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Lucocq J, Haugk B, Parkinson D, Darne A, Joseph N, Hawkyard J, White S, Mownah O, Menon K, Furukawa T, Inoue Y, Hirose Y, Sasahira N, Mittal A, Samra J, Sheen A, Feretis M, Balakrishnan A, Ceresa C, Davidson B, Pande R, Dasari BVM, Tanno L, Karavias D, Helliwell J, Young A, Nunes Q, Urbonas T, Silva M, Gordon-Weeks A, Barrie J, Gomez D, van Laarhoven S, Nawara H, Doyle J, Bhogal R, Harrison E, Roalso M, Ciprani D, Aroori S, Ratnayake B, Koea J, Capurso G, Bellotti R, Stättner S, Alsaoudi T, Bhardwaj N, Jeffery F, Connor S, Cameron A, Jamieson N, Roberts K, Soreide K, Gill AJ, Pandanaboyana S. Precursor Epithelial Subtypes of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasms (A-IPMN): Clinicopathological Features, Recurrence and Response to Adjuvant Chemotherapy. Ann Surg Oncol 2024; 31:7023-7032. [PMID: 38961040 PMCID: PMC11413116 DOI: 10.1245/s10434-024-15677-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 06/10/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND The clinico-oncological outcomes of precursor epithelial subtypes of adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) are limited to small cohort studies. Differences in recurrence patterns and response to adjuvant chemotherapy between A-IPMN subtypes are unknown. METHODS Clincopathological features, recurrence patterns and long-term outcomes of patients undergoing pancreatic resection (2010-2020) for A-IPMN were reported from 18 academic pancreatic centres worldwide. Precursor epithelial subtype groups were compared using uni- and multivariate analysis. RESULTS In total, 297 patients were included (median age, 70 years; male, 78.9%), including 54 (18.2%) gastric, 111 (37.3%) pancreatobiliary, 80 (26.9%) intestinal and 52 (17.5%) mixed subtypes. Gastric, pancreaticobiliary and mixed subtypes had comparable clinicopathological features, yet the outcomes were significantly less favourable than the intestinal subtype. The median time to recurrence in gastric, pancreatobiliary, intestinal and mixed subtypes were 32, 30, 61 and 33 months. Gastric and pancreatobiliary subtypes had worse overall recurrence (p = 0.048 and p = 0.049, respectively) compared with the intestinal subtype but gastric and pancreatobiliary subtypes had comparable outcomes. Adjuvant chemotherapy was associated with improved survival in the pancreatobiliary subtype (p = 0.049) but not gastric (p = 0.992), intestinal (p = 0.852) or mixed subtypes (p = 0.723). In multivariate survival analysis, adjuvant chemotherapy was associated with a lower likelihood of death in pancreatobiliary subtype, albeit with borderline significance [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.31-1.01; p = 0.058]. CONCLUSIONS Gastric, pancreatobiliary and mixed subtypes have comparable recurrence and survival outcomes, which are inferior to the more indolent intestinal subtype. Pancreatobiliary subtype may respond to adjuvant chemotherapy and further research is warranted to determine the most appropriate adjuvant chemotherapy regimens for each subtype.
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Affiliation(s)
- James Lucocq
- Department of General Surgery, NHS Lothian, Edinburgh, UK
| | - Beate Haugk
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Daniel Parkinson
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Antony Darne
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Nejo Joseph
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Jake Hawkyard
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Steve White
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK
| | - Omar Mownah
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, Denmark Hill, London, UK
| | - Krishna Menon
- Department of Hepatobiliary and Pancreatic Surgery, King's College Hospital, Denmark Hill, London, UK
| | - Takaki Furukawa
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Inoue
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yuki Hirose
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Naoki Sasahira
- Hepato-Biliary-Pancreatic Medicine Department, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | | | - Jas Samra
- Royal North Shore Hospital, Sydney, NSW, Australia
| | - Amy Sheen
- Department of Anatomical Pathology, Royal North Shore Hospital, New South Wales Health Pathology, Sydney, NSW, Australia
| | - Michael Feretis
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Anita Balakrishnan
- Cambridge Hepatobiliary and Pancreatic Surgery Unit, Addenbrooke's Hospital, Cambridge, UK
| | - Carlo Ceresa
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Brian Davidson
- Hepatobiliary and Pancreatic Surgery Unit, The Royal Free Hospital, London, UK
| | - Rupaly Pande
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Bobby V M Dasari
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Lulu Tanno
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Dimitrios Karavias
- Hepatobiliary and Pancreatic Surgery Unit, University Hospital Southampton, Southampton, UK
| | - Jack Helliwell
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Alistair Young
- Hepatobiliary and Pancreatic Surgery Unit, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Quentin Nunes
- Department of Hepatopancreatobiliary Surgery, East Lancashire Teaching Hospitals NHS Trust, Lancashire, UK
| | - Tomas Urbonas
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Lancashire, UK
| | - Michael Silva
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Lancashire, UK
| | - Alex Gordon-Weeks
- Oxford Hepato-Pancreato-Biliary Surgical Unit, Oxford University Hospitals NHS Foundation Trust, Lancashire, UK
| | - Jenifer Barrie
- Nottingham Hepato-Pancreatico-Biliary Service, Nottingham University Hospitals NHS Foundation Trust, Lancashire, UK
| | - Dhanny Gomez
- Nottingham Hepato-Pancreatico-Biliary Service, Nottingham University Hospitals NHS Foundation Trust, Lancashire, UK
| | - Stijn van Laarhoven
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK
| | - Hossam Nawara
- Department of Hepatobiliary and Pancreatic Surgery, University Hospitals Bristol & Weston NHS Foundation Trust, Bristol, UK
| | - Joseph Doyle
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ricky Bhogal
- Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, UK
| | - Ewen Harrison
- Department of Clinical Surgery, University of Edinburgh, Edinburgh, UK
| | - Marcus Roalso
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Deborah Ciprani
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Somaiah Aroori
- Hepatopancreatobiliary Unit, University Hospitals Plymouth NHS Trust, Plymouth, UK
| | - Bathiya Ratnayake
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, New Zealand
| | - Jonathan Koea
- Hepato-Pancreatico-Biliary/Upper Gastrointestinal Unit, North Shore Hospital, Auckland, New Zealand
| | - Gabriele Capurso
- Pancreatico-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute IRCCS, Vita-Salute San Raffaele University, Milan, Italy
| | - Ruben Bellotti
- Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbrusk, Innsbruck, Austria
| | - Stefan Stättner
- Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbrusk, Innsbruck, Austria
| | - Tareq Alsaoudi
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Neil Bhardwaj
- Leicester Hepatopancreatobiliary Unit, University Hospitals of Leicester NHS Trust, Leicester, UK
| | - Fraser Jeffery
- Department of General and Vascular Surgery, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand
| | - Saxon Connor
- Department of General and Vascular Surgery, Christchurch Hospital, Canterbury District Health Board, Christchurch, New Zealand
| | - Andrew Cameron
- Wolfson Wohl Cancer Research Centre, Research Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Nigel Jamieson
- Wolfson Wohl Cancer Research Centre, Research Institute of Cancer Sciences, University of Glasgow, Glasgow, UK
| | - Keith Roberts
- Hepatobiliary and Pancreatic Surgery Unit, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Kjetil Soreide
- Department of Gastrointestinal Surgery, Stavanger University Hospital, Stavanger, Norway
| | - Anthony J Gill
- Royal North Shore Hospital, Sydney, NSW, Australia
- Department of Anatomical Pathology, Royal North Shore Hospital, New South Wales Health Pathology, Sydney, NSW, Australia
- Sydney Medical School, University of Sydney, Sydney, NSW, Australia
| | - Sanjay Pandanaboyana
- Hepatopancreatobiliary and Transplant Unit, Freeman Hospital, Newcastle Upon Tyne, UK.
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2
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Paolino G, Basturk O, Esposito I, Hong SM, Brosens LA, Tarcan Z, Wood LD, Gkountakos A, Omori Y, Mattiolo P, Ciulla C, Marchegiani G, Pea A, Bevere M, De Robertis R, D'Onofrio M, Salvia R, Cheng L, Furukawa T, Scarpa A, Adsay V, Luchini C. Comprehensive Characterization of Intraductal Oncocytic Papillary Neoplasm of the Pancreas: A Systematic and Critical Review. Mod Pathol 2024; 37:100554. [PMID: 38950698 DOI: 10.1016/j.modpat.2024.100554] [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: 02/08/2024] [Revised: 05/23/2024] [Accepted: 06/20/2024] [Indexed: 07/03/2024]
Abstract
Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a recently recognized pancreatic tumor. Here, we aimed to determine its most essential features with the systematic review tool. PubMed, Scopus, and Embase were searched for studies reporting data on pancreatic IOPN. The clinicopathologic, immunohistochemical, and molecular data were extracted and summarized. Then, a comparative analysis of the molecular alterations of IOPN with those of pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm from reference cohorts (including The Cancer Genome Atlas) was conducted. The key findings from 414 IOPNs were as follows: 1) The male-to-female ratio was 1.5:1. Pancreatic head was the most common site (131/237; 55.3%), but a diffuse tumor extension involving more than one pancreatic segment was described in about 1 out of 5 cases (49/237; 20.6%). The mean size was 45.5 mm. An associated invasive carcinoma was present in 50% of cases (168/336). In those cases, most tumors were pT1 or pT2 and pN0 (>80%), and vascular invasion was uncommon (20.6%). Regarding survival, more than 90% of patients were alive after surgical resection. 2) Immunohistochemical and molecular features were as follows. The most commonly expressed mucins were MUC5AC (110/112; 98.2%) and MUC6 (78/84; 92.8%). Compared with pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasm, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, and GNAS were less altered in IOPN (P < .01). Moreover, fusions involving PRKACA or PRKACB gene were detected in all of the 68 cases examined, with PRKACB::ATP1B1 being the most common (27/68 cases; 39.7%). These genomic events emerged as an entity-defining molecular alteration of IOPN (P < .01). Thus, such fusions represent a promising biomarker for diagnostic purposes. Recent evidence also suggests their role in influencing the acquisition of oncocytic morphology. IOPN is a distinct pancreatic neoplasm with specific clinicopathologic and molecular features. Considering the clinical or prognostic implications, its recognition is essential for pathologists and, ultimately, patients' management.
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Affiliation(s)
- Gaetano Paolino
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; Pathology Unit, Azienda Socio Sanitaria Territoriale Spedali Civili Di Brescia, Brescia, Italy
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Irene Esposito
- Institute of Pathology, University Hospital of Duesseldorf, Duesseldorf, Germany
| | - Seung-Mo Hong
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
| | - Lodewijk A Brosens
- Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Zeynep Tarcan
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Laura D Wood
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Anastasios Gkountakos
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Yuko Omori
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Paola Mattiolo
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Calogero Ciulla
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Giovanni Marchegiani
- Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Antonio Pea
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Michele Bevere
- ARC-Net Research Center, University of Verona, Verona, Italy
| | - Riccardo De Robertis
- Section of Radiology, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy
| | - Mirko D'Onofrio
- Section of Radiology, Department of Diagnostics and Public Health, University and Hospital Trust of Verona, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, The Pancreas Institute, University and Hospital Trust of Verona, Verona, Italy
| | - Liang Cheng
- Department of Pathology and Laboratory Medicine, The Warren Albert Medical School of Brown University, Lifespan Academic Medical Center, and the Legorreta Cancer Center at Brown University, Providence, Rhode Island
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Aldo Scarpa
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; ARC-Net Research Center, University of Verona, Verona, Italy
| | - Volkan Adsay
- Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine, Istanbul, Turkey
| | - Claudio Luchini
- Section of Pathology, Department of Diagnostics and Public Health, University of Verona, Verona, Italy; ARC-Net Research Center, University of Verona, Verona, Italy.
