ipmn and other intraductal tumors - pancreatic cancer europe · 2018. 3. 15. · tajiri et al,...
TRANSCRIPT
![Page 1: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/1.jpg)
IPMN and other intraductal
tumors
Irene Esposito
Pancreatic pathology: Of mice and men
Madrid, December 4-6th 2014
![Page 2: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/2.jpg)
Cystic lesions of the pancreas
Nonneoplastic Neoplastic
Pseudocyst
Mucinous cystic neoplasm
Serous cystic tumors
Intraductal neoplasm (IPMN, ITPN)
Solid pseudopapillary neoplasm
Mucinous nonneoplastic cyst
Lymphoepithelial cystRetention cyst Acinar cell cystadenocarcinoma
Cystic endocrine neoplasm
Cystic ductal adenocarcinomas
Cystic mesenchymal tumor
Acinar cell cystadenoma
Mod. from Farrell & Fernández- del Castillo, Gastroenterology 2013
![Page 3: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/3.jpg)
Cystic lesions of the pancreas
Nonneoplastic Neoplastic
Pseudocyst
Mucinous cystic neoplasm
Serous cystic tumors
Intraductal Neoplasm (IPMN, ITPN)
Solid pseudopapillary neoplasm
Mucinous non-neoplastic cyst
Lymphoepithelial cystRetention cyst Acinar cell cystadenocarcinoma
Cystic neuroendocrine neoplasm
Cystic ductal adenocarcinomas
Cystic mesenchymal tumor
Acinar cell cystadenoma
95%
![Page 4: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/4.jpg)
Intraductal papillary-mucinous neoplasms 61%
Serous cystic neoplasms 16.2%
Mucinous cystic neoplasms 15.1%
Solid pseudopapillary neoplasms 3.5%
Pseudocysts 1.1%Retention cysts 1.1%
unpublished
788 resections, 86 cystic tumors (11%)Munich, Rechts der Isar, 2007-2014
![Page 5: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/5.jpg)
Main duct type
Intestinal type
Pancreatobiliary type
Oncocytic type
Intraductal papillary mucinousneoplasms (IPMN)
Branch duct type
Gastric type
![Page 6: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/6.jpg)
pancreatobiliary intestinal gastric
PB INT Gas Onc
Muc1 ++ - - +
Muc2 - ++ - -
Muc5 + + ++ ++ +
Muc6 + - - ++
CDX2 - ++ - -
oncocytic
WHO 2010
![Page 7: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/7.jpg)
Benign observation possible
Low-grade lesion
resection, different outcomes & follow-up
High-grade lesion
Malignant potential & treatment
![Page 8: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/8.jpg)
20% of all IPMNs
Sex: equal age: 40 - 80 y (mean 68)
Localization 80% in the head region
Invasiveness in 10 - 50 % of the cases
Prognosis: more favorable than PDAC
IPMN – Main duct- Intestinal type
Lüttges et al, Am J Surg Path 2001Adsay et al, Am J Surg Path 2002 and 2004Furukawa et al, Virchows Arch 2005
![Page 9: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/9.jpg)
in situ ca
invasive ca(mucinous „colloid“ type)
![Page 10: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/10.jpg)
Adsay et al., Am J Surg Path 2001
PDAC
IPMN – Survival
colloid
ordinary PDAC
![Page 11: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/11.jpg)
Muc2 CDX2
Diagnosis:Intestinal-Type IPMNMain ductLow-grade
![Page 12: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/12.jpg)
Malignant potential
Benign Low-grade High-grade Treatment
Intestinal IPMN
Resection
![Page 13: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/13.jpg)
8-10% of all IPMN
Sex equal age : 40 - 80 y (mean 68)
Localization 80% in the head region
Carcinoma in situ> 80%; invasive >50%
Type of Ca classical PDAC
Prognosis similar to PDAC
IPMN – Main duct- Pancreatobiliary type
Lüttges et al. Am J Surg Path 2001Adsay et al Am J Surg Path 2002 and 2004Furukawa et al Virchows Arch 2005Mino-Kenudson et al, Gut 2010
![Page 14: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/14.jpg)
MUC1
invasive ca(classical tubular type)
![Page 15: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/15.jpg)
Malignant potentialBenign Low-grade High-grade Treatment
Intestinal IPMN
Resection
Pancreato-biliary IPMN
Resection
![Page 16: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/16.jpg)
IPMN non invasive65%
