surgically resected pancreas, when abnormal SMAD4 immunolabelling was evaluated as negative SMAD4 expression, the sensitivity was low (33%), but when it was evaluated as decreased SMAD4 expression, the sensitivity improved (53%). Specificity and positive predictive value were high for both evaluations. There were no false-positive cases. In cell block specimens, decreased SMAD4 expression showed 47% sensitivity and 72% specificity, while negative SMAD4 expression showed lower sensitivity (20%) and higher specificity (100%). Both evaluations in cell block specimens showed lower sensitivity and specificity compared to resected specimens. False-positive and -negative rates were higher for cell blocks than for resected specimens. CONCLUSIONS Decreased SMAD4 immunolabelling provided improved sensitivity as compared to negative SMAD4 immunolabelling; therefore, it is important to compare SMAD4 expression in a sample to its expression in normal cells. Abnormal SMAD4 labelling showed low sensitivity and high specificity; therefore, SMAD4 staining using EUS-FNA samples might be helpful to detect malignancies that possess SMAD4 gene abnormalities.
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Affiliation(s)
- Yoko Matsuda
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Shikine Esaka
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Akemi Suzuki
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Yuri Hamashima
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Masayuki Imaizumi
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Miho Matsukawa
- Department of Endoscopy, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Yuko Fujii
- Department of Endoscopy, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Junko Aida
- Research Team for Geriatric Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan
| | - Kaiyo Takubo
- Research Team for Geriatric Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan
| | - Toshiyuki Ishiwata
- Research Team for Geriatric Pathology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, Itabashi-ku, Tokyo, Japan
| | - Makoto Nishimura
- Department of Endoscopy, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
| | - Tomio Arai
- Department of Pathology, Tokyo Metropolitan Geriatric Hospital, Itabashi-ku, Tokyo, Japan
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López-Ramírez AN, Villegas-González LF, Serrano-Arévalo ML, Flores-Hernández L, Lino-Silva LS, González-Mena LE. Reclassification of lesions in biopsies by fine-needle aspiration of pancreas and biliary tree using Papanicolaou classification. J Gastrointest Oncol 2018; 9:847-852. [PMID: 30505584 PMCID: PMC6219961 DOI: 10.21037/jgo.2018.06.06] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 05/30/2018] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Our aim was to evaluate the application of the classification of the Papanicolaou Cytopathology Society for the report of biopsies by fine-needle aspiration (FNA) of pancreas and bile duct. METHODS The FNAs obtained consecutively during 1 year were analyzed. Descriptive statistics were performed and sensitivity, specificity, positive predictive value, negative predictive value, and cytohistological correlation were determined. The reference standard test was the histopathological study. RESULTS A total of 134 cases of FNA were reclassified with ultrasound guidance according to the classification of the Papanicolaou Society, the median age was 59 years (range, 25-80 years). A case interpreted as non-diagnostic was reclassified to category 4 and 3 cases with atypical cells were reclassified to category 5. All malignant cases remained unchanged. Surgical follow-up was performed in 35 patients (26.1%), with a cytohistological concordance in 21 cases (91.3%) and 2 discordant cases (8.7%), the reasons for the discrepancy were due to sampling error, one of them with scarce material to make a diagnosis of higher category, the other case with partial agreement, because cytology was observed atypical cylindrical epithelium, with histology of grade 2 neuroendocrine neoplasia and low grade mucinous intraepithelial neoplasia. In general, the sensitivity and specificity were 100% and 75% respectively, the positive predictive value 88% and the negative predictive value 100%. CONCLUSIONS The FNA guided with endoscopic ultrasound (EUS) and interpreted according to the Papanicolaou Cytopathology Society Classification is an accurate method to evaluate pancreatic and biliary tract lesions with a high positive predictive value of 88%.