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Gardner TB, Park WG, Allen PJ. Diagnosis and Management of Pancreatic Cysts. Gastroenterology 2024; 167:454-468. [PMID: 38442782 DOI: 10.1053/j.gastro.2024.02.041] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 01/01/2024] [Accepted: 02/18/2024] [Indexed: 03/07/2024]
Abstract
As pancreatic cyst incidence rises, likely due to the ubiquitous increase in cross-sectional imaging, their management presents multiple challenges for both the practitioner and patient. It is critical that all pancreatic cysts are appropriately characterized, as treatment decisions depend on an accurate diagnosis. Diagnostic modalities such as cytology, biopsy, and cyst fluid biomarkers allow for definitive diagnosis of virtually all lesions. Some cysts, such as intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, and cystic pancreatic endocrine neoplasms, have malignant potential and must be surveyed. Other cysts, such as serous cystadenomas and pancreatic fluid collections, do not have malignant potential. Surveillance strategies vary widely depending on cyst type and size and while multiple medical societies advocate surveillance, their published surveillance guidelines are heterogenous. Cysts with high-risk stigmata or worrisome features are usually resected, depending on the patient's surgical fitness. In patients unfit for resection, newer endoscopic ablative techniques are advocated. Controversial aspects regarding cyst management include whether surveillance can be stopped, how surveillance should be performed, and the extensive financial burden cyst management places on the health care system. Further study into the natural history of cystic lesions, including definitive determination of the rate of malignant transformation for each cyst type, is essential.
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Affiliation(s)
- Timothy B Gardner
- Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
| | - Walter G Park
- Section of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Peter J Allen
- Division of Surgical Oncology, Duke University Medical Center, Durham, North Carolina
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4
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Wang Y, Lih TM, Lee JW, Ohtsuka T, Hozaka Y, Mino-Kenudson M, Adsay NV, Luchini C, Scarpa A, Maker AV, Kim GE, Paulino J, Chen L, Jiao L, Sun Z, Goodman D, Pflüger MJ, Roberts NJ, Matthaei H, Wood LD, Furukawa T, Zhang H, Hruban RH. Multi-omic profiling of intraductal papillary neoplasms of the pancreas reveals distinct expression patterns and potential markers of progression. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.07.07.602385. [PMID: 39005476 PMCID: PMC11245086 DOI: 10.1101/2024.07.07.602385] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/16/2024]
Abstract
In order to advance our understanding of precancers in the pancreas, 69 pancreatic intraductal papillary neoplasms (IPNs), including 64 intraductal papillary mucinous neoplasms (IPMNs) and 5 intraductal oncocytic papillary neoplasms (IOPNs), 32 pancreatic cyst fluid samples, 104 invasive pancreatic ductal adenocarcinomas (PDACs), 43 normal adjacent tissues (NATs), and 76 macro-dissected normal pancreatic ducts (NDs) were analyzed by mass spectrometry. A total of 10,246 proteins and 22,284 glycopeptides were identified in all tissue samples, and 756 proteins with more than 1.5-fold increase in abundance in IPMNs relative to NDs were identified, 45% of which were also identified in cyst fluids. The over-expression of selected proteins was validated by immunolabeling. Proteins and glycoproteins overexpressed in IPMNs included those involved in glycan biosynthesis and the immune system. In addition, multiomics clustering identified two subtypes of IPMNs. This study provides a foundation for understanding tumor progression and targets for earlier detection and therapies. Significance This multilevel characterization of intraductal papillary neoplasms of the pancreas provides a foundation for understanding the changes in protein and glycoprotein expression during the progression from normal duct to intraductal papillary neoplasm, and to invasive pancreatic carcinoma, providing a foundation for informed approaches to earlier detection and treatment.
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Vaalavuo Y, Vornanen M, Ahola R, Antila A, Rinta-Kiikka I, Sand J, Laukkarinen J. Long-term (10-year) outcomes and prognostic factors in resected intraductal papillary mucinous neoplasm tumors in Finland: A nationwide retrospective study. Surgery 2023:S0039-6060(23)00059-4. [PMID: 37062604 DOI: 10.1016/j.surg.2023.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 12/21/2022] [Accepted: 02/07/2023] [Indexed: 04/18/2023]
Abstract
BACKGROUND The degree of dysplasia is the most important prognostic factor for patients with resected intraductal papillary mucinous neoplasms. Intraductal papillary mucinous neoplasms are predominantly premalignant conditions; in most cases, surveillance is an adequate treatment. If worrisome features are present, surgery should be considered. However, there is limited data on the long-term prognosis of resected intraductal papillary mucinous neoplasms. We aimed to ascertain the nationwide survival of patients with resected intraductal papillary mucinous neoplasms and identify factors associated with survival. METHODS This is a retrospective nationwide cohort study. All intraductal papillary mucinous neoplasms operated on in Finland between 2000 and 2008 were identified. Patient records were evaluated, and original radiologic data and histologic samples were re-evaluated. Survival data were collected after a 10-year follow-up period. RESULTS Out of 2,024 pancreatic resections, 88 were performed for intraductal papillary mucinous neoplasm. The median age of the patients was 65 years. Histologic diagnoses were main duct intraductal papillary mucinous neoplasm 47/88 (53,4%), mixed-type intraductal papillary mucinous neoplasm 27/88 (30.7%), and branchduct intraductal papillary mucinous neoplasm 14/88 (15.9%). Of the tumors, 40/88 (45.5%) were low-grade dysplasia, 9/88 (10.2%) high-grade, and 39/88 (44.3%) were invasive cancer. The median survival was 121 (range 0-252) months. Ten-year survival was 72.5%, 66.7%, and 23.1% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. Ten-year mortality for pancreatic cancer was 5%, 9.1%, and 71.8% in the low-grade dysplasia, high-grade dysplasia, invasive cancer groups, respectively. CONCLUSION Overall, 44.3% of the patients had a malignant tumor, and three-quarters (74.5%) of the main duct intraductal papillary mucinous neoplasms were malignant or high-grade dysplasia at the time of surgery. Ten-year survival was significantly better in patients operated on at the stage of a premalignant tumor (low-grade dysplasia + high-grade dysplasia) than in patients operated on at the stage of a malignant tumor.
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Affiliation(s)
- Yrjö Vaalavuo
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland
| | - Martine Vornanen
- Department of Pathology, Fimlab Laboratories, Tampere University Hospital, Finland
| | - Reea Ahola
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland
| | - Anne Antila
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland
| | - Irina Rinta-Kiikka
- Faculty of Medicine and Health Technology, Tampere University, Finland; Department of Radiology, Tampere University Hospital, Finland
| | - Juhani Sand
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland
| | - Johanna Laukkarinen
- Department of Gastroenterology and Alimentary Tract Surgery, Tampere University, Finland; Faculty of Medicine and Health Technology, Tampere University, Finland.
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6
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Detlefsen S, Jakobsen M, Nielsen MFB, Klöppel G, Mortensen MB. Expression of CD117, CK17, CK20, MUC4, villin and mismatch repair deficiency in pancreatic intraductal papillary mucinous neoplasm. Pathol Res Pract 2020; 217:153312. [PMID: 33341087 DOI: 10.1016/j.prp.2020.153312] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2020] [Revised: 11/29/2020] [Accepted: 12/01/2020] [Indexed: 12/28/2022]
Abstract
Among pancreatic intraductal papillary neoplasms, gastric, intestinal, and pancreatobiliary intraductal papillary mucinous neoplasm (IPMN), intraductal oncocytic papillary neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN) have been defined, differing regarding association with invasive carcinoma and prognosis. Immunohistochemistry (IHC) can help in the distinction of these neoplasms, but a proportion is unclassifiable using recommended markers. Hence, additional markers useful for the typing of pancreatic intraductal papillary neoplasms are needed. The reported frequencies of the different types of IPMNs in surgical series vary to some extent, and such data based on Danish patients are currently lacking. Besides, the role of mismatch repair (MMR) deficiency in these neoplasms has not been fully elucidated. We aimed to evaluate the frequency of different types of pancreatic intraductal papillary neoplasms in a Danish cohort. Furthermore, we aimed to examine the utility of CD117, CK17, CK20, MUC4, and villin as markers for their distinction, in addition to the recommended markers MUC1, MUC2, MUC5AC, MUC6 and CDX2, and to evaluate the frequency of MMR deficiency. We typed 40 consecutively resected pancreatic intraductal papillary neoplasms according to the WHO criteria from 2019. IHC for CD117, CDX2, CK17, CK20, MLH1, MSH2, MSH6, MUC1 (H23), MUC1 (Ma695), MUC2, MUC4, MUC5AC, MUC6, PMS2, and villin was performed and evaluated using a five-tiered semiquantitative scale. A subset of the tumours was examined with PCR for microsatellite instability (MSI). Most tumours were intestinal (40 %) and gastric (40 %) IPMNs, followed by pancreatobiliary (17 %) IPMNs and IOPN (3 %). All cases were MMR proficient. We found a higher expression of MUC4, CK20 and villin in intestinal compared to gastric IPMNs (p < 0.01, p < 0.001 and p < 0.001). MUC4 was more strongly expressed in intestinal compared to pancreatobiliary IPMNs, while the opposite was found for CK17 (p < 0.05 and p < 0.05). IOPN showed strong CD117 expression (score 4), while all gastric IPMNs were negative and 50 % and 29 % of intestinal and pancreatobiliary IPMNs only showed weak expression (score 1). Our data suggest that CK20, MUC4 and villin may aid in the identification of intestinal IPMNs, while CK17 and CD117 may aid in the identification of pancreatobiliary IPMNs and IOPN, in some cases. However, additional studies evaluating these markers in pancreatic intraductal papillary neoplasms are needed.
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Affiliation(s)
- Sönke Detlefsen
- Department of Pathology, Odense University Hospital, J.B. Winsløws Vej 15, 5000, Odense C, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, J.B. Winsløws Vej 19, 5000, Odense C, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark.
| | - Mark Jakobsen
- Department of Pathology, Odense University Hospital, J.B. Winsløws Vej 15, 5000, Odense C, Denmark
| | - Michael Friberg Bruun Nielsen
- Department of Pathology, Odense University Hospital, J.B. Winsløws Vej 15, 5000, Odense C, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark
| | - Günter Klöppel
- Institute of Pathology, Technical University of Munich, Munich, Germany
| | - Michael Bau Mortensen
- Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, J.B. Winsløws Vej 19, 5000, Odense C, Denmark; Odense Pancreas Center (OPAC), Odense University Hospital, Odense, Denmark; Department of Surgery, HPB Section, Odense University Hospital, J.B. Winsløws Vej 4, 5000, Odense C, Denmark
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7
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Shiihara M, Yamamoto M. Evaluation of preoperative prognostic factors in patients with resectable invasive intraductal papillary mucinous carcinoma. Surgery 2020; 168:994-1002. [PMID: 32139141 DOI: 10.1016/j.surg.2020.01.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/01/2020] [Accepted: 01/16/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Upfront surgery is the standard treatment for resectable invasive intraductal papillary mucinous carcinoma; however, recurrence is common. Therefore, we investigated the recurrence, surgical outcome, and preoperative prognostic factors for recurrence in patients with resectable invasive intraductal papillary mucinous carcinoma. METHODS We analyzed 111 patients who underwent upfront surgery for resectable invasive intraductal papillary mucinous carcinoma between 2000 and 2017 and evaluated the relationship among clinicopathologic factors, recurrence, and outcomes. RESULTS The 5-year recurrence-free survival and disease-specific survival rates were 61% and 74%, respectively. The median time to recurrence was 1.1 years. In multivariate analysis, carbohydrate antigen 19-9 ≥83 U/mL (hazard ratio: 2.8 and 3.1), tumor size ≥2.2 cm (hazard ratio: 3.5 and 4.7), and pathologic tubular adenocarcinoma grade 2 (hazard ratio: 3.1 and 5.2) were risk factors for a shorter recurrence-free survival and disease-specific survival, respectively. Lymph node metastasis (hazard ratio: 3.9) was also a risk factor for a shorter disease-specific survival. When examining outcomes according to preoperatively measurable factors (carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm), the 5-year recurrence rates in patients with none (n = 47), 1 (n = 46), and both (n = 18) risk factors were 17%, 48%, and 78%, respectively. Five-year disease-specific survival rates in patients with none, 1, and both preoperative risk factors were 95%, 69%, and 31%, respectively. CONCLUSION Carbohydrate antigen 19-9 ≥83 U/mL and tumor size ≥2.2 cm were independent preoperative risk factors for poor outcomes in patients with resectable invasive intraductal papillary mucinous carcinoma.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan.
