Pancreatic Cystic Lesions 원자력병원

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1 Pancreatic Cystic Lesions 원자력병원 박선 후

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3 Lines of cellular differentiation Ductal Acinar Undetermined Ductal adenocarcinoma Serous/ mucinous tumor Intraductal papillary mucinous neoplasm Acinar cell carcinoma Pancreatoblastoma Solid pseudopapillary neoplasm Endocrine Others Pancreatic endocrine neoplasm Lymphoepithelial cyst Mature cystic teratoma

4 Gross morphology 1824 : Becourt PJ Radiology Surgery Prevalence 1% up to 29% New entities

5 Benign non-neoplastic 5.2 % pseudocyst 3.1 % Enterogenous cyst 1.0% Squamoid cyst 1.0% Benign neoplastic 59.8 % Mucinous cystadenoma 12.4% Oligo/microcystic serous cystadenoma 20.6% IPMN, benign 25.8% Cystic schwannoma 1.0% Borderline neoplastic 17.5 % Mucinous cystic neoplasm 1.0% SPN 6.2% IPMN, borderline 10.3% Malignant neoplastic 17.5% IPMN, non-invasive 2.1% IPMN, invasive 14.4% Neuroendocrine cystic 1% TOTAL RESECTION : 470 cases, CYSTIC LESION : 97 cases (20.6 %) JOP. 2010; 11(4);

6 type cases benign malignancy IPMN 436 (41.0%) Mucinous cystic neoplasm 268 (25.2 %) SPN 195 (18.3 %) Serous cystic neoplasm 162 (15.2 %) Acinar cell cystic neoplasm 2 (0.2 %) 0 2 Mature teratoma 1 (0.1%) 1 0 Pancreas, 2008 ;37:

7 Non-neoplastic cyst with lining Non-neoplastic cyst without lining Cystic lesion True cyst Intraductal Degenerative

8 True cystic Serous cystic neoplasm (SCN) Mucinous cystic neoplasm (MCN) Intraductal Intraductal papillary mucinous neoplasm (IPMN) Intraductal oncocytic papillary neoplasm (IOPN) Degenerative Solid-pseudopapillary neoplasm (SPN) Ductal adenocarcinoma Acinar cell carcinoma Pancreatic endocrine neoplasm

9 Rare cases Acinar cell cystadenoma Acinar cell cystadenocarcinoma Intraductal tubular adenoma Intraductal tubular carcinoma Intraductal tubulopapillary neoplasm Intraductal acinar cell carcinoma Mucinous non-neoplastic cyst Lymphoepithelial cyst lymphangioma Congenital cyst Dermoid cyst Squamoid cyst of pancreatic duct Epidermoid cyst within intrapancreatic accessory spleen Mesenchymal neoplasm with cystic degeneration

10 True cystic Serous cystic neoplasm Microcystic Oligocystic Most common type of true cystic neoplasm Female: male = 3:1, mean age : 66 years Body and tail, central scar and calcification Relatively large mass (up to 25 cm) Malignant change : extremely rare or none (multicentricity) IHC (+) : LMWCK, EMA, MUC-6 (-) : CA19-9. CEA. MUC-1

11 Serous cystic neoplasm (SCN) = Serous cystic adenoma Microcystic Oligocystic (macrocystic) Male =female Mean age : 50 years Head of pancreas Indistinguishable from VHL-associated pancreatic cyst

12 True cystic Mucinous cystic neoplasm (MCN) Less common than SCN or IPMN male : female = 1: 20 (perimenopausal female) Mean age : 50 yrs Tale Large size : up to 35 cm Well demarcated multilocular lesion Not related to main duct Mucin-producing epithelium with scattered goblet cell, paneth cell, endocrine cells

