Dr.

Anca Moldovan-Pop
V.D., 47 y, woman (12-21.12. 2011):
Admitted for :
 investigation of recurrent episodes of acute
pancreatitis

Personal history:
 episodes of intense epigastric pain radiating in the
upper left quadrant and in the back since 2004
 1-2 episodes/year
 constant hyperamylasuria (3560U/l)
 weight loss (8-10kg) and steatorrhea since 2011
 No history of diabetes
 Family history -insignificant
 Working-proper
 Behaviour-no alcohol intake, non-smoker, no medication

PHYSICAL EXAM
-underweight pacient (BMI=17,63kg/m²)

Local hospital investigations concluded a diagnosis of

chronic pancreatitis (CT-mass in the head of the pancreas,
Wirsung dilation, dilated intra- and extrahepatic bile ducts)
Clinical diagnosis

RECURRENT ACUTE PANCREATITIS

Causes of acute recurrent pancreatitis
1. TOXIC-METABOLIC
 Alcohol
 Hypertriglyceridemia, hypercalcemia, medications

2. MECHANICAL

 Choledocolithiasis
 Obstruction-ampullary (e.g., diverticulum, cyst, polyp, tumor, stenosis)
-pancreatic ductal (e.g., tumor, mucinous ductal neoplasia,
nonneoplastic stricture-chronic pancreatitis)
 Congenital malformations (e.g., annular pancreas)

3. MISCELLANOUS –hereditary pancreatitis

GASTROENTEROLOGY 2001;120:708–717
Lab tests
Imaging:abdominal ultrasound
 Dilated intrahepatic ducts.
 Non-hydropic gallbladder, no stones
 Mass in the pancreatic head that measures 36/35mm,
with hypoechoic elements (necrosis?), with
obstruction; dilation of Wirsung duct of 8mm with
edema of the wirsung mucosa.
 Local lymphadenopathy

Conclusion: mass in the head of the pancreas

(pseudocyst?)
IMAGING: EUS+FNA
 Endoscopically-papila with mucus.
 In the head of the pancreas-anechoic cystic lesion that
measures 2.5/1.8 cm with papilary projections, in the wall
 Istmic Wirsung is dilated with floating mass, echoic, inside,
with hipoechoic, thickened walls, measures 9mm (18mm if we
consider the wall);
 normal parenchyma cannot be identified
 Intimate contact of the lesion with the portal vein (no signs of
invasion)

 FNA-a few cells with mild nuclear atypia

Dg: Suspicion of mai- duct IPMN

EUS-film
IMAGING-CT
 Enlarged head of the pancreas (45mm) and marked changes regarding
structure with important dilation of the Wirsung duct that
measures 11 mm.
 There is a cystic lesion with the diameter of 23 mm
communicating with the Wirsung but also with the duodenum.
 Atrophy of the body and tail of the pancreas

 Moderate dilation of the intrahepatic bile ducts and of the common

bile duct (=9mm)
 The spleno-mesenteric confluent (after the split) has a diameter of
2mm-incomplete trombosis? Normal superior mesenteric artery.

Conclusion: Wirsung duct IPMN?

Spleno-mesenteric confluent incomplete trombosis?
Wirsung dilation in the body and tail of the
pancreas with moderate parenchymal atrophy

Cystic lesion in the head of the pancreas Markedly dilated pancreatic duct with
parenchymal atrophy.
Imaging :MRCP
 Important dilation of the Wirsung duct (11mm)
 In the head of the pancreas there are multiple cystic
lesions , with the biggest measuring 25mm
communicating with the Wirsung duct.
 Filiform aspect of the of the spleno-mesenteric
confluent
 Dilation of the intra- and extrahepatic bile ducts

Conclusion: Wirsung duct IPMN

Cystic lesion in the head of the pancreas (red arrow) communicating with an
uniform dilated Wirsung duct (yellow arrow) and the duodenum.
Differential diagnosis (by imaging)
1. CHRONIC PANCREATITIS

 calcifications in the Wirsung duct and parenchyma

 moniliform dilation of the Wirsung
 etiology

 Particular care!!! in patients who do not present typical

characteristics of the disease (IPMN?)
-namely age over 50 years,
-moderate alcohol intake
-non-smokers

Talamini G, Zamboni G, Salvia R, Capelli P, Sartori N, Casetti L, Bovo P, Vaona B Falconi M, Bassi C,
Scarpa A, Vantini I, Pederzoli P. Intraductal papillary mucinous neoplasms and chronic pancreatitis.
Pancreatology 2006; 6: 626-634
Differential diagnosis
-IPMN -misdiagnosed as chronic pancreatitis because:

 -symptoms of relapsing abdominal pain, acute pancreatitis, and

steatorrhea
 imaging findings of a dilated pancreatic duct, cystic lesions that are
frequently confused with pseudocysts

-IPMN may be responsible for pancreatic calcification (chronic partial

ductal obstruction by mucin plug)

Talamini G, Zamboni G, Salvia R, Capelli P, Sartori N, Casetti L, Bovo P, Vaona B, Falconi M, Bassi C, Scarpa A, Vantini I,
Pederzoli P. Intraductal papillary mucinous neoplasms and chronic pancreatitis. Pancreatology 2006; 6: 626-634

Intraductal papillary mucinous neoplasm (IPMN) and chronic pancreatitis: overlapping pathological entities? Two case reports. Petrou A, Papalambros A,
Brennan N, Prassas E, Margariti T, Bramis K, Rozemberg T, Papalambros E. Source Department of Hepatobilary Surgery, Churchill Hospital, Oxford, United
Kingdom.
Differential diagnosis
2. Mucinous cystic tumors:

 MCNs demonstrate ovarian-like stroma

 arise in the pancreatic tail or body, solitary

 do not communicate with the pancreatic duct.

Diagnosis (I)

1. MAIN-DUCT IPMN
2. COMMON BILE DUCT STENOSIS
3. SUSPICION OF SPLENO-MESENTERIC INVASION
Treatment
 SURGERY-total pancreatectomy (explained the life-
time diabetes mellitus with insulin)

 Refuse of the patient

Cystic lesions of the pancreas
 The prevalence of pancreatic cysts is 1.2%
(10% of cysts are neoplastic, 90%pseudocysts)

 1% of pancreatic neoplasms are cystic

Spinelli KS,et al. Ann Surg2004;239:651. Fernandez-del Castillo C,et al.SurgClinNorth Am1995;75:1001.
WarshawAL, et al. Ann Surg1990; 212:432
WHO Histological Classification of Neoplastic Pancreatic Cysts
1. Serous cystic tumors
 Serous cystadenoma
 Serous cystadenocarcinoma

2. Mucinous cystic tumors

 Mucinous cystadenoma
 Mucinous cystadenoma with moderate dysplasia
 Mucinous cystadenocarcinoma (noninfiltrating and infiltrating)

 Intraductal papillary mucinous adenoma (IPMA)

 Intraductal papillary mucinous neoplasm with moderate dysplasia
 Intraductal papillary mucinous carcinoma (noninfiltrating and infiltrating)

3. Solid pseudopapillary tumors

Kloppel G SE, Longnecker DS, Capella C, Sobin LH. Histological typing of tumors of the exocrine pancreas. World Health
Organization International Histological Classification of Tumors. Berlin: Springer Verlag, 1996
Malignant potential
1. Mucinous cystic neoplasm (MCN)
2. Intraductal-papillary mucinous neoplasia (IPMN)
3. Solid pseudopapillary tumors (SPT)

Usually benign:
Serous cystadenomas
Intraductal papillary-mucinous neoplasm of the pancreas (IPMN)

 IPMN is an epithelial neoplasm arising from the main pancreatic duct

or branch ducts, with varying degrees of duct dilatation.
-is a grossly visible,
-mucin-producing,
-predominantly papillary (or rarely flat )
-greater than 1 cm in diameter
 variety of cell types with a spectrum of cytologic and architectural
atypia.

 Lack ovarian-type stroma that characterizes mucinous cystic

neoplasms (dif.dg.)

Hruban, 2004;
IPMN
 term IPMN -officially adopted in 1996 by WHO

 5% of all cystic lesions

 Considered premalignant

 Men = Women
 Median age ~ 50 years
 75% symptomatic:
- weight loss, abdominal pain
-acute pancreatitis (25%)
-recurrent pancreatitis (20%)

Jimenez R and Fernandez‐del Castillo C. Tumors of The Pancreas. In: Feldman M et al. Sleisenger&Fordtran's Gastrointestinal and
Liver Disease. 9th Edition. Philadelphia: Saunders, 2010
Levy PJ., Clin Gastroenterol Hepatol2006;4:460–468.
IPMN-2 types
 Main-Duct IPMN

Can involve the entire duct

Dilation of duct >1cm strongly suggests main duct IPMN
57‐92% prevalence of cancer

 Branch- duct IPMN

Appear as small blebs on EUS

Pancreatic mucinous cyst communicating with main duct
without dilation
6‐46% prevalence of cancer

Tanaka M, Chari S, Adsay V, Fernandez‐del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Y

amao K, Matsuno S; International Association Of Pancreatology. International consensus guidelines
for management of intraductal papillary mucinousneoplasms and mucinous cystic neoplasms of the
pancreas. Pancreatology. 2006;6(1‐2):17‐32.
Malignancy in main-duct IPMNs (including the mixed type IPMN)

