Cystic tumours of the pancreas and PanIN
Jean-François FléjouService d’Anatomie Pathologique
Hôpital Saint-Antoine, AP-HP, UPMC - Paris 6, France
Cystic tumours of the pancreasClassically rare : - 5% of pancreatic tumours (?)- 5 to 10% of pancreatic cystic lesions (pseudocysts = 90%)
BUT : . More and more often fortuitously discovered (1% of abdominal CT scans)
. May be malignant or premalignant
--> Specific diagnostic and therapeutic issues
Epithelial cystic tumoursBenign
Intraducal papillary mucinous adenomaMucinous cystadenomaSerous cystadenoma (micro or macro-cystic)Benign cystic neuroendocrine tumourAcinar cell cystadenomaDermoid cystCystic hamartoma
BorderlineBorderline IPMTBorderline mucinous cystic tumourSolid pseudopapillary tumour
MalignantIPM carcinomaMucinous cystadenocarcinomaSerous cystadenocarcinomaCystic pancreatoblastomaCystic metastasisMalignant cystic neuroendocrine tumour
Classification of pancreatic cystic tumoursfrom Kosmahl et al 2004
Non tumorous epithelial cystsCongenital cystLymphoepithelial cystNon neoplastic mucinous cystObstructive cystEndométrial cyst
Non epithelial cystic tumoursBenign (lymphangiomas…)Malignant (sarcomas…)
Non tumorous non epithelial cystsPseudocystsParasitic cysts
Relative frequency of cystic neoplasms of the pancreas
Warshaw et al AFC 1997 Kosmahl et al
130 cases 527 cases 418 cases*
Mucinous cystic tumors 49% 44% 8%
Serous cystadenomas 31% 32% 10%
IPMT 11,5% 11% 18%
Solid pseudopapillary T 3% 4% 21%
Cystic endocrine tumor 1,5% 2% 4%
*includes pseudocysts
Cystic endocrine tumour
Clinical features
MEDIAN AGE FEMALE (%) SYMPTOMS HEAD (%)
Serous
cystadenoma
65 yrs 80 pain +
mass +/-
fortuitous +++
40
MCN 60 yrs 90 pain +++
mass ++
fortuitous +
20
IPMN 55 ans 40 acute
pancreatitis
+++
fortuite ++
60
Solid PP tumour 25 yrs 98 mass +
fortuitous +
Serous cystadenoma
• Often fortuitously discovered• Pancreatic head in women > 60 yrs• Typical microcystic appearence on imaging
• Benign : no surgery
Serous cystadenoma
• Typical epithelium
Serous cystic tumours
Atypical forms
• unilocular
• « malignant » : serous cystadenocarcinoma, no experience…
• Numerous synonyms (Frantz tumour …)
• Young female patients• Most often benign• Large, well limited• Suggestive histology,
characteristic IHC (β-catenin)• Histogenesis still debated
• 10% malignant cases, no markers: must be removed
Solid pseudopapillary tumour
Precancerous lesions of the pancreas
• Cancer of the pancreas = ductal adenocarcinoma• Poor prognosis, poorly recognised fisk factors, no
mass screening• Only 3 recognised precancerous lesions:
• Mucinous cystic neoplasms (MCN)• Intraductal papillary mucinous neoplasms (IPMN)• Pancreatic intraepithelial neoplasia (PanIN)
MCNs
• Female, body and tail• Independant from the ductal system• Uni or multicystic (cysts >2cm)• Various histogenetic hypotheses
• Premalignant : must be removed
MCNs2 components
• Epithelial with varied atypias: frombenign to malignant with invasion
• Mesenchymal « pseudo-ovarian »underlying stroma
IPMN - definition– Abnormal proliferation of the epithelium from a pancreatic
duct, secreting mucus, leading to duct dilation
– Adenoma, borderline, in situ carcinoma, invasive adenocarcinoma (WHO)
Hruban, 2004
• Papillomatosis• Villous adenoma• Papillary adenoma• Adenomatosis• Mucin hypersecreting tumor• Intraductal papillary tumor
• Mucinous ductal ectasia• Ductectatic mucinous
cystadenoma
Identical ductal cellIdentical risk of malignancy
WHO (1996): INTRADUCTAL PAPILLARY MUCINOUS TUMOR (IPMT)
Wirsung / secondary ducts
IPMN Pancreato-biliary Intestinal Oncocytic Gastric
MUC1
MUC2
MUC5AC
malignant SD +++
IPMNs : main questionsTo diagnose ?
EUS + punction: moderate sensitivity and specificity Benign or malignant ?
risk factors: main duct, major dilatation, mural noduleTopography and extension ?
frozen section +++Prognosis after resection ?
benign: excellent!malignant: better as ductal adenocarcinoma
Surveillance, no surgery ??small size, secondary ducts, asymptomatic
IPMN / PanIN
Hruban, 2004
Comparison PanIN - IPMN
PanIN IPMNClinical Dg No Yes
Visible on macroscopy. No YesMucin visible on macro No Yes
True papillae No YesMUC2 + No Yes
Loss SMAD4 30% PanIN3 RareAssoc. Mucinous AK No Yes
Hruban et al, Am J Surg Pathol 2004
• « Lesions » of small pancreatic ducts have been described for a long time: – Sommers Gastroenterology 1954 « pancreatic duct hyperplasia
and cancer »• Confusing terminology
– lesion, metaplasia, hyperplasia, dysplasia, neoplasia…• Significance still unclear
– Preneoplastic, paraneoplastic, nothing to see with cancer…• Pancreatic intraepithelial neoplasia « PanIN »
– Hruban et al, Am J Surg Pathol 2001 and 2004
Nal 1
32
Ductal extension, to distinguish from PanIN
IPMN
Molecular sequence // morphological sequence
PanIN – Diagnostic reproducibility (Hruban et al, Am J Surg Pathol 2001)
35 cases, before and after consensus between 8 experts• Before : 70 designations, 4 classifications• After :
– Consensus 5 pathologists 27/35 cases, 6 pathologists 17/35, 7 pathologists 10/35
– Kappa : 0.43 (PanIN-1), 0.14 (PanIN-2), 0.42 (PanIN-3)
Frequency of PanINPanIN PanIN-3
Normal pancreas
16% 0%
Pancreatitis 60% 4%
Cancer 82% 40%
Andea et al, Mod Pathol 2003
Very high frequency in asymptomatic patients with a strong family history of pancreatic cancer
Brune et al, Am J Surg Pathol 2006
J Hepatobiliary Pancreat Surg 2007
Mucinous cystic neoplasms: distinct pathway
Ponction
PSEUDOCYST SEROUS
CYSTADENO-
MA
MUCINOUS
CYSTADENO-
MA
MUCINOUS
CYSTADENO-
CARCINOMA
Amylase high low variable variable
Ca 19-9 variable low high high
CEA variable low high high
Ca 72-4 low low high high
Ca 15-3 low low low high
Mucins M1 variable low high high
Conclusions
• Cystic tumours of the pancreas are a specific subgroup ofpancreatic tumours
• They represent rare examples of pancreatic precancerouslesions (MCN & IPMN)
• IPMNs (macroscopic lesion) may be difficult todistinguish from PanIN (microscopic lesion)
• PanIN probably represents an important preneoplasticlesion of ductal adenocarcinoma of the pancreas
• It is important to diagnose and treat these lesions,especially in patients at high risk of pancreatic cancer
Diagnosis ?
Lymphoepithelial cyst
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