No recurrence93%
Recurrence7%
benign 3%malignant 4%
IPMN with invasive ca35%
No recurrence35%
Recurrence65 %
metastatic/local
Positive resection margin with high-grade IPMNrecurrence in almost 100%
Positive resection margin with low-grade IPMNrecurrence in 0 – 52%
Chari et al, Gastroenterology 2002
IPMN main duct – follow up
![Page 17: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/17.jpg)
70 % of all IPMN
Sex: equal age 50 –70
branch duct(s) – uncinate process, 39% multifocal
rarely invasive, but if – tubular type carcinoma (classical
PDAC)
prognosis: favorable (invasive component in 11%, 9-27%)
resection indicated in <20% patients (Sendai criteria)
IPMN – side branch– gastric type
Takada et al, HepatoGastroenterology 1998Terris et al, Am J Surg Pathol 2000Furukawa et al, Virchows Arch 2005Ruben Rodriguez et al, Gastroenterology 2007Del Castillo & Adsay, Gastroenterology 2011
![Page 18: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/18.jpg)
Benign Low-grade High-grade Treatment
Intestinal IPMN Resection
Pancreato-biliary IPMN
Resection
Gastric IPMN According tomod. Sendai‘scriteria
Malignant potential
![Page 19: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/19.jpg)
IPMN non invasive89%
No recurrence96%
Recurrence4%
benign 100%
IPMN withinvasive ca
11%
No recurrence59%
Recurrence41 %
distant
Crippa et al, ClinGastroenterol Hepatol 2010
BD-IPMN – follow up
N=159, recurrence in 13 (8%)
![Page 20: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/20.jpg)
Furukawa et al, Gut 2011
Morphology as predictor of survival
gastric
PB
ONCINT
![Page 21: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/21.jpg)
Molecular changes in IPMN
48 cases, 60% MD, 6% BD, 34% combined75% INT, 12.5 GAS, 6% PB, 6% ONC
57% with invasive ca62% colloid38% tubular
Non-invasive IPMN: 6% LG, 35% MG, 58% HG
Amato et al, J Pathol 2014
![Page 22: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/22.jpg)
Molecular changes in IPMN
GNAS (75%), codon 201KRAS (46%), codon 12 (mostly), 14, 22, 61
RNF43 (14%)TP53 (10%), exons 5 & 6BRAF (6%) exon 15
GNAS and/or KRAS: 87%
Amato et al, J Pathol 2014
GNAS: intestinal & gastric type KRAS: gastric > intestinalRNF43: intestinal & pancreatobiliaryTP53: intestinal & pancreatobiliary (high-grade)
![Page 23: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/23.jpg)
Intraductal tubulopapillary neoplasm(ITPN)
„An intraductal, grossly visible epithelial neoplasm withhigh-grade dysplasia and ductal differentiation and withoutovert production of mucin“
Suda et al, Am J Gastroenterol 1996Esposito et al, Virchows Arch 2004Tajiri et al, Pancreas 2005Yamaguchi et al, Am J Surg Pathol 2009
M=F35-84 years (mean 56)Unspecific symptoms, no biomarkersImaging: like IPMN50% head, 35% all pancreas, 15% tailMean size 6 cm (0.8-15 cm)
![Page 24: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/24.jpg)
Tightly packed tubulesUsually high-grade dysplasia, invasive ca in 40%
ITPN
![Page 25: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/25.jpg)
Ductal cytokeratins, Muc1, Muc5 negKras wt (NRAS, GNAS)p16: del of exon 1p53: not overexpressedSmad4/Dpc4: lossbeta-catenin: mut. codon 34
Beta-catenin Smad4
Esposito et al, Virchows Arch 2004
![Page 26: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/26.jpg)
Schlitter, Esposito et al, in preparation
Molecular pathology of ITPN
![Page 27: IPMN and other intraductal tumors - Pancreatic Cancer Europe · 2018. 3. 15. · Tajiri et al, Pancreas 2005 Yamaguchi et al, Am J Surg Pathol 2009 M=F 35-84 years (mean 56) Unspecific](https://reader035.vdocuments.mx/reader035/viewer/2022071000/5fbc562e034fd614550b931e/html5/thumbnails/27.jpg)
Summary
IPMN are the most common cystic tumors of the pancreas in surgical series
Different histological subtypes with different biological behavior exist
Subtyping is achieved by combination of morphology and IHC and is clinically relevant
The molecular events leading to the development of IPMN differs from those of PDAC