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University Japan
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8
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Taggart MW, Foo WC, Lee SM. Tumors of the Gastrointestinal System Including the Pancreas. ONCOLOGICAL SURGICAL PATHOLOGY 2020:691-870. [DOI: 10.1007/978-3-319-96681-6_12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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9
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Izumo W, Higuchi R, Furukawa T, Yazawa T, Uemura S, Matsunaga Y, Shiihara M, Yamamoto M. Comparison of patients with invasive intraductal papillary mucinous carcinoma and invasive ductal carcinoma of the pancreas: a pathological type- and stage-matched analysis. Scand J Gastroenterol 2019; 54:1412-1418. [PMID: 31680568 DOI: 10.1080/00365521.2019.1684554] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: We compared the pathological features and stage-matched outcomes of patients with invasive intraductal papillary mucinous carcinoma (IPMC) and invasive ductal carcinoma (IDC) of the pancreas to identify the reasons for these diseases' differing prognoses.Methods: We analyzed 114 and 560 patients who underwent curative pancreatectomy for invasive IPMC and IDC, respectively, and analyzed their clinicopathological factors.Results: The disease-specific survival (DSS) of patients with invasive IPMC was significantly superior to that of patients with IDC exhibiting all pathological types at all stages. The DSS of patients with invasive IPMC exhibiting tubular adenocarcinoma was significantly superior to that of their counterparts with IDC only among those with stage IIB (p = .045). When comparing patients with stage IIB tubular adenocarcinoma-type invasive IPMC to their counterparts with IDC, the tumor size (2.6 cm vs. 3.3 cm, p = .010), serum level of carbohydrate antigen 19-9 (253 vs. 474 U/mL, p = .035), number of metastatic lymph nodes (3.1 vs. 4.5, p = .033), vascular invasion rate (14% vs. 41%, p = .0019) and local invasion rate (79% vs. 95%, p = .0045) were lower in the former group. Moreover, the frequency of pathological tubular adenocarcinoma grade 1 was higher in patients with invasive IPMC than in those with IDC (38% vs. 12%, p = .0004) as was the R0 resection rate (90% vs. 65%, p = .0027).Conclusions: In pathological type- and stage-matched analyses, invasive IPMC was associated with a better prognosis than IDC only in patients with stage IIB, as factors governing tumor aggressiveness were milder in the former group than in the latter.
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Affiliation(s)
- Wataru Izumo
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Ryota Higuchi
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Toru Furukawa
- Department of Investigative Pathology, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan
| | - Takehisa Yazawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shuichiro Uemura
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Yutaro Matsunaga
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masahiro Shiihara
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Masakazu Yamamoto
- Department of Surgery, Institute of Gastroenterology, Tokyo Woman's Medical University, Shinjuku-ku, Tokyo, Japan
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10
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Faias S, Pereira L, Luís Â, Chaves P, Cravo M. Genetic testing vs microforceps biopsy in pancreatic cysts: Systematic review and meta-analysis. World J Gastroenterol 2019; 25:3450-3467. [PMID: 31341368 PMCID: PMC6639554 DOI: 10.3748/wjg.v25.i26.3450] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Revised: 04/17/2019] [Accepted: 05/18/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.
AIM To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.
METHODS We performed a literature search in Medline, Scopus, and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts, with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) prior to surgery and surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: 1- benign cysts; 2- mucinous low-risk cysts; 3- high-risk cysts, and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis. We also assessed publication bias, heterogeneity, and study quality.
RESULTS Eight studies, including 1206 patients, of which 203 (17%) referred for surgery who met the inclusion criteria were analyzed in the systematic review, and seven studies were included in the meta-analysis. Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts. Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts, with sensitivities of 0.89 (95%CI: 0.79-0.95) and 0.57 (95%CI: 0.42-0.71), specificities of 0.88 (95%CI: 0.75-0.95) and 0.88 (95%CI: 0.80-0.93) and AUC of 0.9555 and 0.92, respectively. The diagnostic yield was higher in microforceps biopsies than in genetic analysis (0.73 vs 0.54, respectively) but the rates of correctly identified cysts were identical (0.73 with 95%CI: 0.62-0.82 vs 0.71 with 95%CI: 0.49-0.86, respectively).
CONCLUSION Genetic testing and microforceps biopsies are useful second tests, with identical results in benign pancreatic cysts. Genetic analysis performs better for low- and high-risk cysts but has lower diagnostic yield.
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Affiliation(s)
- Sandra Faias
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Luisa Pereira
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Matemática e Aplicações (CMA-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Ângelo Luís
- GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Centro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
| | - Paula Chaves
- Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
- Department of Pathology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
| | - Marília Cravo
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisboa 1099-023, Portugal
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11
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Ciaravino V, D'Onofrio M. Pancreatic Ultrasound: State of the Art. JOURNAL OF ULTRASOUND IN MEDICINE : OFFICIAL JOURNAL OF THE AMERICAN INSTITUTE OF ULTRASOUND IN MEDICINE 2019; 38:1125-1137. [PMID: 30835881 DOI: 10.1002/jum.14978] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2019] [Revised: 02/03/2019] [Accepted: 02/05/2019] [Indexed: 06/09/2023]
Abstract
An ultrasound (US) study is often the first imaging approach in patients with abdominal symptoms or signs related to abdominal diseases, and it is often part of the routine workup. The pancreatic gland, despite its retroperitoneal site, can be efficiently examined with US thanks to advances in US technologies. Nowadays, a pancreatic US study could be considered complete if multiparametric, including the use of Doppler imaging, US elastography, and contrast-enhanced imaging for the study of a pancreatic mass. A complete US examination could contribute to a faster diagnosis, especially if the pancreatic lesion is incidentally detected, addressing second-step imaging modalities correctly.
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Affiliation(s)
| | - Mirko D'Onofrio
- Department of Radiology, G. B. Rossi University Hospital, University of Verona, Verona, Italy
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12
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Klausen P, Kovacevic B, Toxvaerd A, Kalaitzakis E, Karstensen JG, Rift CV, Hansen CP, Storkholm J, Vilmann P, Hasselby JP. Subtyping of intraductal papillary mucinous neoplasms - pitfalls of MUC1 immunohistochemistry. APMIS 2018; 127:27-32. [PMID: 30549137 DOI: 10.1111/apm.12900] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 09/08/2018] [Indexed: 12/18/2022]
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN-lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.
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Affiliation(s)
- Pia Klausen
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - Bojan Kovacevic
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - Anders Toxvaerd
- Department of Pathology, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - Evangelos Kalaitzakis
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - John Gásdal Karstensen
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Herlev, Denmark.,Gastro Unit, Division of Surgery, Copenhagen University Hospital Hvidovre, Herlev, Denmark
| | - Charlotte Vestrup Rift
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, København, Denmark
| | - Carsten Palnaes Hansen
- Department of Gastrointestinal Surgery, Copenhagen University Hospital Rigshospitalet, København, Denmark
| | - Jan Storkholm
- Department of Gastrointestinal Surgery, Copenhagen University Hospital Rigshospitalet, København, Denmark
| | - Peter Vilmann
- Gastro Unit, Division of Endoscopy, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - Jane Preuss Hasselby
- Department of Pathology, Copenhagen University Hospital Rigshospitalet, København, Denmark
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13
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Intraductal Tubulopapillary Neoplasm of the Pancreas: A Clinicopathologic and Immunohistochemical Analysis of 33 Cases. Am J Surg Pathol 2017; 41:313-325. [PMID: 27984235 DOI: 10.1097/pas.0000000000000782] [Citation(s) in RCA: 61] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Intraductal tubulopapillary neoplasm (ITPN) is a relatively recently described member of the pancreatic intraductal neoplasm family. Thus, the literature on its histologic and immunohistochemical features, clinical behavior, and its similarities and differences from other pancreatic neoplasms is limited. Thirty-three cases of ITPN, the largest series to date, were identified. Immunohistochemical labeling for cytokeratins, glycoproteins, pancreatic enzymes, markers for intestinal and neuroendocrine differentiation, and antibodies associated with genetic alterations previously described in pancreatic neoplasms was performed. Clinicopathologic features and survival was assessed. Seventeen patients were female and 14 were male. Mean age was 55 years (range, 25 to 79 y). Median overall tumor size was 4.5 cm (range, 0.5 to 15 cm). Forty-five percent of the tumors occurred in the head, 32% in the body/tail, and 23% showed diffuse involvement. Microscopically, the tumors were characterized by intraductal nodules composed of tightly packed small tubular glands lined by cuboidal cells lacking apparent mucin. Although it was often challenging to determine its extent, invasion was present in 71%. Almost all tumors labeled for CAM5.2, CK7, and CK19; most expressed CA19.9, MUC1, and MUC6. CDX2, MUC2, trypsin, chymotrypsin, chromogranin, and synaptophysin were not expressed. SMAD4 expression was retained in 100%; p16 expression and p53 overexpression was seen in 33% and 27%, respectively. Follow-up information was available for 22 patients (median follow-up, 45 mo; range, 11 to 173 mo). Two patients with invasive carcinoma died of disease at 23 and 41 months, respectively. One patient died of unrelated causes at 49 months. Twelve patients were alive with disease. Seven patients were alive with no evidence of disease. The overall 1-, 3-, and 5-year survival rates were 100% in patients without an invasive component and 100%, 91%, and 71%, respectively, in patients with an invasive component (P=0.7). ITPN is a distinct clinicopathologic entity in the pancreas. Despite the difficulties of determining the extent of invasive carcinoma in many cases, the overall outcome seems to be relatively favorable and substantially better than that of conventional pancreatic ductal adenocarcinoma, even when only the cases with invasive carcinoma are considered.
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14
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Rong Y, Wang D, Xu C, Ji Y, Jin D, Wu W, Xu X, Kuang T, Lou W. Prognostic value of histological subtype in intraductal papillary mucinous neoplasm of the pancreas: A retrospective analysis of outcome from one single center. Medicine (Baltimore) 2017; 96:e6599. [PMID: 28403101 PMCID: PMC5403098 DOI: 10.1097/md.0000000000006599] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
We sought to retrospectively analyze the outcomes of patients with intraductal papillary mucinous neoplasm (IPMN) at our pancreatic surgery center, and to evaluate the prognostic value of histological subtype.The clinical data of 121 IPMNs treated in our center between 2005 and 2014 were retrospectively analyzed. Pathological slides were thoroughly reviewed by 2 specialized pathologists.Of the 121 patients, 48, 57, and 16 had main-duct, branch-duct, and mixed type IPMNs, respectively. Forty-one patients had invasive IPMNs. Histological subtypes consisted of 35 intestinal (28.9%), 56 gastric (46.3%), 29 pancreatobiliary (24.0%), and 1 oncocytic type (0.8%). Histological subtype was associated with radiological type, T stage, and degree of dysplasia (P < .05). No significant difference in overall survival was observed among the 4 histological subtypes, regardless of whether we considered all IPMNs (P = .106), or invasive IPMNs only (P = .828). However, the overall survival was associated with radiological type, T stage, degree of dysplasia, lymph-node status, and nerve invasion. For invasive IPMNs, the overall survival was associated with nerve invasion and lymph-node status; however, the association between nerve invasion and overall survival lost statistical significance after multivariate analysis.Histological subtype had limited prognostic value in patients with IPMNs, and the main prognostic factor for patients with invasive IPMNs was the lymph-node status.