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Affiliation(s)
| | | | | | | | - Leonardo S Lino-Silva
- Department of Surgical Pathology, Instituto Nacional de Cancerología, México City, México
| | - Ludwig E González-Mena
- Department of Cytopathology, Hospital General de Mexico "Gerardo Liceaga", Mexico City, Mexico
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30
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Abstract
The diagnostic approach to pancreaticobiliary disease requires a multidisciplinary team in which the cytopathologist plays a crucial role. Fine-needle aspiration, obtained by endoscopic ultrasound, is the diagnostic test of choice for pancreatic lesions. Preoperative clinical management depends on many factors, many of which rely on accurate cytologic assessment. Pancreaticobiliary cytology is wrought with diagnostic pitfalls. Clinical history, imaging studies, cytology samples, and ancillary tests, including immunohistochemistry, biochemical analysis, and genetic sequencing, are integral to forming a complete diagnosis and guiding optimal patient management. This article reviews clinical aspects and the diagnostic work-up of commonly encountered diagnostic entities within the field of pancreatic cytology.
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Affiliation(s)
- Raza S Hoda
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
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31
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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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32
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The new guidelines of Papanicolaou Society of Cytopathology for respiratory specimens: Assessment of risk of malignancy and diagnostic yield in different cytological modalities. Diagn Cytopathol 2018; 46:725-729. [DOI: 10.1002/dc.24036] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Revised: 06/18/2018] [Accepted: 06/29/2018] [Indexed: 12/19/2022]
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33
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Zhai J. UroVysion Multi-Target Fluorescence in situ Hybridization Assay for the Detection of Malignant Bile Duct Brushing Specimens: A Comparison with Routine Cytology. Acta Cytol 2018; 62:295-301. [PMID: 29734171 DOI: 10.1159/000488636] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Accepted: 03/21/2018] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Routine bile duct brushing cytology is an important diagnostic tool in the evaluation of bile duct stricture. The purpose of this study was to evaluate the performance of the UroVysion fluorescence in situ hybridization (FISH) assay for the detection of malignant bile duct brushing specimens. STUDY DESIGN Thirty-five bile duct brushing specimens were included in the study. The FISH assay utilized the commercially available UroVysion probes. The indeterminate cytology results were considered as negative for statistical analysis. RESULTS Twenty-two of 35 patients were diagnosed as having malignancy based on tissue diagnosis or clinical progression of disease by image assessment. The sensitivity of routine cytology and FISH for the detection of malignancy was 14% (3/22) and 55% (12/22), respectively (p = 0.003). The specificity of routine cytology and FISH was 100% (13/13) and 62% (8/13), respectively (p = 0.025). The false-positive rate for routine cytology and FISH was 0% (0/13) and 38% (5/13), respectively. CONCLUSIONS Our study shows that FISH is significantly more sensitive than routine cytology for the detection of malignancy in bile duct brushing specimens. However, in our study, the specificity of FISH was poor compared to the excellent specificity of routine cytology. The compromised specificity of FISH may limit its utility in the detection of malignant bile duct brushing specimens.
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34
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de Biase D, Visani M, Acquaviva G, Fornelli A, Masetti M, Fabbri C, Pession A, Tallini G. The Role of Next-Generation Sequencing in the Cytologic Diagnosis of Pancreatic Lesions. Arch Pathol Lab Med 2018; 142:458-464. [PMID: 29565213 DOI: 10.5858/arpa.2017-0215-ra] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
CONTEXT - Integration of the analysis of genetic markers with endoscopic ultrasound-guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements. OBJECTIVE - To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions. DATA SOURCES - For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000-2017. CONCLUSIONS - KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.