13 Low to high grade cytologic atypia : CK7, 8, 18, 19, CEA, MUC5AC/ MUC2(scattered goblet cells) : MUC 1 (invasive carcinoma) Ovarian-like stroma : ER, PR, a-inhibin, calretinin, Melan-a, CD10 a/w invasive adenocarcinoma : less than 20% : typical ductal adenocarcinoma, (undifferentiated carcinoma with osteoclast-like giant cells, adenosquamous carcinoma, choriocarcinoma, sarcoma) Invasive carcinoma of type, cm, arising in association with MCNs ( cm)

14 MCNs Epithelial denudation fistula Obstruction/ dilatation Pseudocyst IPMNs Nonneoplastic mucinous lesions

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16 Pseudocyst 58세남자 DM, Alcoholic liver disease Epigastric pain, weight loss :3kg/3mos CA19-9 :151 u/ml (High)

17 Previous history No history Single cyst, nonloculated multiloculation No septation Thick-walled Wall<4mm Duct-cyst connection >65% Low-viscosity fluid with a raised amylase Pseudo cyst MCNs No duct-cyst connection high-viscosity fluid with low amylase Inflammatory cytology Malignant cytology Fluid tumor marker Fibrotic cystic wall Ovarian-like stroma Tumor cells Pancreatology, 2008 ;8:

18 Intraductal Intraductal papillary mucinous neoplasm (IPMN) Intraductal oncocytic papillary neoplasm (IOPN)

19 Main duct type combined type branch type Younger patient Low malignant potential

20 Intraductal papillary mucinous neoplasm (IPMN) Increased incidence 5% of resected pancreatic lesion 20% of cystic lesion Male > female (mean age : 68 yrs) Head > tail CK7, CK8, CK18, CK19, beta-catenin CEA, 19-9, MUC5AC K-ras mutation : 70%

21 Gastric foveolar Villous-intestinal Pancreatobiliary Invasion MUC1/MUC2 (-/-) MUC2/CDX2 (+) MUC1 (+) One-third Low-moderate grade dysplasia Moderate-high grade dysplasia High grade dysplasia Usually colloidal or conventional ductal types Colloidal adenocarcinoma Ductal adenocarcinoma

22 Combined cases IPMN-gastric type /pancreatobiliary-type IPMN-gastric type/ IPMN-intestinal type type Acta Histochem. Cytochem. 2003; 36:

23 overall 5-YSR : > 70% Recurrence non invasive residual dysplasia in resection margin or multifocality recurrent rate in invasive IPMN : 2/3, mainly liver metastasis patient with invasive carcinoma : poor prognosis 5YSR : 36% in some report Less than 3 cm branch type Younger patient Low malignant potential No mural nodule Asymptomatic No changes during follow-up HIGH GRADE IPMN < 5% W.A.T.C.H.F.U.L. WAIT

24 Differences in location and malignancy potential between IPMN-intestinal type and IPMN-gastric type Location of main lesion Intestinal type (n=27) Gastric type (n=36) main duct 25 (93%) 10 (28%) branch duct 2 (7%) 26 (72%) carcinomatous change 19 (70%) 5(14%) invasive carcinoma 8 (30%) 1 (3%)

25 Ann Surg Oncol 2010 (Epub ahead of print)

26 intestinal pancreatobiliary gastric Carcinoma/High grade 8/8 7/7 2/23 Low-moderate grade 21/23 Ann Surg Oncol 2010 (Epub ahead of print)

27 Pancreatic Cystic Fluid Concentration (ng/ml, ELISA) Serum level of MUC5AC (ng/ml, ELISA) Carcinoma /High grade Lowmoderate MUC2 MUC Ann Surg Oncol 2010 (Epub ahead of print)

28 IPMNs PanIN MCNs

29 Large :>1cm Macroscopic mass Radiologically detectable Visible mucin IPMNs Older age/ Male Head Intraductal/ multiple cyst Papillary structure Intestinal differentiation PanIN MCNs <0.5 cm Microscopic mass Incidental finding Younger /female Tail >>>> head Solitary cyst Ovarian-like stroma