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Affiliation(s)
| | | | - Chen Xu
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuan Ji
- Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China
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15
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Kwak HA, Liu X, Allende DS, Pai RK, Hart J, Xiao SY. Interobserver variability in intraductal papillary mucinous neoplasm subtypes and application of their mucin immunoprofiles. Mod Pathol 2016; 29:977-84. [PMID: 27198568 DOI: 10.1038/modpathol.2016.93] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Revised: 04/15/2016] [Accepted: 04/16/2016] [Indexed: 12/28/2022]
Abstract
Intraductal papillary mucinous neoplasm is considered a precursor lesion to pancreatic adenocarcinoma. These are further classified into four histologic subtypes: gastric, intestinal, pancreatobiliary, and oncocytic. The first aim of this study was to assess the interobserver variability among five gastrointestinal pathologists in diagnosing intraductal papillary mucinous neoplasm subtypes by morphology alone. The second aim of the study was to compare intraductal papillary mucinous neoplasm subtypes, which received consensus diagnoses (≥80% agreement) with their respective mucin immunoprofiles (MUC1, MUC2, MUC5AC, MUC6, and CDX2). A consensus histologic subtype was reached in 58% of cases (29/50) among the five gastrointestinal pathologists. Overall there was moderate agreement (κ=0.41, P<0.01) in subtyping intraductal papillary mucinous neoplasms without the use of immunohistochemistry. The histologic subtype with the best interobserver agreement was intestinal type (κ=0.56, P<0.01) followed by pancreatobiliary, gastric, mixed, and oncocytic types (κ=0.43, P<0.01; κ=0.38, P<0.01; κ=0.17, P<0.01; κ=0.08, P<0.04, respectively). Both kappa values for mixed and oncocytic subtypes were likely artificially low due to the underrepresentation of these subtypes in this study and not a true indication of poor interobserver agreement. Following an intradepartmental consensus meeting between two gastrointestinal pathologists, 68% of cases (34/50) received a consensus intraductal papillary mucinous neoplasm subtype. Sixty-nine percent of cases (11/16) that did not receive a consensus intraductal papillary mucinous neoplasm subtype could be classified based on their respective immunoprofiles. Standardizing the use of immunohistochemistry with a mucin immunopanel (MUC1, MUC2, MUC5AC, and MUC6) may improve the agreement of diagnosing intraductal papillary mucinous neoplasm histologic subtypes.
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Affiliation(s)
- Heewon A Kwak
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Xiuli Liu
- Department of Pathology, University of Florida, Gainesville, FL, USA
| | - Daniela S Allende
- Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Rish K Pai
- Department of Pathology, Mayo Clinic, Scottsdale, AZ, USA
| | - John Hart
- Department of Pathology, University of Chicago, Chicago, IL, USA
| | - Shu-Yuan Xiao
- Department of Pathology, University of Chicago, Chicago, IL, USA
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16
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Intraductal Papillary Mucinous Neoplasms Often Contain Epithelium From Multiple Subtypes and/or Are Unclassifiable. Am J Surg Pathol 2016; 40:44-50. [PMID: 26469398 DOI: 10.1097/pas.0000000000000528] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are subclassified into gastric, intestinal, pancreatobiliary, and oncocytic subtypes based on histologic features. The WHO classification scheme suggests use of immunohistochemical stains to help subtype IPMNs with ambiguous histology. Seventy-two pancreatic IPMN resections between 2008 and 2014 were retrospectively evaluated. Immunohistochemistry for CDX2, MUC2, and MUC5AC was performed on cases where the histologic subtype could not be determined on routine hematoxylin and eosin (H&E) sections. There were 41 gastric (57%), 8 intestinal (11%), 4 pancreatobiliary (6%), and 1 oncocytic (1%) IPMNs. Eighteen (25%) IPMNs were either unclassifiable due ambiguous morphology or contained distinct epithelium from >1 subtype (i.e., "mixed"). Two IPMNs initially unclassifiable strictly by H&E morphology were definitively classified as intestinal after positive immunohistochemical staining with CDX2, MUC2, and MUC5AC. Immunohistochemistry for another 7 IPMNs unclassifiable by H&E did not indicate a clear subtype and often contained discordant results (e.g., discordant CDX2 and MUC2 staining). In our experience, a considerable number of IPMNs are either unclassifiable or contain epithelium from >1 subtype. Furthermore, among those IPMNs initially unclassifiable by H&E morphology, application of immunohistochemical stains to aid in subtyping allow for definite classification in only a small subset of cases. These data, when taken in context with the significant ranges in the reported prevalence of specific histologic subtypes, suggest that accurate IPMN subtyping is poorly reproducible in up to 25% of cases, and in these problematic cases, immunohistochemistry adds little value.
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17
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Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, Bassi C, Salvia R, Malleo G, Paiella S, Wolfgang CL, Matthaei H, Offerhaus GJ, Adham M, Bruno MJ, Reid M, Krasinskas A, Klöppel G, Ohike N, Tajiri T, Jang KT, Roa JC, Allen P, Castillo CFD, Jang JY, Klimstra DS, Hruban RH, Members of the Verona Consensus Meeting, 2013. Pathologic Evaluation and Reporting of Intraductal Papillary Mucinous Neoplasms of the Pancreas and Other Tumoral Intraepithelial Neoplasms of Pancreatobiliary Tract: Recommendations of Verona Consensus Meeting. Ann Surg 2016; 263:162-177. [PMID: 25775066 PMCID: PMC4568174 DOI: 10.1097/sla.0000000000001173] [Citation(s) in RCA: 191] [Impact Index Per Article: 21.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND There are no established guidelines for pathologic diagnosis/reporting of intraductal papillary mucinous neoplasms (IPMNs). DESIGN An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. RESULTS (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c; ≤ 0.5, > 0.5-≤ 1, > 1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intra-biliary/cholecystic). CONCLUSIONS These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms.
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Affiliation(s)
- Volkan Adsay
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
| | - Toru Furukawa
- Department of Pathology, Tokyo Women’s Medical University, Tokyo, Japan
| | - Olca Basturk
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | | | - Claudio Bassi
- Department of Surgery, University of Verona, Verona, Italy
| | - Roberto Salvia
- Department of Surgery, University of Verona, Verona, Italy
| | | | | | - Christopher L. Wolfgang
- Department of Surgery, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Hanno Matthaei
- Department of Surgery, University of Bonn, Bonn, Germany
| | - G. Johan Offerhaus
- Department of Pathology, University Medical Center Utrecht, Utrecht, Netherlands
| | - Mustapha Adham
- Department of Surgery, Edouard Herriot Hospital, HCL, Lyon, France
| | - Marco J. Bruno
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, Netherlands
| | - Michelle Reid
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Alyssa Krasinskas
- Department of Pathology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, GA, USA
| | - Günter Klöppel
- Department of Pathology, Technical University, München, Germany
| | - Nobuyuki Ohike
- Department of Pathology, Showa University Fujigaoka Hospital, Yokohama, Japan
| | - Takuma Tajiri
- Department of Pathology, Tokai University Hachioji Hospital, Tokyo, Japan
| | - Kee-Taek Jang
- Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Juan Carlos Roa
- Department of Pathology, Pontificia Universidad Católica de Chile, Chile
| | - Peter Allen
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, USA
| | | | - Jin-Young Jang
- Department of Surgery, Seoul National University Hospital, Seoul, Korea
| | - David S. Klimstra
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| | - Ralph H. Hruban
- Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins University School of Medicine, Baltimore, USA
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De Robertis R, D'Onofrio M, Crosara S, Dal Corso F, Barbi E, Canestrini S, Mucelli RP. Contrast-enhanced ultrasound of pancreatic tumours. Australas J Ultrasound Med 2015; 17:96-109. [PMID: 28191218 PMCID: PMC5024951 DOI: 10.1002/j.2205-0140.2014.tb00032.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Indication/purpose: To review contrast‐enhanced ultrasound features of the most common pancreatic tumours. Methods: Contrast‐enhanced ultrasound (CEUS) can provide distinctive features of pancreatic tumours that are reported in the present paper, providing radiologic‐pathological correlations and clarifying the main differential diagnosis. Conclusion: Contrast‐enhanced ultrasound plays a well‐established role in the evaluation of pancreatic tumours. When possible, CEUS should be always performed after the initial US diagnosis, in order to improve the accuracy of the first line examination.
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Affiliation(s)
- Riccardo De Robertis
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
| | - Mirko D'Onofrio
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
| | - Stefano Crosara
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
| | - Flavia Dal Corso
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
| | - Emilio Barbi
- Department of Radiology Casa di Cura Pederzoli Via Monte Baldo 24 37019 Peschiera del Garda-Verona Italy
| | - Stefano Canestrini
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
| | - Roberto Pozzi Mucelli
- Department of Radiology, GB Rossi Hospital University of Verona Piazzale L.A. Scuro 10 37134 Verona Italy
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Distinct patterns of peritumoral histological findings in subtypes of intraductal papillary mucinous neoplasms of the pancreas. Ann Diagn Pathol 2015; 19:347-52. [DOI: 10.1016/j.anndiagpath.2015.07.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2015] [Revised: 05/12/2015] [Accepted: 07/11/2015] [Indexed: 12/18/2022]
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Qi X, Zhao X, Su J, Xu M, Zhang W, Sheng H, Li Z, Wang J. Malignant transformation and overall survival of morphological subtypes of intraductal papillary mucinous neoplasms of the pancreas: A network meta-analysis. Eur J Intern Med 2015; 26:652-7. [PMID: 26275457 DOI: 10.1016/j.ejim.2015.07.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/15/2015] [Accepted: 07/19/2015] [Indexed: 01/08/2023]
Abstract
BACKGROUND Emerging evidence suggests the predictive role of morphological subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) of intraductal papillary mucinous neoplasms (IPMNs) in malignant transformation and overall survival. But results of these studies are currently discordant. METHODS A comprehensive literature search in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted for eligible studies. Network meta-analysis using the random-effect model was carried out to detect differences in incidences of invasive IPMNs and hazard ratios from survival curves among four morphological subtypes. RESULTS 19 studies were included in the network comparison. The outcomes showed that pancreatobiliary-type (OR for odds ratio=25.87, 95% CI: 12.11-52.10, compared with gastric-type) and oncocytic-type (OR=18.59, 95% CI: 7.18-42.74) IPMNs had the highest risks of progressing to invasive IPMNs, followed by intestinal-type (OR=5.71, 95% CI: 2.85-10.61) and gastric-type IPMNs. With the gastric type as the baseline, pancreatobiliary-type IPMNs were found to have the worst prognosis (HR for hazard ratio=5.05, 95% CrI: 1.33-13.47) while no significant differences were found for the intestinal type (HR=1.90, 95% CrI: 0.59-4.58) and the oncocytic type (HR=3.29, 95% CrI: 0.75-9.71). CONCLUSION It is suggested that pancreatobiliary-type IPMNs are the most likely to become invasive and are associated with poor prognosis. In contrast, the other three subtypes have similar overall survivals even though the oncocytic- and intestinal-type IPMNs are predisposed to be more invasive than gastric-type IPMNs.
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Affiliation(s)
- Xiaolong Qi
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China; Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA, USA
| | - Xin Zhao
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China
| | - Junlei Su
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Mingxin Xu
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Weifeng Zhang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029 China
| | - Hui Sheng
- Department of Endocrinology, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200072, China
| | - Zhiwei Li
- Department of General Surgery, 302 Hospital of PLA, Beijing 100039, China.
| | - Jiping Wang
- Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA, USA.
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Acute pancreatitis in intraductal papillary mucinous neoplasms: A common predictor of malignant intestinal subtype. Surgery 2015; 158:1219-25. [PMID: 26077509 DOI: 10.1016/j.surg.2015.04.029] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Revised: 04/14/2015] [Accepted: 04/22/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute pancreatitis (AP) is a common presenting symptom of intraductal papillary mucinous neoplasms (IPMN). Our objective was to evaluate the clinical and pathologic features of IPMN that present with AP. We hypothesized that the intestinal epithelial subtype, which produces a highly viscous mucin containing MUC2 glycoprotein, is associated with the development of AP. METHODS We performed a case-control study, evaluating 325 patients with IPMN resected at our institution. Clinicopathologic features were assessed for patients with and without a history of AP and compared between the 2 groups. RESULTS A history of AP was found in 69 patients (21%). Of those, 33 (48%) experienced a single episode, and some patients had as many as 10 distinct attacks. Three patients presented with necrotizing pancreatitis requiring operative debridement. After resection, recurrent AP occurred in only 14%. A history of AP was associated with younger age (61 vs 70, P < .001), main duct involvement (odds ratio [OR] 1.73, 95% confidence interval [95% CI] 1.00-3.01; P = .049), intestinal subtype (OR 4.84, 95% CI 2.71-8.67; P < .001), and high-grade dysplasia (OR 1.82, 95% CI 1.07-3.11; P = .028). On multivariate analysis, AP was an independent predictor of intestinal subtype (OR 4.69, 95% CI 2.48-8.84, P < .001), malignancy (OR 1.97, 95% CI 1.07-3.63, P = .029), and main duct involvement (OR 1.87, 95% CI 1.02-3.43, P = .044). CONCLUSION AP is a frequent presenting symptom of IPMN. These patients are younger and have greater odds of harboring malignant intestinal-type IPMN involving the main pancreatic duct.