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Affiliation(s)
| | | | | | | | | | | | | | - Giovanni Tallini
- From the Department of Pharmacy and Biotechnology (Dipartimento di Farmacia e Biotecnologie)-Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna, Bologna, Italy (Dr de Biase and Ms Pession); the Department of Medicine (Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale)-Molecular Diagnostic Unit, Azienda USL di Bologna, University of Bologna School of Medicine, Bologna, Italy (Drs Visani and Tallini and Ms Acquaviva); the Unit of Anatomic Pathology, Azienda USL-Maggiore Hospital, Bologna, Italy (Dr Fornelli); and the Units of Surgery (Dr Masetti) and Gastroenterology and Digestive Endoscopy (Dr Fabbri), Azienda USL Bologna Bellaria-Maggiore Hospitals, Bologna, Italy
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Wright PK, Shelton DA, Holbrook MR, Thiryayi SA, Narine N, Slater D, Rana DN. Outcomes of endoscopic ultrasound-guided pancreatic FNAC diagnosis for solid and cystic lesions at Manchester Royal Infirmary based upon the Papanicolaou Society of Cytopathology pancreaticobiliary terminology classification scheme. Cytopathology 2017; 29:71-79. [DOI: 10.1111/cyt.12502] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/03/2017] [Indexed: 12/12/2022]
Affiliation(s)
- P. K. Wright
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - D. A. Shelton
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - M. R. Holbrook
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - S. A. Thiryayi
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - N. Narine
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - D. Slater
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
| | - D. N. Rana
- Manchester Cytology Centre; Manchester Royal Infirmary; Manchester University NHS Foundation Trust; Manchester UK
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Tanaka M, Fernández-Del Castillo C, Kamisawa T, Jang JY, Levy P, Ohtsuka T, Salvia R, Shimizu Y, Tada M, Wolfgang CL. Revisions of international consensus Fukuoka guidelines for the management of IPMN of the pancreas. Pancreatology 2017; 17:738-753. [PMID: 28735806 DOI: 10.1016/j.pan.2017.07.007] [Citation(s) in RCA: 1138] [Impact Index Per Article: 142.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 07/12/2017] [Accepted: 07/12/2017] [Indexed: 02/06/2023]
Abstract
The management of intraductal papillary mucinous neoplasm (IPMN) continues to evolve. In particular, the indications for resection of branch duct IPMN have changed from early resection to more deliberate observation as proposed by the international consensus guidelines of 2006 and 2012. Another guideline proposed by the American Gastroenterological Association in 2015 restricted indications for surgery more stringently and recommended physicians to stop surveillance if no significant change had occurred in a pancreatic cyst after five years of surveillance, or if a patient underwent resection and a non-malignant IPMN was found. Whether or not it is safe to do so, as well as the method and interval of surveillance, has generated substantial debate. Based on a consensus symposium held during the meeting of the International Association of Pancreatology in Sendai, Japan, in 2016, the working group has revised the guidelines regarding prediction of invasive carcinoma and high-grade dysplasia, surveillance, and postoperative follow-up of IPMN. As the working group did not recognize the need for major revisions of the guidelines, we made only minor revisions and added most recent articles where appropriate. The present guidelines include updated information and recommendations based on our current understanding, and highlight issues that remain controversial or where further research is required.
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Affiliation(s)
- Masao Tanaka
- Department of Surgery, Shimonoseki City Hospital, Shimonoseki, Japan.