30 Intraductal oncocytic papillary neoplasm (IOPN) 1996 Adsay et al. Macro: large, nodular, friable papilla Micro: tall, complex, arborizing pattern coexistence with gastric foveolar/ pancreatobiliary component Intraductal oncocytic papillary neoplasm with invasion J Hepatobiliary Pancreas Sci; 2010;17;

31 Gastric IPMN Basal weak MUC1/MUC2 (-) intestinal IPMN Negative MUC1 (-)/MUC2 (+) MUC6 in normal epithelium IOPN Positive MUC1/2 : variable PB IPMN Weak positive MUC1(+)/MUC2(-) Am J Surg 2010: 34:

32 IOPN (n=28) IPMN (literature review) Mean age (yr) Gender (% males) 14/28 (50%) 43-80% recurrence 2/21 (9.5%) 10.1 ~23% location Head : 19/28 (67.9%) Body : 3/28 (10.7 %) Tail : 3/28 (10.7%) others : 3/28 (10.7%) Involved duct Main duct : 10/12 (83.3%) Branch duct : 1/12 (8.3%) Accessory duct :1/12 Head : 65% (39-89%) Body : 24% (12-31%) Tail : 11% (5-21%) Main duct : 45% (9-92%) Branch duct : 44% (8-85%) Both type :24% (6-55%) Size (mean) 6 cm 3.2~4.0cm J Hepatobiliary Pancreas Sci; 2010;17;

33 IOPN (n=28) IPMN (literature review) High grade dysplasia 11/14 (78.6 %) % Invasive carcinoma 14/28 (50%) 10-67% Type of invasive carcinoma Tubular :7/10 Colloidal :0/10 Mixed/other : 3/10 Tubular :57-60% Colloidal :27-43% Mixed/other : 13% Vascular invasion 1/14 (7.1%) 13.3% LN metastasis 2/14 (14.3%) % K-ras mutation No mutation 20 ~ 61.5% MUC6 positive PB-type IPMN Mesothelin 84% 50% PB-IPMN CDX2 negative Intestinal IPMN J Hepatobiliary Pancreas Sci; 2010;17;

34 Rare cases Acinar cell cystadenoma Acinar cell cystadenocarcinoma Intraductal tubular adenoma Intraductal tubular carcinoma Intraductal tubulopapillary neoplasm Intraductal acinar cell carcinoma Mucinous non-neoplastic cyst Lymphoepithelial cyst lymphangioma Congenital cyst Dermoid cyst Squamoid cyst of pancreatic duct Epidermoid cyst within intrapancreatic accessory spleen Mesenchymal neoplasm with cystic degeneration

35 Intraductal tubular adenoma Macro : intraductal nodules involving main duct Micro : small tubular glands, similarity to pyloric gland MUC1 (-), MUC2 (+/-), MUC5AC (+), MUC6 (+) AJSP 2005: 29:

36 ITA (n=6) IPMN (n=111) Age (yrs) (63.5) (65) Sex M=F M>F (M; F= 64:48) Ductal dilatation Less than IPMN Localized to diffuse Location Head (4)> body (2) Head (66)>body(31)>tail Grossly visible mucus Less abundant or no Abundant Gross Polypoid/nodular Papillary/flat/diffuse Microscopy Closely packed tubular structure Papilla with tubular foci IHC phenotype Pyloric gland type only Gastric, intestinal, pancreaticobiliary Behavior benign Variable invasiveness no 18.9% AJSP 2005: 29:

37 Intraductal tubular carcinoma Macro : intraductal nodules involving main duct Micro : small tubular glands, back to back arrangement MUC1 (+), MUC2 (-), MUC5AC (-), MUC6 (+) Pancreas 2004: 29: Pancreas 2005: 30:

38 Pancreas 2004: 29: Pancreas 2005: 30:

39 Intraductal tubulopapillary neoplasms Macro : intraductal nodules without visible mucin Micro : tubulopapillary growth with scanty cytoplasmic mucin MUC1 (+), MUC2 (-), MUC5AC (-), MUC6 (+) no K-ras, B-raf mutation AJSP 2009: 33:

40 AJSP 2009: 33:

41 ITPN IPMN Gross Solid with no visible mucin Microscopy Tubulopapillary Papillary Cytology Cuboidal columnar with little mucin Cystic with secreted mucin Abundant mucin Atypia High-grade Low-high Necrosis Frequent Rare MUC2 Negative Occasional MUC5AC Negative Positive KRAS mutation no Frequent AJSP 2009: 33:

42 MUC1 MUC6 IMPN IOPN ITA ITC ITPN mucin abundant some scanty scanty scanty atypia Low-high high low high high K-ras mutation frequent no no MUC1 PB-type variable - variable + MUC2 Intestinal variable variable - - MUC5AC All variable MUC6 PB-type weak

43 Cystic/intraductal acinar cell carcinoma Very rare Smaller than ordinary ACC (mean :4.9 cm) Cystic/intraductal dilatation with nodule Papillary and/or papillocystic growth Nodular area : solid or acinar pattern Am J Surg 2007: 31:

44 case sex age location Size (cm) LN LIVER Endocrine component Survival 1 M 66 Tail yrs 2 F 31 Head M 54 Head F 82 Duodenal wall mos 5 M 65 Body mos (disease) 6 M 57 Head mos 7 F 60 head mos Comparing to ordinary Acinic cell carcinoma Relatively small size (4.9 cm vs. 10cm) Distinctive endocrine component (3 cases) Rarity of liver metastasis Better clinical outcome Am J Surg 2007: 31:

45 Rare cases Acinar cell cystadenoma Acinar cell cystadenocarcinoma Intraductal tubular adenoma Intraductal tubular carcinoma Intraductal tubulopapillary carcinoma Intraductal acinar cell carcinoma Mucinous non-neoplastic cyst Lymphoepithelial cyst lymphangioma Congenital cyst Dermoid cyst Squamoid cyst of pancreatic duct Epidermoid cyst within intrapancreatic accessory spleen Mesenchymal neoplasm with cystic degeneration

46 Acinar cell cystadenoma (Cystic acinar transformation) recently described lesion : 2000 Uncommon, usually incidental lesion unilocular or multilocular/ multicentricity trypsin, chymotrypsin, lipase (+) CK7 (+) : negative in normal acinar cells Trypsin J Pediatr Surg 2010: 45: e7-9

47 Acinar cell cystadenocarcinoma rare body and tail large multilocular cyst with solid area single layer of cuboidal or columnar cells acinar cells in solid nest DDx : Pancreatic endocrine neoplasm pancreatoblastoma Human Pathology 2004: 35:

48 Rare cases Acinar cell cystadenoma Acinar cell cystadenocarcinoma Intraductal tubular adenoma Intraductal tubular carcinoma Intraductal tubulopapillary carcinoma Intraductal acinar cell carcinoma Mucinous non-neoplastic cyst Lymphoepithelial cyst lymphangioma Congenital cyst Dermoid cyst Squamoid cyst of pancreatic duct Epidermoid cyst within intrapancreatic accessory spleen Mesenchymal neoplasm with cystic degeneration

49 Cystic lymphangioma Extremely rare, <1% of lymphangioma Female> male Affect all age group Palpable mass Epigastric pain World J Gastroenterol 2008; 14:

50 Degenerative Solid-pseudopapillary neoplasm (SPN) Ductal adenocarcinoma Acinar cell neoplasm Pancreatic endocrine neoplasm

51 Solid pseudopapillary neoplasm (SPN) Young woman 10~15% : metastasis to liver, peritoneum or rarely lymph node vimentin, a1-antitrypsin, CD56 (+) ER-b, PR (+) Synaptophysin, NSE (+) beta-catenin, CD10, c-kit, FLI-1 (+) Epithelial markers (-) Chromogranin (-) DDx : Cystic pancreatic endocrine neoplasm

52 Pancreatic endocrine neoplasm (PEN) mild cystic change is common Unilocular cyst or multilocular microcystic pattern

53 Thank you for your attention

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