Reference (first Year Patients Malignant Invasive

author) published including malignancy%
CIS%
Kobari 1999 13 92 23
Terris 2000 30 57 37
Doi 2002 12 83 Not stated
Matsumoto 2003 27 63 Not stated
Choi 2003 34 85 Not stated
Sugyiama 2003 30 70 57
Sohn 2004 69 Not stated 45
Salvia 2004 140 60 42
Mean of all series 70 43
Clasiffication of IPMN (WHO 1996)

A.IPMN-adenoma
B.IPMN-borderline
C.IPMN-carcinoma in situ
D.IPMN-invasive carcinoma

adenoma

invasive cancer=5-6 years

Differential diagnosis

1. Chronic pancreatitis
2. Mucinous cystic tumors
Positive diagnosis

 CT (MDCT) and/or MRCP

 EUS
 ERCP
CT and MRCP
 Requires a dedicated pancreatic protocol technique

-tumor locations,
-relationship to surrounding structures
-lymph node involvement,
-metastatic disease

 shows dilation of the duct and atrophy of the parenchyma

 capable of detecting mural nodules

Waters JA, Schmidt CM, Pinchot JW et al. CT vs MRCP: Optimal classification of IPMN type and extent J Gastrointest Surg
2008;12:101–109.
EUS
 Identifies dilation of the pancreatic
duct in the absence of chronic pancreatitis
or obstructing mass

 Detection - mural nodules,

- internal septa,
- solid masses

 Lymph node and vascular invasion

 Endoscopic visualisation of mucus extruding

from patulous ampulla (“fish-mouth”)

 FNA-for cytological analysis, determination of tumor markers concentration,

molecular diagnosis
Prediction of malignancy by EUS
1. main-duct IPMN
2. dilated main pancreatic duct > 10 mm in size
3. mural nodules

 EUS is useful for diagnosing

IPMN, particularly for predicting
malignancy.

Sugiyama M, Atomi Y, Saito M. Intraductal papillary tumors of the pancreas: evaluation with endoscopic
ultrasonography. Gastrointest Endosc 1998; 48:164.)
 EUS-differentiating between benign and malignant IPMN

 Accuracy 86%
 Sensitivity 77%
 Specificity 89%

Diameter of mural Malignant Benign

nodules (n=9) (n=17)
</=5mm 1 7
6-10mm 1 9
11-15mm 2 1
>/=15mm 5 0

Hiroaki K, Ioshiharo C. et al, Intraductal-papillary mucinous tumors of the pancreas. Differential diagnosis between
benign and malignant tumors by endoscopic ultrasonography. The American Journal of Gastroenetrology
(2001) 96; 1429-1434
ERCP
 Patulous ampulla of Vater
extruding mucus (20% –50%)

 Main-duct IMPN may show diffuse main duct dilation,

mucinous filling defects, and a papillary tumor in
main duct

Advantage: -obtain cytology

- therapeutic maneuvers
 Pancreatoscopy

-study of 60 patients -sensitivity=95% in IPMN correct identification

Yamao K, Ohashi K, Nakamura T, et al. Efficacy of peroral pancreatoscopy in the diagnosis of pancreatic diseases. Gastrointest
Endosc 2003; 57:205.

-the presence of fish egg-like, villous, and prominent mucosal

protrusions had a sensitivity of 68 % and a specificity of 87 %for
malignancy
Hara T, Yamaguchi T, Ishihara T, et al. Diagnosis and patient management of intraductal papillary-mucinous tumor of the
pancreas by using peroral pancreatoscopy and intraductal ultrasonography. Gastroenterology 2002; 122:34
Serum markers
 CA 19-9 and CEA

-differentiation of invasive from noninvasive IPMN

Fritz S, Hackert T, Hinz U, et al. Role of serum carbohydrate antigen 19-9 and carcinoembryonic antigen in
distinguishing between benign and invasive intraductal papillary mucinous neoplasm of the pancreas.
Br J Surg 2011; 98:104.
Treatment
 Prediction of malignancy:
-main-duct IPMN (60% of resected IPMN harbor cancer)
-age (6,4 y diff between be-ma)
-symptoms ( jaundice and/or worsening of diabetes)

 29% of patients with malignant main-duct IPMNs were

asymptomatic
 reliance on symptoms could not exclude malignancy

(Salvia R, Fernández-del Castillo C, Bassi C Thayer SP, Falconi M, Mantovani W, Pederzol P, Warshaw AL: Main duct
intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and longterm survival
following resection. Ann Surg 2004; 239: 678–687.
Sendai consensus guideline
Most if not all benign lesions of main-duct IPMN
may progress to invasive cancer (60-92%)
Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS: Mucinous cystic neoplasm of lowgrade
malignant potential) of the pancreas: a clinicopathologic study of 130 cases. Am J Surg
Pathol 1999; 23: 1–16.