| | | | - Terumi Kamisawa
- Department of Gastroenterology, Komagome Metropolitan Hospital, Tokyo, Japan
| | - Jin Young Jang
- Division of Hepatobiliary-Pancreatic Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul, South Korea
| | - Philippe Levy
- Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, Hopital Beaujon, Clichy Cedex, France
| | - Takao Ohtsuka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Roberto Salvia
- Department of General and Pancreatic Surgery, The Pancreas Institute, University of Verona Hospital Trust, Verona, Italy
| | - Yasuhiro Shimizu
- Dept. of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | - Minoru Tada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Christopher L Wolfgang
- Cameron Division of Surgical Oncology and The Sol Goldman Pancreatic Cancer Research Center, Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
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Saieg MA, Munson V, Colletti S, Nassar A. Impact of Pancreatic Cyst Fluid CEA Levels on the Classification of Pancreatic Cysts Using the Papanicolaou Society of Cytology Terminology System for Pancreaticobiliary Cytology. Diagn Cytopathol 2017; 45:101-106. [DOI: 10.1002/dc.23633] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 09/29/2016] [Accepted: 10/21/2016] [Indexed: 01/04/2023]
Affiliation(s)
- Mauro Ajaj Saieg
- Department of Pathology; Santa Casa Medical School; Sao Paulo Brazil
- Department of Pathology; Fleury Laboratories; Sao Paulo Brazil
| | - Valerie Munson
- Department of Laboratory Medicine and Pathology; Mayo Clinic; Jacksonville Florida
| | - Shanna Colletti
- Department of Laboratory Medicine and Pathology; Mayo Clinic; Jacksonville Florida
| | - Aziza Nassar
- Department of Laboratory Medicine and Pathology; Mayo Clinic; Jacksonville Florida
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Reid MD, Lewis MM, Willingham FF, Adsay NV. The Evolving Role of Pathology in New Developments, Classification, Terminology, and Diagnosis of Pancreatobiliary Neoplasms. Arch Pathol Lab Med 2017; 141:366-380. [PMID: 28055239 DOI: 10.5858/arpa.2016-0262-sa] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Pancreatobiliary tract lesions are increasingly being discovered because of more sensitive imaging modalities. Magnetic resonance imaging has identified incidental pancreatic cysts in 13.5% of patients of progressively increasing age. Pancreatobiliary tissue is more accessible through endoscopic ultrasound and magnetic resonance imaging-guided biopsy procedures, and is now an integral part of pathologists' routine practice. Accordingly, several new tumor categories have been recently recognized, including intraductal tubulopapillary neoplasm, a new addition to tumoral intraepithelial neoplasms. Other entities have been reclassified, including the recent transition to 2-tiered grading of preinvasive neoplasms, as well as new perspectives on the distinctive biologic behavior of oncocytic intraductal papillary mucinous neoplasms (IPMNs) compared with other IPMN subtypes. This has led to proposals for revised staging of virtually every segment of the pancreatobiliary tree, with theranostic markers becoming an integral part of workup. Ki-67 is now an integral part of the classification of neuroendocrine tumors, with new definitions of "high-grade neuroendocrine carcinoma." Although bile duct brushings have opened new avenues for diagnosis, their sensitivity remains low and often requires concomitant fluorescent in situ hybridization to better define ambiguous cases. Various molecular pathways have been elucidated for pancreatic cysts, including KRAS for ductal neoplasia, GNAS for intestinal IPMNs, RNF3 for mucinous cysts, and VHL for serous cystic neoplasms, all key players in diagnostic workup. Integration of these updates into our understanding of pancreatobiliary disease requires active engagement of pathologists for appropriate specimen triage, judicious interpretation of results, and incorporation into reporting and staging. They also provide exciting opportunities for targeted therapy.
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Affiliation(s)
| | | | | | - N Volkan Adsay
- From the Departments of Pathology (Drs Reid, Lewis, and Adsay) and Digestive Diseases (Dr Willingham), Emory University School of Medicine, Atlanta, Georgia
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39
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Virk RK, Gamez R, Mehrotra S, Atieh M, Barkan GA, Wojcik EM, Pambuccian SE. Variation of cytopathologists' use of the indeterminate diagnostic categories "atypical" and "suspicious for malignancy" in the cytologic diagnosis of solid pancreatic lesions on endoscopic ultrasound-guided fine-needle aspirates. Diagn Cytopathol 2016; 45:3-13. [PMID: 27873469 DOI: 10.1002/dc.23565] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Accepted: 08/04/2016] [Indexed: 12/17/2022]