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A vascular endothelial growth factor gene polymorphism predicts malignant potential in intraductal papillary mucinous neoplasm. Pancreas 2015; 44:608-14. [PMID: 25875799 DOI: 10.1097/mpa.0000000000000305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES The aim of this study was to evaluate the clinical relevance of vascular endothelial growth factor (VEGF) single nucleotide polymorphisms (SNPs) in intraductal papillary mucinous neoplasms (IPMNs). METHODS A total of 169 IPMN and 108 pancreatic ductal adenocarcinoma patients who underwent curative resection were enrolled, and VEGF +405G/C and -460C/T SNPs were investigated. RESULTS Vascular endothelial growth factor +405C/C was found more frequently in malignant IPMNs compared with +405G/G (odds ratio [OR], 2.7; P = 0.04), and +405C allele was associated with malignant IPMNs compared with +405G (P = 0.055). In branch duct IPMNs, VEGF +405C/C was significantly associated with malignant transformation (CC vs GG: OR, 4.0; P = 0.03; CC vs CG + GG: OR, 3.3; P = 0.04), and there was a trend of VEGF +405C/C associated with malignant transformation of gastric-type IPMNs (CC vs GG: OR, 3.0; P = 0.07). When the survival outcomes were analyzed based on VEGF +405G/C SNPs, however, there was no relationship between VEGF SNPs and overall survival in patients with both IPMNs and pancreatic ductal adenocarcinomas. CONCLUSIONS Vascular endothelial growth factor +405G/C SNP was significantly associated with malignant transformation in IPMNs, especially branch duct and gastric-type IPMNs. Vascular endothelial growth factor +405G/C SNP might be helpful in predicting clinical course in pancreatic disease with potential for malignant transformation.
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Scheiman JM, Hwang JH, Moayyedi P. American gastroenterological association technical review on the diagnosis and management of asymptomatic neoplastic pancreatic cysts. Gastroenterology 2015; 148:824-48.e22. [PMID: 25805376 DOI: 10.1053/j.gastro.2015.01.014] [Citation(s) in RCA: 293] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- James M Scheiman
- Department of Internal Medicine and Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Joo Ha Hwang
- Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington
| | - Paul Moayyedi
- Division of Gastroenterology, Hamilton Health Sciences, Farncombe Family Digestive Health Research Institute, McMaster University Hamilton, Ontario, Canada
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Koh YX, Zheng HL, Chok AY, Tan CS, Wyone W, Lim TKH, Tan DMY, Goh BKP. Systematic review and meta-analysis of the spectrum and outcomes of different histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms. Surgery 2015; 157:496-509. [PMID: 25656693 DOI: 10.1016/j.surg.2014.08.098] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2014] [Revised: 08/05/2014] [Accepted: 08/26/2014] [Indexed: 12/23/2022]
Abstract
BACKGROUND Our aim was to review the available evidence to determine the clinical importance of the histologic subtypes of noninvasive and invasive intraductal papillary mucinous neoplasms (IPMNs) on disease characteristics and overall survival. METHODS We reviewed systematically 14 comparative studies that reported clinicopathologic characteristics and survival of 1,617 patients with IPMN (900 noninvasive and 717 invasive). RESULTS The pancreatobiliary subtype was associated with the greatest likelihood of tumor invasion (67.9%; odds ratio [OR], 2.87; 95% CI, 1.90-4.35), harboring an associated mural nodule (56.6%; OR, 2.92; 95% CI, 1.21-7.04), demonstrating tumor recurrence (46.3%; OR, 3.28; 95% CI, 1.41-7.66) and transformation to tubular adenocarcinoma (81.8%; OR, 92.96; 95% CI, 20.76-416.28) among all subtypes. The gastric subtype was associated with the least likelihood of tumor invasion (10.2%; OR, 0.18; 95% CI, 0.13-0.26), association with main duct IPMN (19.2%; OR, 0.12; 95% CI, 0.06-0.26), and tumor recurrence (9.4%; OR, 0.47; 95% CI, 0.26-0.83) among all subtypes. The intestinal subtype had the greatest likelihood of progressing to colloid carcinoma among all subtypes. Tubular adenocarcinoma was associated with an increased risk of vascular invasion (32.9%; OR, 4.86; 95% CI, 1.96-12.01), perineural invasion (54.5%; OR, 2.30; 95% CI, 1.22-4.34), nodal metastasis (52.4%; OR, 3.31; 95% CI, 1.79-6.14), and a positive margin status (17.3%; OR, 8.45; 95% CI, 1.52-46.83). Tubular adenocarcinoma (hazard ratio [HR], 1.90; 95% CI, 1.36-2.67) had a poorer 5-year overall survival compared with colloid carcinoma and was similar to the survival observed in pancreatic ductal adenocarcinoma (HR, 2.00; 95% CI, 1.59-2.52). CONCLUSION The prognosis of IPMN depends on its pathologic subtype. Subtype identification should be considered an essential component in future guidelines for the management of IPMN.
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Affiliation(s)
- Ye Xin Koh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Hui Li Zheng
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Aik-Yong Chok
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Chuen Seng Tan
- Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Wyiki Wyone
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore
| | - Tony K H Lim
- Department of Pathology, Singapore General Hospital, Singapore
| | - Damien M Y Tan
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Brian K P Goh
- Department of Hepatopancreatobiliary and Transplantation Surgery, Singapore General Hospital, Singapore; Duke-NUS Graduate Medical School, Singapore.
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Klöppel G, Basturk O, Schlitter AM, Konukiewitz B, Esposito I. Intraductal neoplasms of the pancreas. Semin Diagn Pathol 2014; 31:452-466. [DOI: 10.1053/j.semdp.2014.08.005] [Citation(s) in RCA: 72] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Das KK, Xiao H, Geng X, Fernandez-del-Castillo C, Morales-Oyarvide V, Daglilar E, Forcione DG, Bounds BC, Brugge WR, Pitman MB, Mino-Kenudson M, Das KM. mAb Das-1 is specific for high-risk and malignant intraductal papillary mucinous neoplasm (IPMN). Gut 2014; 63:1626-34. [PMID: 24277729 PMCID: PMC5614500 DOI: 10.1136/gutjnl-2013-306219] [Citation(s) in RCA: 48] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes that correlate with histological grades and risks for malignant transformation. mAb Das-1 is a monoclonal antibody against a colonic epithelial phenotype that is reactive to premalignant conditions of the upper GI tract. We sought to assess the ability of mAb Das-1 to identify IPMN with high risk of malignant transformation. DESIGN mAb Das-1 reactivity was evaluated in 94 patients with IPMNs by immunohistochemistry. Lesional fluid from 38 separate patients with IPMN (n=27), low-grade non-mucinous cystic neoplasms (n=7) and pseudocysts (n=4) was analysed by ELISA and western blot. RESULTS Immunohistochemistry-Normal pancreatic ducts were non-reactive and low-grade gastric-type IPMN (IPMN-G) (1/17) and intermediate-grade IPMN-G (1/23) were minimally reactive with mAb Das-1. In contrast, mAb Das-1 reactivity was significantly higher in high-risk/malignant lesions (p<0.0001) including: intestinal-type IPMN with intermediate-grade dysplasia (9/10); high-grade dysplasia of gastric (4/7), intestinal (12/12), oncocytic (2/2) and pancreatobiliary types (2/2); and invasive tubular (8/12), colloid (7/7) and oncocytic (2/2) carcinoma. The sensitivity and specificity of mAb Das-1 for high-risk/malignant IPMNs were 85% and 95%, respectively. Lesional fluid-Samples from low- and intermediate-grade IPMN-G (n=9), and other low-grade/benign non-mucinous lesions demonstrated little reactivity with mAb Das-1. Conversely, cyst fluid from high-risk/malignant IPMNs (n=18) expressed significantly higher reactivity (p<0.0001). The sensitivity and specificity of mAbDas-1 in detecting high-risk/malignant IPMNs were 89% and 100%, respectively. CONCLUSIONS mAb Das-1 reacts with high specificity to tissue and cyst fluid from high-risk/malignant IPMNs and thus may help in preoperative clinical risk stratification.
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Affiliation(s)
- Koushik K Das
- Department of Internal Medicine, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Hong Xiao
- Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Xin Geng
- Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
| | | | - Vicente Morales-Oyarvide
- Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA,Department of Surgery, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Ebubekir Daglilar
- Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - David G Forcione
- Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Brenna C Bounds
- Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - William R Brugge
- Division of Gastroenterology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Martha B Pitman
- Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Mari Mino-Kenudson
- Department of Pathology, Massachusetts General Hospital & Harvard Medical School, Boston, Massachusetts, USA
| | - Kiron M Das
- Division of Gastroenterology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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Castellano-Megías VM, Andrés CID, López-Alonso G, Colina-Ruizdelgado F. Pathological features and diagnosis of intraductal papillary mucinous neoplasm of the pancreas. World J Gastrointest Oncol 2014; 6:311-324. [PMID: 25232456 PMCID: PMC4163729 DOI: 10.4251/wjgo.v6.i9.311] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Revised: 11/07/2013] [Accepted: 12/11/2013] [Indexed: 02/05/2023] Open
Abstract
Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a noninvasive epithelial neoplasm of mucin-producing cells arising in the main duct (MD) and/or branch ducts (BD) of the pancreas. Involved ducts are dilated and filled with neoplastic papillae and mucus in variable intensity. IPMN lacks ovarian-type stroma, unlike mucinous cystic neoplasm, and is defined as a grossly visible entity (≥ 5 mm), unlike pancreatic intraepithelial neoplasm. With the use of high-resolution imaging techniques, very small IPMNs are increasingly being identified. Most IPMNs are solitary and located in the pancreatic head, although 20%-40% are multifocal. Macroscopic classification in MD type, BD type and mixed or combined type reflects biological differences with important prognostic and preoperative clinical management implications. Based on cytoarchitectural atypia, IPMN is classified into low-grade, intermediate-grade and high-grade dysplasia. Based on histological features and mucin (MUC) immunophenotype, IPMNs are classified into gastric, intestinal, pancreatobiliary and oncocytic types. These different phenotypes can be observed together, with the IPMN classified according to the predominant type. Two pathways have been suggested: gastric phenotype corresponds to less aggressive uncommitted cells (MUC1 -, MUC2 -, MUC5AC +, MUC6 +) with the capacity to evolve to intestinal phenotype (intestinal pathway) (MUC1 -, MUC2 +, MUC5AC +, MUC6 - or weak +) or pancreatobiliary /oncocytic phenotypes (pyloropancreatic pathway) (MUC1 +, MUC 2-, MUC5AC +, MUC 6 +) becoming more aggressive. Prognosis of IPMN is excellent but critically worsens when invasive carcinoma arises (about 40% of IPMNs), except in some cases of minimal invasion. The clinical challenge is to establish which IPMNs should be removed because of their higher risk of developing invasive cancer. Once resected, they must be extensively sampled or, much better, submitted in its entirety for microscopic study to completely rule out associated invasive carcinoma.
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Ohtsuki Y, Watanabe R, Kimura M, Nomura K, Maeda T, Kito K, Takeji M, Lee GH, Furihata M. Usefulness of KL-6 in the subtyping of intraductal papillary mucinous neoplasia of the pancreas, including carcinoma, dysplasia, and hyperplasia. Med Mol Morphol 2014; 48:85-91. [PMID: 24908068 DOI: 10.1007/s00795-014-0080-1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 05/12/2014] [Indexed: 12/30/2022]
Abstract
KL-6 is known as a useful serum biomarker of the disease activity in interstitial pneumonias. We investigated its usefulness as a biomarker for subtyping intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. IPMNs are generally divided into 4 subtypes, namely pancreatobiliary (PB), intestinal (INT), gastric (GS), and oncocytic (ONC). Aside from the KL-6 antibody, the MUC1, MUC2, MUC5AC, MUC6, and MIB-1 antibodies were also examined. Eighteen IPMN cases were examined, including 12 cases of intraductal papillary mucinous carcinomas (IPMCs) simultaneously associated with dysplasia (IPMDs) and hyperplasia (IPMHs) and 6 IPMD cases with IPMH. KL-6 antibody was positive in the 8 IPMC cases, corresponding to a MUC2-negative PB subtype, but negative in 4 IPMC cases, corresponding to the INT subtype, which is positive for MUC2. IPMD of moderate-to-severe degree positively stained for the KL-6 antibody in the IPMC cases of the PB subtype but not in those of the INT subtype. The IPMH cases were mostly negative for KL-6, similar to the mild IPMD cases. In the 6 cases of mild IPMD and/or IPMH, KL-6 and MUC2 expressions were mostly negative. In conclusion, the KL-6 antibody is immunohistochemically a good biomarker of the PB subtype of IPMC, but not the INT subtype. Identifying IPMN subtypes based on KL-6 stainability would be useful. Clinicopathological studies with more IPMC cases might be needed for further progress in this field of study.