Resection of main duct-IPMN is recommended for

all patients who are good surgical candidates with
reasonable life expectancy .
International guideline, Pancreatology 2006
Sahani, DV, et al. Clinical Gastroenterology and Hepatology 2009;7:259-269
Treatment-surgery

partial/total pancreatectomy?
Surgery
 The most common operation is pancreaticoduodenectomy (70%)
because most tumors are in the head of the pancreas.

 frozen sections of the resection margins during surgery can determine

tumor extent and the need for further surgical resection,

 a negative surgical margin does not preclude the presence of neoplasia

in the remnant pancreas

Paye F, Sauvanet A, Terris B, et al. Intraductal papillary mucinous tumors of the pancreas: pancreatic resections guided by
preoperative morphological assessment and intraoperative frozen section examination. Surgery 2000; 127:536.

Salvia R, Fernández-del Castillo C, Bassi C Thayer SP, Falconi M, Mantovani W, Pederzol P, Warshaw AL: Main duct
intraductal papillary mucinous neoplasms of the pancreas
Surgery
 if multiple lesions (multifocality/”field defects”) or
 concerning radiologic or endoscopic features, total
pancreatectomy may be considered

 needs weighing carefully the risks of malignancy

versus the issues that arise in apancreatic patients.
International Guideline, Pancreatology 2006
 Survival after surgery
 5-year survival of non-invasive IPMN up to 80%

 5-year survival of invasive IPMN=36-60% (vs 9-20% for

ductal adenocarcinoma); because lower rates of:
- advanced T stage,
- nodal metastasis,
- positive resection margins
- perineural and vascular invasion

 if present, survival outcomes= similar to those of

pancreatic ductal adenocarcinoma.
Waters JA, Schnelldorfer T, Aguilar-Saavedra JR, et al. Survival after resection for invasive intraductal papillary mucinous neoplasm
and for pancreatic adenocarcinoma: J Am Coll Surg 2011; 213:275.
Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD. Intraductal papillary mucinous neoplasms of
Survival
Recurrence
 rare after resection of noninvasive tumors

 recurrent disease localized to the pancreas benefits from complete

pancreatectomy

Predictors of worse outcome:

 Elevated bilirubin
 Invasive IPMN (12‐65% recurrence at 3 years)
 Lymph node metastases
 Vascular invasion

Salvia R,et al. Clinical Ann Surg2004;239:678. D'AngelicaM,et al. Ann Surg2004;239:400.
Evolution of the case
Returns in 1.03.2012 (after 2 and ½ month) with
cholangitis

 Fever (39 degrees Celsius) for 2 weeks

 Pain in the upper right quadrant radiating in the back
 Jaundice for 3 days
 Vomiting
Lab tests
CT (comparative)
 Hepatic abcess segment 6,7,8
 More important distension of intra and extrahepatic bile
ducts
 Increasing mass of the head of the pancreas (5/6cm) on
account of Wirsung dilation and cystic lesions
 The Wirsung duct measures 19.5 mm
 Liquid near duodenum, gallbladder, space under the live,
between the intestinal loops (malignant etiology?)
 Proximal portal vein and the spleno-mesenteric confluent
appears filiform, into the mass
ERCP with stenting
 Shows duodenal invasion
 Mucus protruding from the papila
 Stenting of the common bile duct

Conclusion: mucinous tumor

of the pancreas with duodenal
and common bile duct invasion
ERCP-film
Treatment
I.V. liquids
Antiemetics
Antibiotics
Clinical evolution
 Persistent jaundice
 Vomiting (1-2/day after
meals, without nausea)
Evolution
 Abdominal ultrasound shows a functional stent with
aerobilia

 A duodenal stent shoul be placed

Final diagnosis
1. MAIN-DUCT IPMN WITH DUODENAL INVASION
2. COMMON BILE DUCT STENOSIS
3. HEPATIC ABCESSES
4. ACUTE CHOLANGITIS
5. SPLENO-MESENTERIC INVASION
6. PERITONEAL METASTASIS?
Main duct IPMN

Branch -duct IPMN

Va multumesc!
Consensus nomenclature and criteria for classification of features of four types of
intraductal papillary-mucinous neoplasm of the pancreas

 Gastric mild
atypia

 Intestinal
(coloid carcinoma)

 Pancreato-biliary
(tubular carcinoma)

 Oncocytic severe
atypia