Abstract
Indeterminate cytologic diagnoses in endoscopic ultrasound guided fine needle aspiration biopsy (EUS-FNA) of solid pancreatic lesions include the diagnostic categories "atypical" (ATY) and "suspicious for malignancy" (SUSP), which are used at variable rates and are associated with variable underlying risk of malignancy. The aim of this study was to determine individual cytopathologists' rates of indeterminate diagnoses in EUS-FNA of solid pancreatic lesions and their relationship to cytopathologists' experience and volume of pancreatic EUS-FNA examined, as well as the potential impact of departmental consensus review on indeterminate diagnoses. DESIGN The diagnostic rates of ATY and SUSP and their underlying risk of malignancy were calculated for six cytopathologists who diagnosed 1,114 of 1,225 EUS-FNA of solid pancreatic lesions from 1/1/2001 to 9/15/2014, and were then compared for the periods before and after the implementation of departmental consensus review during 2009. RESULTS The six cytopathologists diagnosed 10% of cases as indeterminate; 82 (7.4%) as "atypical" and 29 (2.6%) as "suspicious". The individual cytopathologists' indeterminate diagnosis rates varied twofold (6.67-12.80%) and did not correlate with their experience, total or annual volume of EUS-FNAs. Of the 56/99 (56.57%) cases with follow-up, the underlying rate of malignancy was 47% (35/75; for "atypical" and 87.5% (21/24); for "suspicious"). The underlying rates of malignancy were 33-67% for "atypical" and 80-100% for "suspicious" diagnoses made by individual cytopathologists. The rate of indeterminate diagnoses decreased from 11.55 to 7.88% after the implementation of departmental consensus review. CONCLUSION Individual cytopathologists' rates of indeterminate diagnoses and their significance vary; however, consensus review is helpful in reducing these rates. Diagn. Cytopathol. 2017;45:3-13. © 2016 Wiley Periodicals, Inc.
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Affiliation(s)
- Renu K Virk
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Roberto Gamez
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Swati Mehrotra
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Mohammed Atieh
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Güliz A Barkan
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Eva M Wojcik
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
| | - Stefan E Pambuccian
- Department of Pathology, Loyola University Medical Center, Maywood, Illinois
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40
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Raddaoui EM, Almadi MA, Aljebreen AM, Alsaif FA, AlShedoukhy AA, Al-Lehibi AH, Almohameed KA, Tsolakis AV, AlAbbadi MA, Almutrafi AR. Differential diagnosis between pancreatic neuroendocrine and solid pseudopapillary neoplasms on endoscopic ultrasound-guided fine-needle aspiration. An immunohistochemical study. Saudi Med J 2016; 37:744-749. [PMID: 27381533 PMCID: PMC5018637 DOI: 10.15537/smj.2016.7.14212] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2015] [Accepted: 05/25/2016] [Indexed: 01/17/2023] Open
Abstract
OBJECTIVES To evaluate the role of applying a limited panel of immunohistochemical stains on the cellblock preparation from samples obtained by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the aim of differentiating solid pseudopapillary neoplasms (SPNs) from neuroendocrine tumors (NETs). METHODS We retrospectively retrieved all the EUS-FNAs of the pancreas that have a diagnosis of NET or SPN that were performed at 2 tertiary care hospitals in Riyadh, Kingdom of Saudi Arabia from May 2004 to December 2014. Diff-Quik, Papanicolaou, and Immunohistochemistry stains on cellblock preparations were performed. RESULTS Twenty cases were available (16 pancreatic neuroendocrine tumors (pNETs) and 4 SPNs). The pNETs were immunoreactive for synaptophysin, chromogranin A and CD56 while E-cadherin was diffusely to focally cytoplasmic positive. β-catenin was negative or showed focal cytoplasmic immunoreactivity. In comparison, SPNs were positive for vimentin, CD10, CD-56, focally positive for progesterone receptors and synaptophysin, and revealed nuclear immunostaining for β-catenin. They were negative for chromogranin A and E-cadherin. CONCLUSION Based on EUS-FNA samples, nuclear immunoreactivity for β-catenin with loss of membranous immunostaining for E-Cadherin can potentially facilitate differentiating SPNs from pNETs.
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Affiliation(s)
- Emad M Raddaoui
- Department of Pathology, College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia. E-mail.