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Affiliation(s)
- Yuji Ohtsuki
- Division of Pathology, Matsuyama-shimin Hospital, Matsuyama, Ehime, 790-0067, Japan,
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Magnetic resonance cholangiopancreatography with secretin stimulation in the diagnosis of intraductal papillary mucinous neoplasm: a paradigmatic case report. Case Rep Radiol 2014; 2014:820359. [PMID: 24716074 PMCID: PMC3971848 DOI: 10.1155/2014/820359] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Accepted: 01/05/2014] [Indexed: 11/18/2022] Open
Abstract
Context. One of the characteristic findings of intraductal papillary mucinous neoplasms (IPMN) is the presence of a direct communication between the lesion and the ductal pancreatic system and when magnetic resonance cholangiopancreatography (MRCP) shows uncertain findings, it is useful to perform a MRCP after secretin stimulation (MRCP-S) which provides a better visualization of the ductal system. Case Report. We present a case of 51-year-old man in whom, during a CT follow-up for a renal tumour, was found a cystic lesion of the pancreas. To better evaluate the lesion and its suspected communication with the pancreatic system, MR with gadolinium and MRCP and MRCP-S were performed. With the MRCP and MRI it was not possible to identify a clear communication between the cystic lesion and the ductal system. MRCP-S showed an increase in signal intensity of the lesion and its communication with the ductal system, allowing us to classify the cystic lesion as a main duct in intraductal papillary mucinous neoplasm. The patient underwent a surgical duodenal pancreatectomy. The histological result of the specimen confirmed the diagnosis of adenocarcinoma IPMN. Conclusion. In this case MRCP-S has allowed a clearer identification of the cystic lesion allowing a correct diagnosis and treatment.
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Dilated papilla with mucin extrusion is a potential predictor of acute pancreatitis associated with intraductal papillary mucinous neoplasms of pancreas. Pancreatology 2013; 13:615-20. [PMID: 24280579 DOI: 10.1016/j.pan.2013.09.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2013] [Revised: 09/21/2013] [Accepted: 09/21/2013] [Indexed: 02/08/2023]
Abstract
BACKGROUND/OBJECTIVES As intraductal papillary mucinous neoplasm (IPMN) of the pancreas is associated with acute pancreatitis (AP) in some cases, predicting the risk of pancreatitis is as important as predicting the risk of malignancy in IPMN cases. In this study, we attempted to clarify the characteristics of IPMN associated with AP, compared to those of IPMN not associated with AP. METHODS From January 2006 to March 2013, data from 88 patients who underwent surgery for IPMN were retrospectively investigated and analyzed. We evaluated clinical and pathological variables of each patient and compared patients with IPMN with AP to those without AP. Furthermore, we presented representative cases of mild and severe pancreatitis caused by IPMN. RESULTS Overall, 12 of 88 patients with IPMN (13.6%) had AP. Seven of the 12 patients had a single episode of AP, whereas the remaining 5 patients were diagnosed with IPMN with repeated AP. Ten of 12 patients with AP were diagnosed with mild AP and the remaining 2 with severe AP. Regarding clinical findings, the proportion of dilated papilla with mucin extrusion was significantly higher in patients with IPMN with AP than in those without AP (p = 0.035). Histological findings indicated that the proportion of intestinal-subtype IPMN was significantly higher in patients with IPMN with AP (p = 0.013). CONCLUSIONS AP caused by IPMN derives mostly from intestinal IPMN. Dilated papilla with mucin extrusion can be a potential predictor of AP.
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Evaluation of clinical meaning of histological subtypes of intraductal papillary mucinous neoplasm of the pancreas. Pancreas 2013; 42:959-66. [PMID: 23462330 DOI: 10.1097/mpa.0b013e31827cddbc] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVES Prognostic value of histological subtypes of pancreatic intraductal papillary mucinous neoplasm (IPMN) has been reported to have conflicting results. The authors investigated the clinicopathological characteristics and prognostic significance of the histological subtypes of IPMNs with various degrees of dysplasia. METHODS Two hundred thirteen patients with surgically treated pancreatic IPMN at a single tertiary care referral center were included. Pathological slides were thoroughly reviewed by a specialized pathologist. RESULTS Of the 213 patients, 38 low-grade, 97 intermediate-grade, and 18 high-grade dysplasia and 59 IPMNs with an associated invasive carcinoma (invasive IPMN) were identified. Histological subtypes consisted of 135 gastric (63.4%), 38 intestinal (17.8%), 38 pancreatobiliary (17.8%), and 2 oncocytic types (0.9%). Histological subtypes were associated with radiological type (P < 0.001), degree of dysplasia (P < 0.001), and T stage (P < 0.001). The proportions of invasive IPMN were 14.1%, 42.1%, 57.9%, and 100% of gastric, intestinal, pancreatobiliary, and oncocytic types, respectively. Disease-specific survival was not affected by histological subtype in overall patients (P = 0.881). For invasive IPMNs, histological subtypes had a marginal significance on survival (P = 0.050), which lost statistical significance after multivariate analysis (P = 0.341). CONCLUSIONS Although histological subtypes are associated with the degree of dysplasia, histological subtypes have limited prognostic value for pancreatic IPMNs.
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Larghi A, Panic N, Capurso G, Leoncini E, Arzani D, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, Zerbi A, Manta R, Fabbri C, Ventrucci M, Tarantino I, Piciucchi M, Carnuccio A, Boggi U, Costamagna G, Delle Fave G, Pezzilli R, Bassi C, Bulajic M, Ricciardi W, Boccia S. Prevalence and risk factors of extrapancreatic malignancies in a large cohort of patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Oncol 2013; 24:1907-1911. [PMID: 23676419 DOI: 10.1093/annonc/mdt184] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The objectives of this study are to estimate prevalence and incidence of extrapancreatic malignancies (EPMs) among intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, and to identify risk factors for their occurrence. PATIENTS AND METHODS We conducted multicentric cohort study in Italy from January 2010 to January 2011 including 390 IPMN cases. EPMs were grouped as previous, synchronous (both prevalent) and metachronous (incident). We calculated the observed/expected (O/E) ratio of prevalent EPMs, and compared the distribution of demographic, medical history and lifestyle habits. RESULTS Ninety-seven EPMs were diagnosed in 92 patients (23.6%), among them 78 (80.4%) were previous, 14 (14.4%) were synchronous and 5 (5.2%) were metachronous. O/E ratios for prevalent EPMs were significantly increased for colorectal carcinoma (2.26; CI 95% 1.17-3.96), renal cell carcinoma (6.00; CI 95% 2.74-11.39) and thyroid carcinoma (5.56; CI 95% 1.80-12.96). Increased age, heavy cigarette smoking, alcohol consumption and first-degree family history of gastric cancer are significant risk factors for EPMs, while first-degree family history of colorectal carcinoma was borderline. CONCLUSION We report an increased prevalence of EPMs in Italian patients with IPMN, especially for colorectal carcinoma, renal cell and thyroid cancers. A systematic surveillance of IPMN cases for such cancer types would be advised.
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Affiliation(s)
| | - N Panic
- Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy; Faculty of Medicine, University of Belgrade, Belgrade; University Clinical-Hospital Center 'Dr Dragisa Misovic-Dedinje', Belgrade, Serbia
| | - G Capurso
- Digestive and Liver Disease Unit, University 'Sapienza', Rome
| | - E Leoncini
- Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - D Arzani
- Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - R Salvia
- Department of Surgery, University of Verona, Verona
| | | | - L Frulloni
- Department of Gastroenterology, University of Verona, Verona
| | - P G Arcidiacono
- Department of Gastroenterology & Gastrointestinal Endoscopy, San Raffaele Hospital, Milano
| | - A Zerbi
- Pancreatic Surgery Section, Istituto Humanitas, Milano
| | - R Manta
- Department of Gastroenterology, S. Agostino Hospital, Modena
| | - C Fabbri
- Department of Gastroenterology, Bellaria Maggiore Hospita, Bologna
| | - M Ventrucci
- Department of Internal Medicine, University of Bologna, Bologna
| | | | - M Piciucchi
- Digestive and Liver Disease Unit, University 'Sapienza', Rome
| | | | - U Boggi
- Department of Surgery, University of Pisa, Pisa
| | | | - G Delle Fave
- Digestive and Liver Disease Unit, University 'Sapienza', Rome
| | - R Pezzilli
- Department of Internal Medicine, University of Bologna, Bologna
| | - C Bassi
- Department of Surgery, University of Verona, Verona
| | - M Bulajic
- Faculty of Medicine, University of Belgrade, Belgrade; University Clinical-Hospital Center 'Dr Dragisa Misovic-Dedinje', Belgrade, Serbia; Department of Gastroenterology, University Clinical Hospital 'Santa Maria della Misericordia', Udine
| | - W Ricciardi
- Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
| | - S Boccia
- Department of Public Health, Università Cattolica del Sacro Cuore, Rome, Italy; IRCCS San Raffaele Pisana, Rome, Italy.
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Preoperative Histological Subtype Classification of Intraductal Papillary Mucinous Neoplasms (IPMN) by Pancreatic Juice Cytology With MUC Stain. Ann Surg 2013; 257:1103-11. [DOI: 10.1097/sla.0b013e318281b824] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Abstract
On abdominal CT scans asymptomatic cystic lesions of the pancreas are accidentally detected in 1-2% of patients. Congenital cysts and pancreatic pseudocysts account for two thirds of these lesions. Pancreatic pseudocysts are a frequent complication of acute and chronic pancreatitis. Among resected cystic neoplasms serous cystic adenoma accounts for 30%, mucinous cystic neoplasms for 45% and intraductal papillary mucinous neoplasms for 25%. The diagnosis of a cystic pancreatic lesion is usually made by diagnostic imaging. Symptomatic lesions require definitive therapeutic treatment after appropriate diagnostic work-up. In the diagnosis of asymptomatic cystic lesions several factors are important, among them whether the cyst is connected to the pancreatic duct (as in IPMN and pseudocysts), the size of lesion (for treatment indications) and whether nodules form in the wall of the cyst (a sign of potential malignancy). EUS-guided fine needle aspiration of the cyst fluid adds to the discrimination between benign, premalignant and malignant cystic lesions. Measuring lipase activity, CEA, viscosity and mucin as well as cytology can help in differentiating cystic lesions. An algorithm is discussed for the differential diagnosis and for selection of the appropriate treatment for pancreatic cystic lesions, most of which never require surgery.
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Nakanishi Y, Nakanuma Y, Ohara M, Iwao T, Kimura N, Ishidate T, Kijima H. Intraductal papillary neoplasm arising from peribiliary glands connecting with the inferior branch of the bile duct of the anterior segment of the liver. Pathol Int 2012; 61:773-7. [PMID: 22126388 DOI: 10.1111/j.1440-1827.2011.02738.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Intraductal papillary neoplasms of the bile duct are generally thought to arise from neoplastic papillary proliferation of epithelial cells lining the bile duct. We herein report a case with findings that strongly suggested that the biliary cystic tumor might have derived from a peribiliary gland. A 69-year-old female was found to have a cystic lesion with intracystic protrusions at the anterior segment of the right hepatic lobe and underwent hepatic anterior segment resection. Fluoroscopy of the resected specimen injected with contrast medium into the cyst revealed a connection between the cystic lesion and the bile ducts. The cyst was multilocular in appearance. On microscopic examination, the cyst was located within the portal tract of the inferior branch of the anterior segment and connected with the inferior branch of the bile duct. The wall of the hepatic cyst lacked an ovarian-like stroma. The tumor was composed of papillary and glandular components, and the tumor cells were similar to gastric foveolar and pyloric gland epithelia and regarded as adenoma. These tumor cells were positive for MUC 5AC, MUC6, and HIK1083. The tumor was finally diagnosed as an intraductal papillary neoplasm of the bile duct (adenoma, gastric type) arising from a peribiliary gland.
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Affiliation(s)
- Yoshitsugu Nakanishi
- Department of Surgery, National Hospital Organization, Hakodate Hospital, Hakodate, Japan.
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Yang J, Wang W, Yan L. The clinicopathological features of intraductal papillary neoplasms of the bile duct in a Chinese population. Dig Liver Dis 2012; 44:251-6. [PMID: 21930444 DOI: 10.1016/j.dld.2011.08.014] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Revised: 08/10/2011] [Accepted: 08/15/2011] [Indexed: 02/05/2023]
Abstract
BACKGROUND Intraductal papillary neoplasms of the bile duct have been applied to certain types of papillary tumours occurring in the biliary tract. Although many cases have been sporadically reported, there remain controversies. AIMS To analyze the clinicopathologic characteristics and long-term survival of intraductal papillary neoplasms of the bile duct. METHODS The clinicopathologic data of 52 patients who underwent surgery for intraductal papillary neoplasms of the bile duct were retrospectively evaluated. RESULTS In our series, tumours located in intrahepatic and hilar bile duct, rather than in extrahepatic bile duct, were more commonly diagnosed as adenomas or borderline tumours (12/19 and 7/13 vs 6/20; P=0.046). And the gastric type was more commonly associated with adenomas or borderline tumour (85.7%), whilst the pancreaticobiliary type mainly comprised of noninvasive carcinoma or invasive carcinoma (93.8%). However, only the types of treatment (median survival: curative resection: 72 months and palliative groups: 12 months; P<0.001) and histologic grades (adenoma or borderline malignancy vs noninvasive carcinoma: P=0.018) were significantly associated with survival. CONCLUSION Intraductal papillary neoplasms of the bile duct are rare type of biliary neoplasms, long-term survival may be achieved with complete resection. However, further studies are needed to clarify the relationship between these variables like location, cellular types and histologic grades.
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Affiliation(s)
- Jian Yang
- Division of Liver Transplantation, West China Hospital, West China School of Medicine, Sichuan University, 37# Guoxue Lane, Chengdu 610041, China
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38
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Matsuda Y, Hagio M, Naito Z, Ishiwata T. Clinicopathological Features of 30 Autopsy Cases of Pancreatic Carcinoma. J NIPPON MED SCH 2012; 79:459-67. [DOI: 10.1272/jnms.79.459] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Affiliation(s)
- Yoko Matsuda
- Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School
| | - Masahito Hagio
- Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School
| | - Zenya Naito
- Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School
| | - Toshiyuki Ishiwata
- Departments of Pathology and Integrative Oncological Pathology, Nippon Medical School
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Kim KM, Lee JK, Shin JU, Lee KH, Lee KT, Sung JY, Jang KT, Heo JS, Choi SH, Choi DW, Lim JH. Clinicopathologic features of intraductal papillary neoplasm of the bile duct according to histologic subtype. Am J Gastroenterol 2012; 107:118-125. [PMID: 21946282 DOI: 10.1038/ajg.2011.316] [Citation(s) in RCA: 80] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES Despite an increase in the reports of intraductal papillary neoplasm of the bile duct (IPN-B), the clinical characteristics and long-term prognosis of this disease are not well known compared with those of intraductal papillary mucinous neoplasms of the pancreas. The objective of our study was to compare the clinical features, radiologic findings, and clinical outcomes of IPN-B according to histologic subtype. METHODS A retrospective analysis was performed on the medical records of 97 patients diagnosed with IPN-B by pathologic analysis of their surgical specimens between May 1995 and May 2010. We compared the clinical manifestations, radiological findings, pathologic grade, curative resection rate, recurrence, and overall survival according to four histologic subtypes: gastric (n=15), intestinal (n=46), pancreaticobiliary (n=33), and oncocytic (n=3), which were classified on the basis of hematoxylin and eosin staining and the immunohistochemical profile of mucin core proteins. RESULTS Mucin hypersecretion was significantly more frequent in patients with gastric and intestinal types than it was in those with oncocytic and pancreaticobiliary types (P=0.014). There were no significant differences between groups regarding the presence of bile duct stones or tumor location. The frequency of invasive carcinoma in the pancreaticobiliary type was significantly higher than those in the gastric and intestinal types (72.7 vs. 26.7 and 32.6%, P<0.001 and P<0.001). When comparing the survival curves according to histologic subtype, patients with pancreaticobiliary type demonstrated significantly worse survival compared to those with gastric and intestinal types (P=0.035). CONCLUSIONS Gastric and intestinal types of IPN-B have similar clinical characteristics compared with the pancreaticobiliary type, which has a worse prognosis.
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Affiliation(s)
- Kwang Min Kim
- Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
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40
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Sclabas GM, Barton JG, Smyrk TC, Barrett DA, Khan S, Kendrick ML, Reid-Lombardo KM, Donohue JH, Nagorney DM, Que FG. Frequency of subtypes of biliary intraductal papillary mucinous neoplasm and their MUC1, MUC2, and DPC4 expression patterns differ from pancreatic intraductal papillary mucinous neoplasm. J Am Coll Surg 2011; 214:27-32. [PMID: 22112419 DOI: 10.1016/j.jamcollsurg.2011.09.025] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2011] [Revised: 09/27/2011] [Accepted: 09/30/2011] [Indexed: 12/13/2022]
Abstract
BACKGROUND Biliary intraductal papillary mucinous neoplasm (B-IPMN) has been proposed as a unique clinicopathologic disease with distinct histopathologic features, although wide acceptance remains controversial. A recent consensus conference classified pancreatic IPMN (P-IPMN) into 4 subtypes (ie, gastric, intestinal, pancreatobiliary, oncocytic) based on morphologic appearance and mucin (MUC) staining properties. The aim of this study was to determine whether B-IPMN has similar histopathologic and immunologic subtypes to P-IPMN. STUDY DESIGN Specific immunostaining for MUC1, MUC2, and deleted for pancreas cancer, locus 4 were performed on specimens from 19 patients with a histopathologic diagnosis of B-IPMN. Immunostaining patterns of B-IPMN were correlated with histopathology. RESULTS Based on histopathology, the following subtypes of B-IPMN were identified: pancreatobiliary n = 9 (47%), intestinal n = 8 (42%), oncocytic n = 2 (11%), and gastric n = 0 (0%). Pancreatobiliary and oncocytic subtypes of B-IPMN were positive for MUC1 and negative for MUC2, and intestinal subtypes were positive for MUC2 and negative for MUC1. Thirteen of the 19 B-IPMN were associated with invasive carcinoma; loss of deleted for pancreas cancer, locus 4 was found in 6 of 13 invasive components and in 3 of 19 noninvasive components of B-IPMN. Five-year survival for patients with resected B-IPMN and invasive carcinoma was 38%, which is similar to that for resected P-IPMN with invasive carcinoma. CONCLUSIONS Histopathologic subtypes and type-specific MUC expression patterns of B-IPMN resemble those of P-IPMN. MUC1 expression and/or absence of MUC2 expression, which correlate with aggressive features of P-IPMN, were found in B-IPMN and correlate with invasive B-IPMN. Loss of deleted for pancreas cancer, locus 4 parallels the findings observed in P-IPMN. These findings provide additional support that B-IPMN is a unique entity with similarities to main duct P-IPMN.
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Affiliation(s)
- Guido M Sclabas
- Division of Gastroenterologic and General Surgery, Mayo Clinic, Rochester, MN 55905, USA
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41
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Abstract
Intraductal papillary mucinous neoplasm (IPMN) is a grossly visible (≥1 cm), mucin-producing neoplasm that arises in the main pancreatic duct and/or its branches. Patients with intraductal papillary mucinous neoplasm can present with symptoms caused by obstruction of the pancreatic duct system, or they can be asymptomatic. There are 3 clinical subtypes of intraductal papillary mucinous neoplasm: main duct, branch duct, and mixed. Five histologic types of intraductal papillary mucinous neoplasm are recognized: gastric foveolar type, intestinal type, pancreatobiliary type, intraductal oncocytic papillary neoplasm, and intraductal tubulopapillary neoplasm. Noninvasive intraductal papillary mucinous neoplasms are classified into 3 grades based on the degree of cytoarchitectural atypia: low-, intermediate-, and high-grade dysplasia. The most important prognosticator, however, is the presence or absence of an associated invasive carcinoma. Some main duct-intraductal papillary mucinous neoplasms progress into invasive carcinoma, mainly tubular adenocarcinoma (conventional pancreatic ductal adenocarcinoma) and colloid carcinoma. Branch duct-intraductal papillary mucinous neoplasms have a low risk for malignant transformation. Preoperative prediction of the malignant potential of an intraductal papillary mucinous neoplasm is of growing importance because pancreatic surgery has its complications, and many small intraductal papillary mucinous neoplasms, especially branch duct-intraductal papillary mucinous neoplasms, have an extremely low risk of progressing to an invasive cancer. Although most clinical decision making relies on imaging, a better understanding of the molecular genetics of intraductal papillary mucinous neoplasm could help identify molecular markers of high-risk lesions. When surgery is performed, intraoperative frozen section assessment of the pancreatic resection margin can guide the extent of resection. Intraductal papillary mucinous neoplasms are often multifocal, and surgically resected patients should be followed for metachronous disease.
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42
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Xiao HD, Yamaguchi H, Dias-Santagata D, Kuboki Y, Akhavanfard S, Hatori T, Yamamoto M, Shiratori K, Kobayashi M, Shimizu M, Fernandez-Del Castillo C, Mino-Kenudson M, Furukawa T. Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms. J Pathol 2011; 224:508-16. [PMID: 21547907 DOI: 10.1002/path.2875] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2010] [Revised: 02/06/2011] [Accepted: 02/11/2011] [Indexed: 12/27/2022]
Abstract
Intraductal papillary mucinous neoplasm (IPMN) consists of four epithelial subtypes. Of those, pancreatobiliary and oncocytic types are recently recognized and relatively uncommon, and usually exhibit high-grade dysplasia. The biological properties and molecular characteristics of these two types have not been well documented. The few molecular studies of the oncocytic type showed absence of KRAS mutations commonly seen in the other subtypes, raising the possibility that the oncocytic type is distinct from the other subtypes. Thus, we examined clinicopathological features and molecular alterations of the two subtypes. The study cohort consisted of 12 pancreatobiliary and 18 oncocytic IPMN cases. KRAS, BRAF, and PIK3CA mutations and TP53, SMAD4, and β-catenin expression were analysed, and the results of molecular and clinicopathological profiles were compared between the two subtypes. KRAS mutations were identified in the oncocytic type, but less frequently than the pancreatobiliary type (17% versus 58%, p = 0.048). BRAF mutation was found in a single oncocytic tumour, and no PIK3CA mutations were seen in any of the study cohort. TP53 overexpression was less frequent in the oncocytic type than in the pancreatobiliary type (11% versus 58%, p = 0.013). Invasive components were present in 50% of the oncocytic and 92% of the pancreatobiliary types, with lymph node metastasis more frequently seen in the latter, corresponding to better outcomes in the former (5-year survival rates: 93% versus 32%, p = 0.014). Our demonstration of KRAS and BRAF mutations in the oncocytic-type IPMN supports a role for the activation of the RAS-MAPK pathway in this tumour type. However, the less frequent TP53 overexpression associated with the significantly lower rates of invasion and nodal disease in the oncocytic type correlates with better outcomes compared to the pancreatobiliary type.