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41
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McKinley M, Newman M. Observations on the application of the Papanicolaou Society of Cytopathology standardised terminology and nomenclature for pancreaticobiliary cytology. Pathology 2016; 48:353-6. [DOI: 10.1016/j.pathol.2016.03.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2015] [Revised: 03/09/2016] [Accepted: 03/14/2016] [Indexed: 12/13/2022]
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42
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Perez-Machado MA. Pancreatic cytology: standardised terminology and nomenclature. Cytopathology 2016; 27:157-60. [DOI: 10.1111/cyt.12347] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/08/2016] [Indexed: 12/18/2022]
Affiliation(s)
- M. A. Perez-Machado
- Department of Cellular Pathology; Royal Free, Hampstead NHS Trust; London UK
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43
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Puri R, Manrai M, Thandassery RB, Alfadda AA. Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas. World J Gastrointest Endosc 2016. [PMID: 26839647 DOI: 10.4253/wjge.v8.i2.67.] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas.
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Affiliation(s)
- Rajesh Puri
- Rajesh Puri, Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon 122001, Haryana, India
| | - Manish Manrai
- Rajesh Puri, Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon 122001, Haryana, India
| | - Ragesh Babu Thandassery
- Rajesh Puri, Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon 122001, Haryana, India
| | - Abdulrahman A Alfadda
- Rajesh Puri, Institute of Digestive and Hepatobiliary Sciences, Medanta, The Medicity, Gurgaon 122001, Haryana, India
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44
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Puri R, Manrai M, Thandassery RB, Alfadda AA. Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas. World J Gastrointest Endosc 2016; 8:67-76. [PMID: 26839647 PMCID: PMC4724032 DOI: 10.4253/wjge.v8.i2.67] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 10/30/2015] [Accepted: 11/17/2015] [Indexed: 02/05/2023] Open
Abstract
Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas.
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45
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Manning MA, Srivastava A, Paal EE, Gould CF, Mortele KJ. Nonepithelial Neoplasms of the Pancreas: Radiologic-Pathologic Correlation, Part 1—Benign Tumors:From the Radiologic Pathology Archives. Radiographics 2016; 36:123-41. [DOI: 10.1148/rg.2016150212] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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46
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Eloubeidi MA, Decker GA, Chandrasekhara V, Chathadi KV, Early DS, Evans JA, Fanelli RD, Fisher DA, Foley K, Hwang JH, Jue TL, Lightdale JR, Pasha SF, Saltzman JR, Sharaf R, Shergill AK, Cash BD, DeWitt JM. The role of endoscopy in the evaluation and management of patients with solid pancreatic neoplasia. Gastrointest Endosc 2016; 83:17-28. [PMID: 26706297 DOI: 10.1016/j.gie.2015.09.009] [Citation(s) in RCA: 88] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
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47
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Gleeson FC, Levy MJ. The evolving field of genomic biomarkers to characterize pancreatic cystic neoplasia by EUS-guided FNA. Gastrointest Endosc 2016; 83:149-50. [PMID: 26227930 DOI: 10.1016/j.gie.2015.07.032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2015] [Accepted: 07/17/2015] [Indexed: 02/08/2023]
Affiliation(s)
- Ferga C Gleeson
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Michael J Levy
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
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48
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Fior-Gozlan M, Giovannini D, Rabeyrin M, Mc Leer-Florin A, Laverrière MH, Bichard P. Monocentric study of bile aspiration associated with biliary brushing performed during endoscopic retrograde cholangiopancreatography in 239 patients with symptomatic biliary stricture. Cancer Cytopathol 2015; 124:330-9. [PMID: 26700399 DOI: 10.1002/cncy.21667] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Revised: 11/16/2015] [Accepted: 11/17/2014] [Indexed: 12/15/2022]
Abstract