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Affiliation(s)
- Hong D Xiao
- Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, USA
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Localization of the most severely dysplastic/invasive lesions and mucin phenotypes in intraductal papillary mucinous neoplasm of the pancreas. Pancreas 2011; 40:588-94. [PMID: 21441843 DOI: 10.1097/mpa.0b013e31820d1a03] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The aim of this study was to define the relevance of mural nodules (MNs) as a "direct" indicator of malignancy of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. METHODS Thirty-nine surgically resected IPMNs excluding obviously invasive carcinomas were examined. The distribution of the most severely dysplastic lesions was mapped on specimens. Immunohistochemical analysis for MUC1 and MUC2 was performed on sections containing the histologically predominant lesions and the most severely dysplastic areas. RESULTS The presence of MNs correlated well with the histological grade of IPMN (P < 0.01); however, the most severely dysplastic lesions were associated with a flat/nonelevated area rather than MNs (78.9%). In the MUC1-positive subgroup, minimally invasive carcinoma was colocalized to MNs, whereas most severely dysplastic foci including minimally invasive carcinoma with components of mucinous and tubular adenocarcinoma were observed in the areas apart from MNs in the MUC2-positive and MUC1/2-negative subgroups, respectively. CONCLUSIONS Although our data support the concept that MNs represent areas of higher-grade dysplasia within IPMN, development of invasive lesions from MNs may be limited to cases that are MUC1-positive. Careful attention should be paid to the emergence of invasive IPMN from flat foci in MUC2-positive and MUC1/2-negative cases.
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Abstract
Although considerable progress has been made in our understanding of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, some issues still remain to be resolved. Uncertainty exists regarding the classification of IPMNs. The necessity of the mixed-type category of IPMN and whether such lesions should be defined radiographically or histologically needs to be determined. The preoperative distinction of branch duct IPMNs from nonmucinous cysts should be further investigated so that potentially malignant lesions can be identified and management strategies guided effectively. The role and safety of cystic fluid analysis remains to be clarified in this context. With regard to the diagnosis of malignancy in branch duct IPMNs, criteria for identifying malignancy need to be re-evaluated. The presence of mural nodules is a very reliable predictor; however, controversy exists over the value of size as a reliable indicator. Criteria with increased specificity are needed, perhaps including histological subtype of lesion, to reduce the false-positive rate of the present criteria. Finally, the best modality and interval for surveillance of branch duct IPMNs requires determination because of its significance in terms of malignant transformation, development of distinct ductal adenocarcinoma and disease recurrence after resection.
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Affiliation(s)
- Masao Tanaka
- Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
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45
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Nakanuma Y. A novel approach to biliary tract pathology based on similarities to pancreatic counterparts: is the biliary tract an incomplete pancreas? Pathol Int 2010; 60:419-29. [PMID: 20518896 DOI: 10.1111/j.1440-1827.2010.02543.x] [Citation(s) in RCA: 141] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
There are peribiliary glands around the biliary tract, and these glands drain into the bile duct lumen. Interestingly, small amounts of pancreatic exocrine acini are intermingled with these glands. Experimental studies using animals suggest that the biliary tract shows some potential for pancreatic differentiation. It is noteworth that the biliary tract and pancreas have similar pathological features. IgG4-related sclerosing cholangitis and autoimmune pancreatitis are representative inflammatory diseases with similar features. Intraductal papillary neoplasms are found in the biliary tract and also in the pancreas: intraductal papillary neoplasm of the bile duct (IPNB) and intraductal papillary mucinous neoplasm of the pancreas (IPMN). IPNB and IPMN share common histologic and phenotypic features and biological behaviors. Interestingly, mucinous cystic neoplasm (MCN) arises in both the pancreas and the hepatobiliary system. Intraductal tubular neoplasia is found in both the biliary tract and pancreas as well. Intraepithelial neoplasm is found in the biliary tract and pancreas: biliary intraepithelial neoplasm (BilIN) and pancreatic intraepithelial neoplasm (PanIN). BilIN and PanIN are followed by conventional invasive adenocarcinoma, while IPNB and IPMN are followed by tubular adenocarcinoma and mucinous carcinoma in both organs. Further study of the biliary tract's pathophysiology based on its similarity to pancreatic counterparts is warranted.
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Affiliation(s)
- Yasuni Nakanuma
- Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
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46
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Malignant potential of intraductal papillary mucinous neoplasms of the pancreas. Surg Today 2010; 40:816-24. [PMID: 20740343 DOI: 10.1007/s00595-009-4227-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2009] [Accepted: 05/28/2009] [Indexed: 12/16/2022]
Abstract
An intraductal papillary mucinous neoplasm (IPMN) is now a well-recognized disease entity. In general, the prognosis of IPMN is much more favorable than that of pancreatic ductal adenocarcinoma (PDAC). However, IPMN has a broad biological spectrum and it sometimes progresses, slowly showing neoplastic transformations. International consensus guidelines have been recently proposed for the management of IPMN. While they significantly contribute to appropriate management of IPMN, various issues including the natural history and malignant potential of IPMN are not fully elucidated. This review focuses on the malignant potential, including the postoperative recurrence of IPMN, coincidence of IPMN with PDAC, and extrapancreatic malignancy that may affect the long-term survival of the patients rather than IPMN itself.
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47
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Intraductal papillary-mucinous neoplasms of the gastric and intestinal types may have less malignant potential than the pancreatobiliary type. Pancreas 2010; 39:604-10. [PMID: 20124938 DOI: 10.1097/mpa.0b013e3181c6947a] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are classified into 4 types--gastric, intestinal, pancreatobiliary, and oncocytic--on the basis of their morphology and immunohistochemistry. We classified IPMNs at our institute and used this classification to determine the clinicopathological features, prognosis, and malignant potential of the 4 types. METHODS Sixty-one patients with IPMN who underwent surgery between 2000 and 2007 were evaluated retrospectively. RESULTS There were 24 tumors of the gastric type, 22 intestinal, 12 pancreatobiliary, and 3 oncocytic. Patients with the intestinal or gastric type had a better prognosis than those with the pancreatobiliary type. The intestinal and pancreatobiliary types had almost the same frequencies of carcinoma, but the intestinal type tended to have a lower frequency of invasive carcinoma than the pancreatobiliary type. Patients with invasive carcinomas derived from intestinal-type IPMNs tended to have a better prognosis than those whose invasive carcinomas were derived from the pancreatobiliary type. CONCLUSIONS Intraductal papillary-mucinous neoplasm of the gastric and intestinal types may have less malignant potential than that of the pancreatobiliary type. Invasive carcinomas derived from intestinal-type IPMNs may be less invasive and slower growing than those derived from the pancreatobiliary type.
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Okada KI, Hirabayashi K, Imaizumi T, Matsuyama M, Yazawa N, Dowaki S, Tobita K, Ohtani Y, Tanaka M, Inokuchi S, Makuuchi H. Stromal thrombospondin-1 expression is a prognostic indicator and a new marker of invasiveness in intraductal papillary-mucinous neoplasm of the pancreas. ACTA ACUST UNITED AC 2010; 31:13-9. [PMID: 20203415 DOI: 10.2220/biomedres.31.13] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The invasion of intraductal papillary-mucinous neoplasm (IPMN) is sometimes difficult to diagnose using only ordinary hematoxylin-eosin sections. The aim of this study was to evaluate the invasion of IPMN more precisely using thrombospondin-1 (TSP1) immunohistochemistry as a useful adjunct to morphological examination. Eighty patients that underwent primary resection for pancreatic IPMNs were retrospectively analyzed. The 80 IPMNs were studied for the expression of TSP1, MUC1-CORE, MUC2, and MUC5AC. The cases were evaluated for dysplasia, the presence of invasion, hisological subtypes, and survival. The 80 IPMNs were classified into 29 intraductal papillary-mucinous adenomas (IPMAs), 10 borderline IPMNs, 18 noninvasive intraductal papillary-mucinous carcinomas (IPMCs), and 23 invasive IPMCs according to the WHO classification. Invasive IPMCs were further divided into 12 minimally invasive IPMCs (MI-IPMCs) and 11 invasive carcinomas originating from IPMCs (IC-IPMCs) according to the Japan Pancreatic Society classification. The rate of strongly positive cases with more than 30% of the cancer stroma area expressing TSP1 was significantly higher in MI-IPMC and IC-IPMC than in noninvasive IPMC (P = 0.035, 0.005). Furthermore, patients in the strongly positive group had a significantly poorer prognosis compared to patients in the negative-weakly positive group (P = 0.008, log-rank test). Of the 80 tumors, 22 were classified into gastric-, 45 into intestinal-, 7 into pancreatobiliary-, and 6 into oncocytic-type IPMNs according to criteria described previously. The cases with a strongly positive expression of TSP1 were frequently detected in the pancreatobiliary and oncocytic types (P = 0.001). In conclusion, stromal TSP1 expression is a prognostic indicator and a new marker of invasiveness in IPMN.
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Affiliation(s)
- Ken-Ichi Okada
- Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
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Augustin T, Vandermeer TJ. Intraductal papillary mucinous neoplasm: a clinicopathologic review. Surg Clin North Am 2010; 90:377-98. [PMID: 20362793 DOI: 10.1016/j.suc.2009.12.008] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Intraductal papillary mucinous neoplasm (IPMN) is an intraductal mucin-producing epithelial neoplasm that arises from the main pancreatic duct (MD-IPMN), secondary branch ducts (BD-IPMN), or both (mixed type; Mix-IPMN). Neoplastic progression from benign adenoma to invasive adenocarcinoma has not been proven but is generally thought to occur. With increasing recognition of IPMN, our understanding of the diagnosis and management of the tumors is evolving. At present, treatment options for patients with IPMN range from observation to pancreatic resection depending on the natural history of the lesion. This review focuses on currently available data that guide management decisions for patients with IPMN.
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MESH Headings
- Adenocarcinoma, Mucinous/diagnosis
- Adenocarcinoma, Mucinous/genetics
- Adenocarcinoma, Mucinous/metabolism
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/surgery
- Algorithms
- Biopsy, Fine-Needle/methods
- Carcinoma, Pancreatic Ductal/diagnosis
- Carcinoma, Pancreatic Ductal/genetics
- Carcinoma, Pancreatic Ductal/metabolism
- Carcinoma, Pancreatic Ductal/pathology
- Carcinoma, Pancreatic Ductal/surgery
- Carcinoma, Papillary/diagnosis
- Carcinoma, Papillary/genetics
- Carcinoma, Papillary/metabolism
- Carcinoma, Papillary/mortality
- Carcinoma, Papillary/pathology
- Carcinoma, Papillary/surgery
- Cholangiopancreatography, Endoscopic Retrograde
- Diagnostic Imaging
- Dilatation, Pathologic
- Disease Progression
- Endosonography
- Epithelium/pathology
- Humans
- Mucins/metabolism
- Neoplasm Invasiveness
- Pancreatic Ducts/pathology
- Survival Analysis
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Affiliation(s)
- Toms Augustin
- Department of Surgery, Guthrie-Robert Packer Hospital, One Guthrie Square, Sayre, PA 18840, USA
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Tajiri T, Inagaki T, Ohike N, Omatsu M, Kasugai H, Kunimura T, Shiokawa A, Mitsuya T, Morohoshi T. Intraductal oncocytic papillary carcinoma of the pancreas showing numerous hyaline globules in the lumen. Pathol Int 2010; 60:48-54. [PMID: 20055952 DOI: 10.1111/j.1440-1827.2009.02474.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Two cases of intraductal oncocytic papillary carcinoma (IOPC) treated surgically were analyzed on light microscopy and immunohistochemistry: that of a 61-year-old man and that of a 55-year-old man. There were no clinical symptoms in either case. Pancreatic abnormalities were discovered incidentally on CT. Various clinical examinations were carried out, and the preoperative diagnosis was intraductal papillary mucinous carcinoma (IPMC) in both cases. Surgery was performed. Macroscopic observation of tissue cross-sections indicated multilocular cystic mass containing polypoid lesions encapsulated by the dilated pancreatic duct. Histologically, the cyst walls were lined by columnar epithelial cells with complex papillary projections associated with oxyphilic cytoplasm, and they were strongly immunoreactive with anti-mitochondrial antibody in the cytoplasm. Electron microscopy showed numerous mitochondria in the cytoplasm. IOPC was diagnosed. Interestingly, amorphous hyaline globules were produced from the oxyphilic cells, which exhibited a bud-like appearance. The hyaline globules were not positive for mucin staining. No case of IPMC with hyaline globules has been reported to date. The production of hyaline globules may be related to oncocytic differentiation. It is suggested that hyaline globules should be regarded as a characteristic of IOPC.
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Affiliation(s)
- Takuma Tajiri
- Department of Diagnostic Pathology, Showa University Fujigaoka Hospital, Yokohama 227-8501, Japan.
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