BACKGROUND The cytologic diagnosis obtained by brushing or biopsy in malignant biliary strictures is considered to be highly specific but poorly sensitive. The diagnostic association of biliary brushing and bile exfoliate cytology has been suggested but is rarely performed in clinical practice. The objective of this study was to assess the diagnostic performance of bile aspiration associated with biliary brushing during therapeutic endoscopic retrograde cholangiopancreatography (ERCP). METHODS From 2004 to 2009, 239 consecutive patients who underwent ERCP were included in the study. The biliary strictures were considered clinically benign in 26% of patients, uncertain in 25%, and malignant in 49%. The 298 cytologic samples collected were divided in 3 groups: bile aspiration alone (26%), biliary brushing alone (20%), and bile aspiration combined with brushing (54%). The definitive diagnosis of malignancy was obtained by biopsy, surgery, and fine-needle aspiration or was determined by an unfavorable disease course. RESULTS The cytologic diagnoses were as follows: 149 samples were benign (50%), 114 were malignant (38%), 34 had atypia (12%), and 1 had no diagnostic value. The procedure output values were as follows: for bile aspiration alone, sensitivity was 56.4%, specificity was 93.9%, the positive predictive value (PPV) was 91.7%, and the negative predictive value (NPV) was 64.6%; for brushing alone, sensitivity was 62.5%, both specificity and the PPV were 100%, and the NPV was 73%; and, for bile aspiration and brushing combined, sensitivity was 81%, both specificity and the PPV were 100%, and the NPV was 75%. CONCLUSIONS For patients who have symptomatic biliary stricture, bile aspiration during ERCP is a simple and safe procedure. Bile aspiration combined with brushing significantly increases the yield of cytology for malignant biliary tumors (sensitivity, 81%), particularly in cholangiocarcinomas. Cancer Cytopathol 2016;124:330-9. © 2015 American Cancer Society.
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Affiliation(s)
| | - Diane Giovannini
- Pathology Department, Grenoble University Hospital, Grenoble, France
| | - Maud Rabeyrin
- Pathology Department, Edouard Herriot Hospital, Lyon, France
| | | | | | - Philippe Bichard
- Endoscopy Department, Grenoble University Hospital, Grenoble, France
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Alkaade S, Chahla E, Levy M. Role of endoscopic ultrasound-guided fine-needle aspiration cytology, viscosity, and carcinoembryonic antigen in pancreatic cyst fluid. Endosc Ultrasound 2015; 4:299-303. [PMID: 26643697 PMCID: PMC4672587 DOI: 10.4103/2303-9027.170417] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Due to the advances and increased utility of abdominal cross-sectional imaging, the diagnosis of pancreatic cysts continues to increase. Many endosonographers, pancreatologists, and surgeons consider endoscopic ultrasound (EUS) to be an essential tool in the management of pancreatic cystic lesions (PCLs). EUS can help distinguish between mucinous and nonmucinous lesions and may identify the specific cyst type. EUS achieves these goals by delineating the cyst morphology, identifying high risk stigmata and worrisome features, and through image-guided fine-needle aspiration (FNA) and cyst fluid analysis. However, recent consensus statements have called to question the utility and diminished the role of EUS in this setting. The aim of this review is to assess the role and advances of EUS-FNA in pancreatic cyst fluid analysis, specifically in terms of fluid cytology, viscosity, and carcinoembryonic antigen (CEA) analysis.
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Affiliation(s)
- Samer Alkaade
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, Missouri, USA
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50
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Fu LY, Mitchell KA, Cai G. Clear cell hepatocellular carcinoma diagnosed by bile duct brushing cytology. Diagn Cytopathol 2015; 44:147-51. [DOI: 10.1002/dc.23397] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 10/22/2015] [Accepted: 11/15/2015] [Indexed: 11/06/2022]
Affiliation(s)
- Li-Ying Fu
- Department of Pathology; Yale University School of Medicine; New Haven Connecticut
| | - Kisha A. Mitchell
- Department of Pathology; Yale University School of Medicine; New Haven Connecticut
| | - Guoiping Cai
- Department of Pathology; Yale University School of Medicine; New Haven Connecticut
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